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Cui X, Situ J, Tang T, Li Z, Chen D, Ho SSF, Chung HL, Wong TC, Liang Y, Deng C, Su Y, Cai H, Lo SKF, Huang S, Zeng S, Zhang L, Chen Y, Wu S, Shun EHK, Chew NFS, Tsoi JYH, Lo KHY, Xing F, Cheng VCC, Yuen KY, Yin F, Chan JFW, Sridhar S. Prevalence of Rocahepevirus ratti (rat hepatitis E virus) in humans and rats in China. JHEP Rep 2025; 7:101370. [PMID: 40342633 PMCID: PMC12060442 DOI: 10.1016/j.jhepr.2025.101370] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/22/2024] [Revised: 02/19/2025] [Accepted: 02/21/2025] [Indexed: 05/11/2025] Open
Abstract
Background & Aims Rocahepevirus ratti (rat hepatitis E virus; rHEV) is a ubiquitous pathogen of rats that has recently emerged as a cause of hepatitis in humans. Although several rHEV cases have been detected worldwide, the extent of human exposure to this hepatitis agent is still poorly defined. We conducted a multicenter surveillance study in China examining rHEV exposures in demographically diverse human populations from a One Health perspective. Methods In this multicenter cross-sectional study, we used fully validated rHEV IgG enzymatic immunoassays and reverse transcription PCR in 1,199 individuals with (n = 655) or without hepatitis (n = 544) recruited from three centers in China (Hainan, Hong Kong, and Shenzhen). The patient population included both urban and rural populations. Characteristics of infected individuals and phylogenetic links with rat epizootics were described. Results rHEV IgG seroprevalence was higher in the rural Hainan cohort (15/229, 6.6%) compared with Shenzhen (9/427, 2.1%) and Hong Kong cohorts (2/543, 0.4%) (p <0.0001). This difference persisted on multivariable logistic regression with an adjusted odds ratio of 20.52 (95% CI: 13.86-30.39). rHEV exposure was also associated with increasing age and environmental rodent exposure. We observed rHEV viraemia in two hepatitis patients (2/655; 0.3%) in Hainan and Hong Kong with hepatitis B and renal transplantation, respectively. The latter developed chronic hepatitis E. 19/509 (3.7%) rats captured in Hainan harbored rHEV. Both human rHEV isolates were phylogenetically related to rodent-derived rHEV strains circulating in Hainan and Hong Kong, respectively. Conclusions Humans are intermittently exposed to rHEV, especially in rural settings with rodent exposure. Overt hepatitis occurs in individuals with liver disease or immunosuppression. Spillover strains are related to epizootics in rodents offering opportunities for targeted disinfestation. Impact and implications Building on our previous work finding that Rocahepevirus ratti (rHEV) is a novel cause of sporadic viral hepatitis in humans, we studied rHEV exposures in humans from various epidemiological settings. We found intermittent exposure to rat hepatitis E in individuals living in both urban and rural settings with a markedly higher seroprevalence in the latter. Spillover viremic infections in individuals with underlying liver disease or immunosuppression were closely linked to epizootic rHEV strains circulating in rodents. Physicians and diagnostic laboratories should incorporate rHEV testing in algorithms for viral hepatitis while policymakers should consider rHEV surveillance in rodents to guide disinfestation efforts.
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Affiliation(s)
- Xiuji Cui
- Hainan Medical University-The University of Hong Kong Joint Laboratory of Tropical Infectious Diseases, Key Laboratory of Tropical Translational Medicine of Ministry of Education, Academician Workstation of Hainan Province, School of Basic Medicine and Life Sciences, Hainan Medical University, Haikou, Hainan, China
| | - Jianwen Situ
- Department of Microbiology, Queen Mary Hospital, Pokfulam, Hong Kong Special Administrative Region of China
| | - Ting Tang
- Hainan Medical University-The University of Hong Kong Joint Laboratory of Tropical Infectious Diseases, Key Laboratory of Tropical Translational Medicine of Ministry of Education, Academician Workstation of Hainan Province, School of Basic Medicine and Life Sciences, Hainan Medical University, Haikou, Hainan, China
| | - Zhiyu Li
- Department of Microbiology, Queen Mary Hospital, Pokfulam, Hong Kong Special Administrative Region of China
| | - Dongzhui Chen
- The First Affiliated Hospital of Hainan Medical University, Hainan Medical University, Haikou, Hainan, China
| | - Stanley Siu-Fung Ho
- Department of Microbiology, Queen Mary Hospital, Pokfulam, Hong Kong Special Administrative Region of China
| | - Hiu-Laam Chung
- Department of Microbiology, Queen Mary Hospital, Pokfulam, Hong Kong Special Administrative Region of China
| | - Tsz-Chung Wong
- Department of Microbiology, Queen Mary Hospital, Pokfulam, Hong Kong Special Administrative Region of China
| | - Yonghao Liang
- Department of Microbiology, Queen Mary Hospital, Pokfulam, Hong Kong Special Administrative Region of China
| | - Chaowen Deng
- Department of Infectious Diseases and Microbiology, The University of Hong Kong-Shenzhen Hospital, Shenzhen, Guangdong, China
| | - Yongxian Su
- Department of Infectious Diseases and Microbiology, The University of Hong Kong-Shenzhen Hospital, Shenzhen, Guangdong, China
| | - Huijun Cai
- Department of Infectious Diseases and Microbiology, The University of Hong Kong-Shenzhen Hospital, Shenzhen, Guangdong, China
| | - Simon Kam-Fai Lo
- Department of Infectious Diseases and Microbiology, The University of Hong Kong-Shenzhen Hospital, Shenzhen, Guangdong, China
| | - Shiyao Huang
- Department of Infectious Diseases and Microbiology, The University of Hong Kong-Shenzhen Hospital, Shenzhen, Guangdong, China
| | - Sheng Zeng
- Department of Infectious Diseases and Microbiology, The University of Hong Kong-Shenzhen Hospital, Shenzhen, Guangdong, China
| | - Liyuan Zhang
- Department of Infectious Disease, the Second Affiliated Hospital of Hainan Medical University, Haikou, Hainan, China
| | - Yunchun Chen
- Department of Laboratory Medicine, Haikou Hospital of Traditional Chinese Medicine, Haikou, China
| | - Shusheng Wu
- Department of Microbiology, Queen Mary Hospital, Pokfulam, Hong Kong Special Administrative Region of China
| | - Estie Hon-Kiu Shun
- Centre for Virology, Vaccinology and Therapeutics, Hong Kong Science and Technology Park, Hong Kong Special Administrative Region of China
| | - Nicholas Foo-Siong Chew
- Department of Microbiology, Queen Mary Hospital, Pokfulam, Hong Kong Special Administrative Region of China
| | - James Yiu-Hung Tsoi
- Department of Microbiology, Queen Mary Hospital, Pokfulam, Hong Kong Special Administrative Region of China
| | - Kelvin Hon-Yin Lo
- Department of Microbiology, Queen Mary Hospital, Pokfulam, Hong Kong Special Administrative Region of China
| | - Fanfan Xing
- Department of Infectious Diseases and Microbiology, The University of Hong Kong-Shenzhen Hospital, Shenzhen, Guangdong, China
| | - Vincent Chi-Chung Cheng
- Department of Microbiology, Queen Mary Hospital, Pokfulam, Hong Kong Special Administrative Region of China
| | - Kwok-Yung Yuen
- Department of Microbiology, Queen Mary Hospital, Pokfulam, Hong Kong Special Administrative Region of China
- Centre for Virology, Vaccinology and Therapeutics, Hong Kong Science and Technology Park, Hong Kong Special Administrative Region of China
- State Key Laboratory of Emerging Infectious Diseases, Carol Yu Centre for Infection, Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region of China
- Guangzhou Laboratory, Guangzhou, Guangdong Province, China
- Guangdong Provincial Key Laboratory of Virology, Institute of Medical Microbiology, Jinan University, Guangzhou, China
- Pandemic Research Alliance Unit at The University of Hong Kong, The University of Hong Kong, Hong Kong Special Administrative Region of China
| | - Feifei Yin
- Hainan Medical University-The University of Hong Kong Joint Laboratory of Tropical Infectious Diseases, Key Laboratory of Tropical Translational Medicine of Ministry of Education, Academician Workstation of Hainan Province, School of Basic Medicine and Life Sciences, Hainan Medical University, Haikou, Hainan, China
| | - Jasper Fuk-Woo Chan
- Hainan Medical University-The University of Hong Kong Joint Laboratory of Tropical Infectious Diseases, Key Laboratory of Tropical Translational Medicine of Ministry of Education, Academician Workstation of Hainan Province, School of Basic Medicine and Life Sciences, Hainan Medical University, Haikou, Hainan, China
- Department of Microbiology, Queen Mary Hospital, Pokfulam, Hong Kong Special Administrative Region of China
- Centre for Virology, Vaccinology and Therapeutics, Hong Kong Science and Technology Park, Hong Kong Special Administrative Region of China
- State Key Laboratory of Emerging Infectious Diseases, Carol Yu Centre for Infection, Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region of China
- Pandemic Research Alliance Unit at The University of Hong Kong, The University of Hong Kong, Hong Kong Special Administrative Region of China
| | - Siddharth Sridhar
- Department of Microbiology, Queen Mary Hospital, Pokfulam, Hong Kong Special Administrative Region of China
- Pandemic Research Alliance Unit at The University of Hong Kong, The University of Hong Kong, Hong Kong Special Administrative Region of China
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Chen Z, Wang L, Zhang Y, Li G, Yin J, Fan J, Liu T, Wu H, Huang Y, Huang W, Liu D, Zheng X, Zang X, Huang X, Song L, Wen S, Li J, Ying D, Fang M, Wang Y, Wu T, Sridhar S, Zhang J, Xia N, Wang L, Lu Y, Zheng Z. Substantial spillover burden of rat hepatitis E virus in humans. Nat Commun 2025; 16:4038. [PMID: 40301345 PMCID: PMC12041280 DOI: 10.1038/s41467-025-59345-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2024] [Accepted: 04/18/2025] [Indexed: 05/01/2025] Open
Abstract
The emergence of Rocahepevirus ratti genotype 1 (rat hepatitis E virus; rat HEV) in humans presents an unprecedented threat; however, the risk of rat HEV transmission to humans is not well understood. Here, we report the "Distinguishing Antibody Response Elicitation (DARE)" method, which distinguishes exposure to rat HEV. We use four study sets from China for large-scale population analysis: set 1 (hospital visit) and set 3 (ALT abnormality) from Yunnan province, a biodiversity hotspot, and set 2 (received physical examination) and set 4 (ALT abnormality) from Jiangsu province, a non-hotspot control region. rat HEV exposure risk is significantly higher in Yunnan, with 21.97% (190 of 865) in set 1 and 13.97% (70 of 501) in set 3, compared to 0.75% (9 of 1196) in Jiangsu's set 2. Six spillover infections for rat HEV are identified in set 1, with one case of abnormal ALT. The rat-1d strains carried by rats are closely related to those human infections. Our study reveals the substantial spillover burden posed by rat HEV in biodiversity hotspots and highlights the utility of DARE method for proactive surveillance of public health emergencies.
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Affiliation(s)
- Zihao Chen
- State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, Department of Laboratory Medicine, School of Public Health, Xiamen University, Xiamen, Fujian, PR China
- National Institute of Diagnostics and Vaccine Development in Infectious Diseases, National Innovation Platform for Industry-Education Integration in Vaccine Research, NMPA Key Laboratory for Research and Evaluation of Infectious Disease Diagnostic Technology, School of Public Health, School of Life Sciences, Xiamen University, Xiamen, Fujian, PR China
| | - Lifeng Wang
- Menghai County People's Hospital, Menghai, Yunnan, PR China
| | - Yongde Zhang
- Menghai County Center for Disease Control and Prevention, Menghai, Yunnan, PR China
| | - Guanghui Li
- State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, Department of Laboratory Medicine, School of Public Health, Xiamen University, Xiamen, Fujian, PR China
- National Institute of Diagnostics and Vaccine Development in Infectious Diseases, National Innovation Platform for Industry-Education Integration in Vaccine Research, NMPA Key Laboratory for Research and Evaluation of Infectious Disease Diagnostic Technology, School of Public Health, School of Life Sciences, Xiamen University, Xiamen, Fujian, PR China
| | - Jiaxiang Yin
- Department of Epidemiology, School of Public Health, Dali University, Dali, Yunnan, PR China
| | - Jingyan Fan
- State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, Department of Laboratory Medicine, School of Public Health, Xiamen University, Xiamen, Fujian, PR China
- National Institute of Diagnostics and Vaccine Development in Infectious Diseases, National Innovation Platform for Industry-Education Integration in Vaccine Research, NMPA Key Laboratory for Research and Evaluation of Infectious Disease Diagnostic Technology, School of Public Health, School of Life Sciences, Xiamen University, Xiamen, Fujian, PR China
| | - Tianxu Liu
- Department of Microbiology and Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, PR China
| | - Han Wu
- Department of Epidemiology, Ministry of Education Key Laboratory of Public Health Safety (Fudan University), School of Public Health, Fudan University, Shanghai, PR China
| | - Yue Huang
- State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, Department of Laboratory Medicine, School of Public Health, Xiamen University, Xiamen, Fujian, PR China
- National Institute of Diagnostics and Vaccine Development in Infectious Diseases, National Innovation Platform for Industry-Education Integration in Vaccine Research, NMPA Key Laboratory for Research and Evaluation of Infectious Disease Diagnostic Technology, School of Public Health, School of Life Sciences, Xiamen University, Xiamen, Fujian, PR China
| | - Wenhui Huang
- State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, Department of Laboratory Medicine, School of Public Health, Xiamen University, Xiamen, Fujian, PR China
- National Institute of Diagnostics and Vaccine Development in Infectious Diseases, National Innovation Platform for Industry-Education Integration in Vaccine Research, NMPA Key Laboratory for Research and Evaluation of Infectious Disease Diagnostic Technology, School of Public Health, School of Life Sciences, Xiamen University, Xiamen, Fujian, PR China
| | - Donglin Liu
- Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, Jiangsu, PR China
| | - Xiaoxiang Zheng
- Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, Jiangsu, PR China
| | - Xia Zang
- Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, Jiangsu, PR China
| | - Xingcheng Huang
- State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, Department of Laboratory Medicine, School of Public Health, Xiamen University, Xiamen, Fujian, PR China
- National Institute of Diagnostics and Vaccine Development in Infectious Diseases, National Innovation Platform for Industry-Education Integration in Vaccine Research, NMPA Key Laboratory for Research and Evaluation of Infectious Disease Diagnostic Technology, School of Public Health, School of Life Sciences, Xiamen University, Xiamen, Fujian, PR China
| | - Liuwei Song
- Xiamen Innodx Biotechnology Co., Ltd, Xiamen, Fujian, PR China
| | - Shunhua Wen
- Xiamen Innodx Biotechnology Co., Ltd, Xiamen, Fujian, PR China
| | - Jiayu Li
- Xiamen Innodx Biotechnology Co., Ltd, Xiamen, Fujian, PR China
| | - Dong Ying
- State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, Department of Laboratory Medicine, School of Public Health, Xiamen University, Xiamen, Fujian, PR China
- National Institute of Diagnostics and Vaccine Development in Infectious Diseases, National Innovation Platform for Industry-Education Integration in Vaccine Research, NMPA Key Laboratory for Research and Evaluation of Infectious Disease Diagnostic Technology, School of Public Health, School of Life Sciences, Xiamen University, Xiamen, Fujian, PR China
| | - Mujin Fang
- State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, Department of Laboratory Medicine, School of Public Health, Xiamen University, Xiamen, Fujian, PR China
- National Institute of Diagnostics and Vaccine Development in Infectious Diseases, National Innovation Platform for Industry-Education Integration in Vaccine Research, NMPA Key Laboratory for Research and Evaluation of Infectious Disease Diagnostic Technology, School of Public Health, School of Life Sciences, Xiamen University, Xiamen, Fujian, PR China
| | - Yingbin Wang
- State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, Department of Laboratory Medicine, School of Public Health, Xiamen University, Xiamen, Fujian, PR China
- National Institute of Diagnostics and Vaccine Development in Infectious Diseases, National Innovation Platform for Industry-Education Integration in Vaccine Research, NMPA Key Laboratory for Research and Evaluation of Infectious Disease Diagnostic Technology, School of Public Health, School of Life Sciences, Xiamen University, Xiamen, Fujian, PR China
| | - Ting Wu
- State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, Department of Laboratory Medicine, School of Public Health, Xiamen University, Xiamen, Fujian, PR China
- National Institute of Diagnostics and Vaccine Development in Infectious Diseases, National Innovation Platform for Industry-Education Integration in Vaccine Research, NMPA Key Laboratory for Research and Evaluation of Infectious Disease Diagnostic Technology, School of Public Health, School of Life Sciences, Xiamen University, Xiamen, Fujian, PR China
| | - Siddharth Sridhar
- Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, PR China
- Centre for Virology, Vaccinology and Therapeutics, Health@InnoHK, Hong Kong, PR China
- State Key Laboratory of Emerging Infectious Diseases and Carol Yu Centre for Infection, The University of Hong Kong, Hong Kong, PR China
| | - Jun Zhang
- State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, Department of Laboratory Medicine, School of Public Health, Xiamen University, Xiamen, Fujian, PR China
- National Institute of Diagnostics and Vaccine Development in Infectious Diseases, National Innovation Platform for Industry-Education Integration in Vaccine Research, NMPA Key Laboratory for Research and Evaluation of Infectious Disease Diagnostic Technology, School of Public Health, School of Life Sciences, Xiamen University, Xiamen, Fujian, PR China
| | - Ningshao Xia
- State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, Department of Laboratory Medicine, School of Public Health, Xiamen University, Xiamen, Fujian, PR China.
- National Institute of Diagnostics and Vaccine Development in Infectious Diseases, National Innovation Platform for Industry-Education Integration in Vaccine Research, NMPA Key Laboratory for Research and Evaluation of Infectious Disease Diagnostic Technology, School of Public Health, School of Life Sciences, Xiamen University, Xiamen, Fujian, PR China.
- Research Unit of Frontier Technology of Structural Vaccinology, Chinese Academy of Medical Sciences, Xiamen, Fujian, PR China.
| | - Lin Wang
- Department of Microbiology and Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, PR China.
| | - Yihan Lu
- Department of Epidemiology, Ministry of Education Key Laboratory of Public Health Safety (Fudan University), School of Public Health, Fudan University, Shanghai, PR China.
| | - Zizheng Zheng
- State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, Department of Laboratory Medicine, School of Public Health, Xiamen University, Xiamen, Fujian, PR China.
- National Institute of Diagnostics and Vaccine Development in Infectious Diseases, National Innovation Platform for Industry-Education Integration in Vaccine Research, NMPA Key Laboratory for Research and Evaluation of Infectious Disease Diagnostic Technology, School of Public Health, School of Life Sciences, Xiamen University, Xiamen, Fujian, PR China.
- Department of Clinical Laboratory, Xiang'an Hospital of Xiamen University, Xiamen University, Xiamen, Fujian, PR China.
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Shun EHK, Situ J, Tsoi JYH, Wu S, Cai J, Lo KHY, Chew NFS, Li Z, Poon RWS, Teng JLL, Cheng VCC, Yuen KY, Sridhar S. Rat hepatitis E virus (Rocahepevirus ratti) exposure in cats and dogs, Hong Kong. Emerg Microbes Infect 2024; 13:2337671. [PMID: 38551320 PMCID: PMC11018080 DOI: 10.1080/22221751.2024.2337671] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2023] [Accepted: 03/27/2024] [Indexed: 04/06/2024]
Abstract
Hepatitis E virus (HEV) variants infecting humans belong to two species: Paslahepevirus balayani (bHEV) and Rocahepevirus ratti (rat hepatitis E virus; rHEV). R. ratti is a ubiquitous rodent pathogen that has recently been recognized to cause hepatitis in humans. Transmission routes of rHEV from rats to humans are currently unknown. In this study, we examined rHEV exposure in cats and dogs to determine if they are potential reservoirs of this emerging human pathogen. Virus-like particle-based IgG enzymatic immunoassays (EIAs) capable of differentiating rHEV & bHEV antibody profiles and rHEV-specific real-time RT-PCR assays were used for this purpose. The EIAs could detect bHEV and rHEV patient-derived IgG spiked in dog and cat sera. Sera from 751 companion dogs and 130 companion cats in Hong Kong were tested with these IgG enzymatic immunoassays (EIAs). Overall, 13/751 (1.7%) dogs and 5/130 (3.8%) cats were sero-reactive to HEV. 9/751 (1.2%) dogs and 2/130 (1.5%) cats tested positive for rHEV IgG, which was further confirmed by rHEV immunoblots. Most rHEV-seropositive animals were from areas in or adjacent to districts reporting human rHEV infection. Neither 881 companion animals nor 652 stray animals carried rHEV RNA in serum or rectal swabs. Therefore, we could not confirm a role for cats and dogs in transmitting rHEV to humans. Further work is required to understand the reasons for low-level seropositivity in these animals.
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Affiliation(s)
- Estie Hon-Kiu Shun
- Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, People’s Republic of China
| | - Jianwen Situ
- Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, People’s Republic of China
| | - James Yiu-Hung Tsoi
- Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, People’s Republic of China
| | - Shusheng Wu
- Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, People’s Republic of China
| | - Jianpiao Cai
- Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, People’s Republic of China
| | - Kelvin Hon-Yin Lo
- Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, People’s Republic of China
| | - Nicholas Foo-Siong Chew
- Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, People’s Republic of China
| | - Zhiyu Li
- Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, People’s Republic of China
| | - Rosana Wing-Shan Poon
- Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, People’s Republic of China
| | - Jade Lee-Lee Teng
- Faculty of Dentistry, The University of Hong Kong, Hong Kong, People’s Republic of China
| | - Vincent Chi-Chung Cheng
- Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, People’s Republic of China
| | - Kwok-Yung Yuen
- Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, People’s Republic of China
- Centre for Virology, Vaccinology and Therapeutics, Health@InnoHK, The University of Hong Kong, Hong Kong, People’s Republic of China
- State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Pokfulam, People’s Republic of China
- Carol Yu Centre for Infection, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, People’s Republic of China
| | - Siddharth Sridhar
- Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, People’s Republic of China
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Casares-Jimenez M, Rivero-Juarez A, Lopez-Lopez P, Montes ML, Navarro-Soler R, Peraire J, Espinosa N, Alemán-Valls MR, Garcia-Garcia T, Caballero-Gomez J, Corona-Mata D, Perez-Valero I, Ulrich RG, Rivero A. Rat hepatitis E virus ( Rocahepevirus ratti) in people living with HIV. Emerg Microbes Infect 2024; 13:2295389. [PMID: 38095070 PMCID: PMC10763910 DOI: 10.1080/22221751.2023.2295389] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2023] [Accepted: 12/12/2023] [Indexed: 12/31/2023]
Abstract
Rat hepatitis E virus (ratHEV; species Rocahepevirus ratti) is considered a newly emerging cause of acute hepatitis of zoonotic origin. ratHEV infection of people living with HIV (PLWH) might portend a worse, as with hepatitis E virus (HEV; species Paslahepevirus balayani), and consequently this group may constitute a high-risk population. We aimed to evaluate the prevalence of ratHEV by measuring viral RNA and specific IgG antibodies in a large Spanish cohort of PLWH. Multicentre study conducted in Spain evaluating PLWHIV included in the Spanish AIDS Research Network (CoRIS). Patients were evaluated for ratHEV infection using PCR at baseline and anti-ratHEV IgG by dot blot analysis to evaluate exposure to ratHEV strains. Patients with detectable ratHEV RNA were followed-up to evaluate persistence of viremia and IgG seroconversion. Eight-hundred and forty-two individuals were tested. A total of 9 individuals showed specific IgG antibodies against ratHEV, supposing a prevalence of 1.1 (95% CI; 0.5%-2.1%). Of these, only one was reactive to HEV IgG antibodies by ELISA. One sample was positive for ratHEV RNA (prevalence of infection: 0.1%; 95% CI: 0.08%-0.7%). The case was a man who had sex with men exhibiting a slightly increased alanine transaminase level (49 IU/L) as only biochemical alteration. In the follow-up, the patients showed undetectable ratHEV RNA and seroconversion to specific ratHEV IgG antibodies. Our study shows that ratHEV is geographical broadly distributed in Spain, representing a potential zoonotic threat.
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Affiliation(s)
- María Casares-Jimenez
- Infectious Diseases Unit, Reina Sofia University Hospital, Maimonides Instituto for Biomedical Research (IMIBIC), University of Cordoba (UCO), Cordoba, Spain
| | - Antonio Rivero-Juarez
- Infectious Diseases Unit, Reina Sofia University Hospital, Maimonides Instituto for Biomedical Research (IMIBIC), University of Cordoba (UCO), Cordoba, Spain
- CIBERINFEC, ISCIII – CIBER on Infectious Diseases, Carlos III Health Institute, Madrid, Spain
| | - Pedro Lopez-Lopez
- Infectious Diseases Unit, Reina Sofia University Hospital, Maimonides Instituto for Biomedical Research (IMIBIC), University of Cordoba (UCO), Cordoba, Spain
- CIBERINFEC, ISCIII – CIBER on Infectious Diseases, Carlos III Health Institute, Madrid, Spain
| | - María Luisa Montes
- CIBERINFEC, ISCIII – CIBER on Infectious Diseases, Carlos III Health Institute, Madrid, Spain
- HIV Unit, Internal Medicine Service, La Paz University Hospital, IdiPAZ, Madrid, Spain
| | | | - Joaquín Peraire
- CIBERINFEC, ISCIII – CIBER on Infectious Diseases, Carlos III Health Institute, Madrid, Spain
- Infectious Diseases Unit, Joan XXIII University Hospital, IISPV, Rovira i Virgili University, Tarragona, Spain
| | - Nuria Espinosa
- Infectious Diseases and Clinical Microbiology Unit, Virgen del Rocío University Hospital, CSIC, IbIS, University of Seville, Seville, Spain
| | | | - Tránsito Garcia-Garcia
- Immunogenomic and Molecular Pathogenesis, Zoonoses and Emerging diseases Unit (ENZOEM), Genetic Department, University of Cordoba, Cordoba, Spain
| | - Javier Caballero-Gomez
- Infectious Diseases Unit, Reina Sofia University Hospital, Maimonides Instituto for Biomedical Research (IMIBIC), University of Cordoba (UCO), Cordoba, Spain
- CIBERINFEC, ISCIII – CIBER on Infectious Diseases, Carlos III Health Institute, Madrid, Spain
- Animal Health Unit, Zoonoses and Emerging diseases Unit (ENZOEM), University of Cordoba, Cordoba, Spain
| | - Diana Corona-Mata
- Infectious Diseases Unit, Reina Sofia University Hospital, Maimonides Instituto for Biomedical Research (IMIBIC), University of Cordoba (UCO), Cordoba, Spain
- CIBERINFEC, ISCIII – CIBER on Infectious Diseases, Carlos III Health Institute, Madrid, Spain
| | - Ignacio Perez-Valero
- Infectious Diseases Unit, Reina Sofia University Hospital, Maimonides Instituto for Biomedical Research (IMIBIC), University of Cordoba (UCO), Cordoba, Spain
- CIBERINFEC, ISCIII – CIBER on Infectious Diseases, Carlos III Health Institute, Madrid, Spain
| | - Rainer G. Ulrich
- Institute of Novel and Emerging Infectious Diseases, Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, Greifswald-Insel Riems, Germany
- German Centre for Infection Research (DZIF), partner site Hamburg-Lübeck-Borstel-Riems, Greifswald-Insel Riems, Germany
| | - Antonio Rivero
- Infectious Diseases Unit, Reina Sofia University Hospital, Maimonides Instituto for Biomedical Research (IMIBIC), University of Cordoba (UCO), Cordoba, Spain
- CIBERINFEC, ISCIII – CIBER on Infectious Diseases, Carlos III Health Institute, Madrid, Spain
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Casares-Jimenez M, Corona-Mata D, Garcia-Garcia T, Manchado-Lopez L, Rios-Muñoz L, de Guia-Castro M, Lopez-Lopez P, Caceres-Anillo D, Camacho A, Caballero-Gomez J, Perez-Valero I, Gallo-Marin M, Perez AB, Ulrich RG, Rivero-Juarez A, Rivero A. Serological and molecular survey of rat hepatitis E virus ( Rocahepevirus ratti) in drug users. Emerg Microbes Infect 2024; 13:2396865. [PMID: 39193634 PMCID: PMC11376293 DOI: 10.1080/22221751.2024.2396865] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2024] [Revised: 08/02/2024] [Accepted: 08/21/2024] [Indexed: 08/29/2024]
Abstract
ABSTRACTRat hepatitis E virus (ratHEV) is an emerging cause of acute hepatitis of zoonotic origin. Since seroprevalence studies are scarce, at-risk groups are almost unknown. Because blood-borne infections frequently occur in people with drug use, who are particularly vulnerable to infection due to lack of housing and homelessness, this population constitutes a priority in which ratHEV infection should be evaluated. Therefore, the aim of this study was to evaluate the ratHEV seroprevalence and RNA detection rate in drug users as a potential at-risk population. We designed a retrospective study involving individuals that attended drug rehabilitation centres. Exposure to ratHEV was assessed by specific antibody detection using ELISA and dot blot (DB) assay and the presence of active infection by ratHEV RNA detection using RT-qPCR. Three-hundred and forty-one individuals were included, the most of them being men (67.7%) with an average age of 45 years. A total of 17 individuals showed specific IgG antibodies against ratHEV (4.6%; 95% CI; 3.1%-7.9%). One case of active ratHEV infection was identified (0.3%; 95% CI: 0.1%-1.8%). This was a 57-year-old homeless woman with limited financial resources, who had active cocaine and heroin use via parenteral route. In conclusion, we identified a potential exposure to ratHEV among drug users. Targeted studies in drug users with proper control groups are necessary to evaluate high-risk populations and transmission routes more accurately.
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Affiliation(s)
- Maria Casares-Jimenez
- Grupo de Virología Clínica y Zoonosis, Unidad de Enfermedades Infecciosas, Hospital Universitario Reina Sofía, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Universidad de Córdoba (UCO), Córdoba, España
- CIBERINFEC, ISCIII-CIBER de Enfermedades Infecciosas, Instituto de Salud Carlos III. Majadahonda, Madrid, España
| | - Diana Corona-Mata
- Grupo de Virología Clínica y Zoonosis, Unidad de Enfermedades Infecciosas, Hospital Universitario Reina Sofía, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Universidad de Córdoba (UCO), Córdoba, España
- CIBERINFEC, ISCIII-CIBER de Enfermedades Infecciosas, Instituto de Salud Carlos III. Majadahonda, Madrid, España
| | - Transito Garcia-Garcia
- Immunogenomic and Molecular Pathogenesis, Zoonoses and Emerging Diseases Unit (ENZOEM), Genetic Department, University of Cordoba, Cordoba, Spain
| | - Leticia Manchado-Lopez
- Unidad de Drogas y Adicciones-CPD (UDA-CPD), Instituto Provincial Bienestar Social, Diputación Córdoba, Córdoba, España
| | - Lucia Rios-Muñoz
- Grupo de Virología Clínica y Zoonosis, Unidad de Enfermedades Infecciosas, Hospital Universitario Reina Sofía, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Universidad de Córdoba (UCO), Córdoba, España
| | - Maria de Guia-Castro
- Unidad de Drogas y Adicciones-CPD (UDA-CPD), Instituto Provincial Bienestar Social, Diputación Córdoba, Córdoba, España
| | - Pedro Lopez-Lopez
- Grupo de Virología Clínica y Zoonosis, Unidad de Enfermedades Infecciosas, Hospital Universitario Reina Sofía, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Universidad de Córdoba (UCO), Córdoba, España
- CIBERINFEC, ISCIII-CIBER de Enfermedades Infecciosas, Instituto de Salud Carlos III. Majadahonda, Madrid, España
| | - David Caceres-Anillo
- Unidad de Drogas y Adicciones-CPD (UDA-CPD), Instituto Provincial Bienestar Social, Diputación Córdoba, Córdoba, España
| | - Angela Camacho
- Grupo de Virología Clínica y Zoonosis, Unidad de Enfermedades Infecciosas, Hospital Universitario Reina Sofía, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Universidad de Córdoba (UCO), Córdoba, España
- CIBERINFEC, ISCIII-CIBER de Enfermedades Infecciosas, Instituto de Salud Carlos III. Majadahonda, Madrid, España
| | - Javier Caballero-Gomez
- Grupo de Virología Clínica y Zoonosis, Unidad de Enfermedades Infecciosas, Hospital Universitario Reina Sofía, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Universidad de Córdoba (UCO), Córdoba, España
- CIBERINFEC, ISCIII-CIBER de Enfermedades Infecciosas, Instituto de Salud Carlos III. Majadahonda, Madrid, España
- Departamento de Sanidad Animal, Grupo de Investigación en Sanidad Animal y Zoonosis (GISAZ), UIC Zoonosis y Enfermedades Emergentes (ENZOEM), Universidad de Córdoba, Córdoba, España
| | - Ignacio Perez-Valero
- Grupo de Virología Clínica y Zoonosis, Unidad de Enfermedades Infecciosas, Hospital Universitario Reina Sofía, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Universidad de Córdoba (UCO), Córdoba, España
- CIBERINFEC, ISCIII-CIBER de Enfermedades Infecciosas, Instituto de Salud Carlos III. Majadahonda, Madrid, España
| | - Marina Gallo-Marin
- Grupo de Virología Clínica y Zoonosis, Unidad de Enfermedades Infecciosas, Hospital Universitario Reina Sofía, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Universidad de Córdoba (UCO), Córdoba, España
| | - Ana Belen Perez
- CIBERINFEC, ISCIII-CIBER de Enfermedades Infecciosas, Instituto de Salud Carlos III. Majadahonda, Madrid, España
- Unidad de Microbiología, Hospital Universitario Reina Sofía, Córdoba, España
| | - Rainer G Ulrich
- Institute of Novel and Emerging Infectious Diseases, Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, Greifswald-Insel Riems, Germany
- German Centre for Infection Research (DZIF), Partner Site Hamburg-Lübeck-Borstel-Riems, Greifswald-Insel Riems, Germany
| | - Antonio Rivero-Juarez
- Grupo de Virología Clínica y Zoonosis, Unidad de Enfermedades Infecciosas, Hospital Universitario Reina Sofía, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Universidad de Córdoba (UCO), Córdoba, España
- CIBERINFEC, ISCIII-CIBER de Enfermedades Infecciosas, Instituto de Salud Carlos III. Majadahonda, Madrid, España
| | - Antonio Rivero
- Grupo de Virología Clínica y Zoonosis, Unidad de Enfermedades Infecciosas, Hospital Universitario Reina Sofía, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Universidad de Córdoba (UCO), Córdoba, España
- CIBERINFEC, ISCIII-CIBER de Enfermedades Infecciosas, Instituto de Salud Carlos III. Majadahonda, Madrid, España
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Castagna F, Liguori G, Lombardi R, Bava R, Costagliola A, Giordano A, Quintiliani M, Giacomini D, Albergo F, Gigliotti A, Lupia C, Ceniti C, Tilocca B, Palma E, Roncada P, Britti D. Hepatitis E and Potential Public Health Implications from a One-Health Perspective: Special Focus on the European Wild Boar ( Sus scrofa). Pathogens 2024; 13:840. [PMID: 39452712 PMCID: PMC11510200 DOI: 10.3390/pathogens13100840] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2024] [Revised: 09/23/2024] [Accepted: 09/27/2024] [Indexed: 10/26/2024] Open
Abstract
The hepatitis E virus (HEV) has become increasingly important in recent years in terms of risk for public health, as the main causative agent of acute viral hepatitis. It is a foodborne disease transmitted to humans through the consumption of contaminated water or contaminated food. Human-to-human transmission is sporadic and is linked to transfusions or transplants. The main reservoirs of the hepatitis E virus are domestic pigs and wild boars, although, compared to pigs, wild boars represent a lesser source of risk since their population is smaller and the consumption of derived products is more limited. These peculiarities often make the role of the wild boar reservoir in the spread of the disease underestimated. As a public health problem that involves several animal species and humans, the management of the disease requires an interdisciplinary approach, and the concept of "One Health" must be addressed. In this direction, the present review intends to analyze viral hepatitis E, with a particular focus on wild boar. For this purpose, literature data have been collected from different scientific search engines: PubMed, MEDLINE, and Google scholar, and several keywords such as "HEV epidemiology", "Extrahepatic manifestations of Hepatitis E", and "HEV infection control measures", among others, have been used. In the first part, the manuscript provides general information on the disease, such as epidemiology, transmission methods, clinical manifestations and implications on public health. In the second part, it addresses in more detail the role of wild boar as a reservoir and the implications related to the virus epidemiology. The document will be useful to all those who intend to analyze this infectious disease from a "One-Health" perspective.
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Affiliation(s)
- Fabio Castagna
- Department of Health Sciences, University of Catanzaro Magna Græcia, 88100 Catanzaro, Italy; (F.C.); (B.T.); (E.P.); (P.R.); (D.B.)
- Mediterranean Ethnobotanical Conservatory, 88054 Catanzaro, Italy;
| | - Giovanna Liguori
- Local Health Authority, ASL, 71121 Foggia, Italy; (G.L.); (R.L.)
| | - Renato Lombardi
- Local Health Authority, ASL, 71121 Foggia, Italy; (G.L.); (R.L.)
| | - Roberto Bava
- Department of Health Sciences, University of Catanzaro Magna Græcia, 88100 Catanzaro, Italy; (F.C.); (B.T.); (E.P.); (P.R.); (D.B.)
| | - Anna Costagliola
- Department of Veterinary Medicine and Animal Productions, University of Napoli Federico II, 80100 Naples, Italy;
| | - Antonio Giordano
- Sbarro Institute for Cancer Research and Molecular Medicine, Center for Biotechnology, Department of Biology, College of Science and Technology, Temple University, 1900 N 12th Street, Philadelphia, PA 19122, USA;
- Department of Medical Biotechnology, University of Siena, 10100 Siena, Italy
| | | | | | - Francesco Albergo
- Department of Management, Finance and Technology, University LUM Giuseppe Degennaro, 70100 Casamassima, Italy;
| | - Andrea Gigliotti
- Interregional Park of Sasso Simone and Simoncello, 61021 Carpegna, Italy;
| | - Carmine Lupia
- Mediterranean Ethnobotanical Conservatory, 88054 Catanzaro, Italy;
| | - Carlotta Ceniti
- ASL Napoli 3 SUD, Department of Prevention, 80053 Castellammare di Stabia, Italy;
| | - Bruno Tilocca
- Department of Health Sciences, University of Catanzaro Magna Græcia, 88100 Catanzaro, Italy; (F.C.); (B.T.); (E.P.); (P.R.); (D.B.)
| | - Ernesto Palma
- Department of Health Sciences, University of Catanzaro Magna Græcia, 88100 Catanzaro, Italy; (F.C.); (B.T.); (E.P.); (P.R.); (D.B.)
| | - Paola Roncada
- Department of Health Sciences, University of Catanzaro Magna Græcia, 88100 Catanzaro, Italy; (F.C.); (B.T.); (E.P.); (P.R.); (D.B.)
| | - Domenico Britti
- Department of Health Sciences, University of Catanzaro Magna Græcia, 88100 Catanzaro, Italy; (F.C.); (B.T.); (E.P.); (P.R.); (D.B.)
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7
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De Sabato L, Monini M, Galuppi R, Dini FM, Ianiro G, Vaccari G, Ostanello F, Di Bartolo I. Investigating the Hepatitis E Virus (HEV) Diversity in Rat Reservoirs from Northern Italy. Pathogens 2024; 13:633. [PMID: 39204234 PMCID: PMC11357196 DOI: 10.3390/pathogens13080633] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2024] [Revised: 07/23/2024] [Accepted: 07/24/2024] [Indexed: 09/03/2024] Open
Abstract
Hepatitis E virus belonging to the Rocahepevirus ratti species, genotype HEV-C1, has been extensively reported in rats in Europe, Asia and North America. Recently, human cases of hepatitis associated with HEV-C1 infection have been reported, but the zoonotic nature of rat-HEV remains controversial. The transmission route of rat-HEV is unidentified and requires further investigation. The HEV strains of the Paslahepevirus balayani species, belonging to the same Hepeviridae family, and including the zoonotic genotype HEV-3 usually found in pigs, have also sporadically been identified in rats. We sampled 115 rats (liver, lung, feces) between 2020 and 2023 in Northeast Italy and the HEV detection was carried out by using Reverse Transcription PCR. HEV RNA was detected in 3/115 (2.6%) rats who tested positive for HEV-C1 strains in paired lung, intestinal contents and liver samples. Overall, none tested positive for the Paslahepevirus balayani strains. In conclusion, our results confirm the presence of HEV-rat in Italy with a prevalence similar to previous studies but show that there is a wide heterogeneity of strains in circulation. The detection of HEV-C1 genotype of Rocahepevirus ratti species in some human cases of acute hepatitis suggests that HEV-C1 may be an underestimated source of human infections. This finding, with the geographically widespread detection of HEV-C1 in rats, raises questions about the role of rats as hosts for both HEV-C1 and HEV-3 and the possibility of zoonotic transmission.
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Affiliation(s)
- Luca De Sabato
- Department of Food Safety, Nutrition and Veterinary Public Health, Istituto Superiore di Sanità, Viale Regina Elena, 299, 00161 Rome, Italy; (L.D.S.); (G.I.); (G.V.); (I.D.B.)
| | - Marina Monini
- Department of Food Safety, Nutrition and Veterinary Public Health, Istituto Superiore di Sanità, Viale Regina Elena, 299, 00161 Rome, Italy; (L.D.S.); (G.I.); (G.V.); (I.D.B.)
| | - Roberta Galuppi
- Department of Veterinary Medical Sciences, University of Bologna, Via Tolara di Sopra, 50, Ozzano dell’Emilia, 40064 Bologna, Italy; (R.G.); (F.M.D.); (F.O.)
| | - Filippo Maria Dini
- Department of Veterinary Medical Sciences, University of Bologna, Via Tolara di Sopra, 50, Ozzano dell’Emilia, 40064 Bologna, Italy; (R.G.); (F.M.D.); (F.O.)
| | - Giovanni Ianiro
- Department of Food Safety, Nutrition and Veterinary Public Health, Istituto Superiore di Sanità, Viale Regina Elena, 299, 00161 Rome, Italy; (L.D.S.); (G.I.); (G.V.); (I.D.B.)
| | - Gabriele Vaccari
- Department of Food Safety, Nutrition and Veterinary Public Health, Istituto Superiore di Sanità, Viale Regina Elena, 299, 00161 Rome, Italy; (L.D.S.); (G.I.); (G.V.); (I.D.B.)
| | - Fabio Ostanello
- Department of Veterinary Medical Sciences, University of Bologna, Via Tolara di Sopra, 50, Ozzano dell’Emilia, 40064 Bologna, Italy; (R.G.); (F.M.D.); (F.O.)
| | - Ilaria Di Bartolo
- Department of Food Safety, Nutrition and Veterinary Public Health, Istituto Superiore di Sanità, Viale Regina Elena, 299, 00161 Rome, Italy; (L.D.S.); (G.I.); (G.V.); (I.D.B.)
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8
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Molini U, Franzo G, de Villiers L, van Zyl L, de Villiers M, Khaiseb S, Busch F, Knauf S, Dietze K, Eiden M. Serological survey on Hepatitis E virus in Namibian dogs, cats, horses, and donkeys. Front Vet Sci 2024; 11:1422001. [PMID: 39091395 PMCID: PMC11292797 DOI: 10.3389/fvets.2024.1422001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2024] [Accepted: 07/04/2024] [Indexed: 08/04/2024] Open
Abstract
The present study investigated the seropositivity rate of Hepatitis E virus (HEV) in domestic and working animals in Namibia, which included dogs, cats, horses, and donkeys. HEV poses a growing threat as a significant cause of human hepatitis globally and has several genotypes of varying zoonotic potential. As epidemiological data on the seroprevalence of HEV in Namibia is scarce, a serosurvey was conducted on archived serum samples of 374 dogs, 238 cats, 98 horses, and 60 donkeys collected between 2018 and 2022 from different regions, to assess the potential of these animals as sources of HEV infection. The findings revealed that 10.43% (n = 39/374) canine and 5.88% (n = 14/238) feline samples tested positive for HEV antibodies, whereas no seropositivity was detected in horses and donkeys. The study further examined the risk factors associated with HEV seropositivity, including animal sex, age, and geographical region, and noted a higher prevalence in dogs living in areas with intensive pig farming. Although there is no direct evidence indicating that these animals served as major reservoirs for HEV transmission to humans, the study underscores the importance of preventive measures to minimize contact exposure with pets considering the potential zoonotic risk, especially for susceptible risk groups. Further research is needed to explore the zoonotic potential of domestic animals and the epidemiological links between animal and human HEV transmissions in Namibia.
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Affiliation(s)
- Umberto Molini
- School of Veterinary Medicine, Faculty of Health Sciences and Veterinary Medicine, University of Namibia, Windhoek, Namibia
- Central Veterinary Laboratory (CVL), Windhoek, Namibia
| | - Giovanni Franzo
- Department of Animal Medicine, Production and Health, University of Padova, Legnaro, Italy
| | - Lourens de Villiers
- School of Veterinary Medicine, Faculty of Health Sciences and Veterinary Medicine, University of Namibia, Windhoek, Namibia
| | - Leandra van Zyl
- School of Veterinary Medicine, Faculty of Health Sciences and Veterinary Medicine, University of Namibia, Windhoek, Namibia
| | - Mari de Villiers
- School of Veterinary Medicine, Faculty of Health Sciences and Veterinary Medicine, University of Namibia, Windhoek, Namibia
| | | | - Frank Busch
- Institute of International Animal Health/One Health, Friedrich-Loeffler-Institut, Federal Institute for Animal Health, Greifswald – Insel Riems, Germany
| | - Sascha Knauf
- Institute of International Animal Health/One Health, Friedrich-Loeffler-Institut, Federal Institute for Animal Health, Greifswald – Insel Riems, Germany
- One Health/International Animal Health, Faculty of Veterinary Medicine, Justus Liebig University, Giessen, Germany
| | - Klaas Dietze
- Institute of International Animal Health/One Health, Friedrich-Loeffler-Institut, Federal Institute for Animal Health, Greifswald – Insel Riems, Germany
| | - Martin Eiden
- Institute for Novel and Emerging Infectious Diseases, Friedrich-Loeffler-Institut, Greifswald-Insel Riems, Germany
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9
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Bienz M, Renaud C, Liu JR, Wong P, Pelletier P. Hepatitis E Virus in the United States and Canada: Is It Time to Consider Blood Donation Screening? Transfus Med Rev 2024; 38:150835. [PMID: 39059853 DOI: 10.1016/j.tmrv.2024.150835] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2024] [Revised: 04/14/2024] [Accepted: 04/17/2024] [Indexed: 07/28/2024]
Abstract
Hepatitis E virus (HEV) is the most common cause of acute viral hepatitis in the world and can lead to severe complications in immunocompromised individuals. HEV is primarily transmitted through eating pork, which has led to an increased in anti-HEV IgG seropositivity in the general population of Europe in particular. However, it can also be transmitted intravenously, such as through transfusions. The growing evidence of HEV contamination of blood products and documented cases of transmission have given rise to practice changes and blood product screening of HEV in many European countries. This review covers the abundant European literature and focuses on the most recent data pertaining to the prevalence of HEV RNA positivity and IgG seropositivity in the North American general population and in blood products from Canada and the United States. Currently, Health Canada and the Food and Drug Administration do not require testing of HEV in blood products. For this reason, awareness among blood product prescribers about the possibility of HEV transmission through blood products is crucial. However, we also demonstrate that the province of Quebec has a prevalence of anti-HEV and HEV RNA positivity similar to some European countries. In light of this, we believe that HEV RNA blood donation screening be reevaluated with the availability of more cost-effective assays.
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Affiliation(s)
- Marc Bienz
- Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada; Division of Hematology, Department of Medicine, McGill University, Montreal, Quebec, Canada.
| | - Christian Renaud
- Department of Microbiology, Infectious diseases, and Immunology, Université de Montréal, Montreal, Quebec, Canada; Medical Affairs and Innovation, Héma-Québec, Montreal, Quebec, Canada
| | - Jia Ru Liu
- Faculty of Medicine, Université de Montréal, Montreal, Quebec, Canada
| | - Philip Wong
- Division of Gastroenterology and Hepatology, Department of Medicine, McGill University Health Centre, Montreal, Quebec, Canada
| | - Patricia Pelletier
- Division of Hematology, Department of Medicine, McGill University, Montreal, Quebec, Canada
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Liu D, Liu B, He Z, Qiao C, Luo Q, Chen X, Wang X, Xiang H, Chen J, Zhang P, Huang Y, Wang G, Tan C, Cai R. Seroprevalence survey of Hepatitis E Virus in Domestic Pigs in Guangdong, China. Animals (Basel) 2024; 14:1861. [PMID: 38997973 PMCID: PMC11240697 DOI: 10.3390/ani14131861] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2024] [Revised: 06/20/2024] [Accepted: 06/20/2024] [Indexed: 07/14/2024] Open
Abstract
The Hepatitis E virus (HEV) causes acute and chronic Hepatitis E and is a global public health concern. HEV genotypes 3 (HEV-3) and 4 (HEV-4) are common to humans and animals, and domestic pigs and wild boars have been identified as the main reservoirs. However, limited information is available on the status of HEV infection in pigs, particularly in the Guangdong Province, China. This study aimed to investigate the seroprevalence of HEV in pig farms within the Guangdong Province. A total of 1568 serum samples were collected from 25 farms and tested for anti-HEV IgG antibodies. Enzyme-linked immunosorbent assay (ELISA) results revealed that 57.53% (902/1568) of serum samples from 24 farms (24/25, 96%) were positive for anti-HEV IgG antibodies. Year, season, region, and age were all linked risk factors for HEV in Guangdong, with season and region showing more significant impacts. The results showing a high seroprevalence of HEV confirmed its circulation among domestic pigs in the Guangdong Province, China. The presence of this antibody indicates that HEV infection was or is present on farms, posing a risk of zoonotic transmission of HEV from pigs to exposed workers and from pork or organs to consumption.
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Affiliation(s)
- Dingyu Liu
- Key Laboratory of Livestock Disease Prevention of Guangdong Province, Key Laboratory for Prevention and Control of Avian Influenza and Other Major Poultry Diseases, Ministry of Agriculture and Rural Affairs, Institute of Animal Health, Guangdong Academy of Agricultural Sciences, Guangzhou 510640, China; (D.L.)
- College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China
| | - Baoling Liu
- Key Laboratory of Livestock Disease Prevention of Guangdong Province, Key Laboratory for Prevention and Control of Avian Influenza and Other Major Poultry Diseases, Ministry of Agriculture and Rural Affairs, Institute of Animal Health, Guangdong Academy of Agricultural Sciences, Guangzhou 510640, China; (D.L.)
| | - Zhenwen He
- Key Laboratory of Livestock Disease Prevention of Guangdong Province, Key Laboratory for Prevention and Control of Avian Influenza and Other Major Poultry Diseases, Ministry of Agriculture and Rural Affairs, Institute of Animal Health, Guangdong Academy of Agricultural Sciences, Guangzhou 510640, China; (D.L.)
- College of Animal Science and Technology, Zhongkai University of Agriculture and Engineering, Guangzhou 510225, China
| | - Changhong Qiao
- Key Laboratory of Livestock Disease Prevention of Guangdong Province, Key Laboratory for Prevention and Control of Avian Influenza and Other Major Poultry Diseases, Ministry of Agriculture and Rural Affairs, Institute of Animal Health, Guangdong Academy of Agricultural Sciences, Guangzhou 510640, China; (D.L.)
| | - Qin Luo
- Key Laboratory of Livestock Disease Prevention of Guangdong Province, Key Laboratory for Prevention and Control of Avian Influenza and Other Major Poultry Diseases, Ministry of Agriculture and Rural Affairs, Institute of Animal Health, Guangdong Academy of Agricultural Sciences, Guangzhou 510640, China; (D.L.)
| | - Xiangyu Chen
- Key Laboratory of Livestock Disease Prevention of Guangdong Province, Key Laboratory for Prevention and Control of Avian Influenza and Other Major Poultry Diseases, Ministry of Agriculture and Rural Affairs, Institute of Animal Health, Guangdong Academy of Agricultural Sciences, Guangzhou 510640, China; (D.L.)
| | - Xiaohu Wang
- Key Laboratory of Livestock Disease Prevention of Guangdong Province, Key Laboratory for Prevention and Control of Avian Influenza and Other Major Poultry Diseases, Ministry of Agriculture and Rural Affairs, Institute of Animal Health, Guangdong Academy of Agricultural Sciences, Guangzhou 510640, China; (D.L.)
| | - Hua Xiang
- Key Laboratory of Livestock Disease Prevention of Guangdong Province, Key Laboratory for Prevention and Control of Avian Influenza and Other Major Poultry Diseases, Ministry of Agriculture and Rural Affairs, Institute of Animal Health, Guangdong Academy of Agricultural Sciences, Guangzhou 510640, China; (D.L.)
| | - Jing Chen
- Key Laboratory of Livestock Disease Prevention of Guangdong Province, Key Laboratory for Prevention and Control of Avian Influenza and Other Major Poultry Diseases, Ministry of Agriculture and Rural Affairs, Institute of Animal Health, Guangdong Academy of Agricultural Sciences, Guangzhou 510640, China; (D.L.)
| | - Pian Zhang
- Key Laboratory of Livestock Disease Prevention of Guangdong Province, Key Laboratory for Prevention and Control of Avian Influenza and Other Major Poultry Diseases, Ministry of Agriculture and Rural Affairs, Institute of Animal Health, Guangdong Academy of Agricultural Sciences, Guangzhou 510640, China; (D.L.)
| | - Yuan Huang
- Key Laboratory of Livestock Disease Prevention of Guangdong Province, Key Laboratory for Prevention and Control of Avian Influenza and Other Major Poultry Diseases, Ministry of Agriculture and Rural Affairs, Institute of Animal Health, Guangdong Academy of Agricultural Sciences, Guangzhou 510640, China; (D.L.)
| | - Gang Wang
- Key Laboratory of Livestock Disease Prevention of Guangdong Province, Key Laboratory for Prevention and Control of Avian Influenza and Other Major Poultry Diseases, Ministry of Agriculture and Rural Affairs, Institute of Animal Health, Guangdong Academy of Agricultural Sciences, Guangzhou 510640, China; (D.L.)
| | - Chen Tan
- College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China
| | - Rujian Cai
- Key Laboratory of Livestock Disease Prevention of Guangdong Province, Key Laboratory for Prevention and Control of Avian Influenza and Other Major Poultry Diseases, Ministry of Agriculture and Rural Affairs, Institute of Animal Health, Guangdong Academy of Agricultural Sciences, Guangzhou 510640, China; (D.L.)
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Santos-Silva S, Moraes DFDSD, López-López P, Paupério J, Queirós J, Rivero-Juarez A, Lux L, Ulrich RG, Gonçalves HMR, Van der Poel WHM, Nascimento MSJ, Mesquita JR. Detection of hepatitis E virus genotype 3 in an Algerian mouse (Mus spretus) in Portugal. Vet Res Commun 2024; 48:1803-1812. [PMID: 38243141 PMCID: PMC11147874 DOI: 10.1007/s11259-024-10293-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2023] [Accepted: 01/03/2024] [Indexed: 01/21/2024]
Abstract
Virus monitoring in small mammals is central to the design of epidemiological control strategies for rodent-borne zoonotic viruses. Synanthropic small mammals are versatile and may be potential carriers of several microbial agents. In the present work, a total of 330 fecal samples of small mammals were collected at two sites in the North of Portugal and screened for zoonotic hepatitis E virus (HEV, species Paslahepevirus balayani). Synanthropic small mammal samples (n = 40) were collected in a city park of Porto and belonged to the species Algerian mouse (Mus spretus) (n = 26) and to the greater white-toothed shrew (Crocidura russula) (n = 14). Furthermore, additional samples were collected in the Northeast region of Portugal and included Algerian mouse (n = 48), greater white-toothed shrew (n = 47), wood mouse (Apodemus sylvaticus) (n = 43), southwestern water vole (Arvicola sapidus) (n = 52), Cabrera's vole (Microtus cabrerae) (n = 49) and Lusitanian pine vole (Microtus lusitanicus) (n = 51). A nested RT-PCR targeting a part of open reading frame (ORF) 2 region of the HEV genome was used followed by sequencing and phylogenetic analysis. HEV RNA was detected in one fecal sample (0.3%; 95% confidence interval, CI: 0.01-1.68) from a synanthropic Algerian mouse that was genotyped as HEV-3, subgenotype 3e. This is the first study reporting the detection of HEV-3 in a synanthropic rodent, the Algerian mouse. The identified HEV isolate is probably the outcome of either a spill-over infection from domestic pigs or wild boars, or the result of passive viral transit through the intestinal tract. This finding reinforces the importance in the surveillance of novel potential hosts for HEV with a particular emphasis on synanthropic animals.
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Affiliation(s)
- Sérgio Santos-Silva
- School of Medicine and Biomedical Sciences (ICBAS), University of Porto, Porto, Portugal
| | | | - Pedro López-López
- Unit of Infectious Diseases, Clinical Virology and Zoonoses, Instituto Maimonides de Investigación Biomédica de Córdoba (IMIBIC), Hospital Universitario Reina Sofia, Universidad de Córdoba (UCO), Cordoba, Spain
- Center for Biomedical Research Network (CIBER) in Infectious Diseases, Health Institute Carlos III, Madrid, Spain
| | - Joana Paupério
- European Molecular Biology Laboratory, European Bioinformatics Institute, Welcome Genome Campus, Hinxton, CB10 1SD, UK
| | - João Queirós
- CIBIO-Centro de Investigação em Biodiversidade e Recursos Genéticos, InBIO Laboratório Associado, Universidade do Porto, Campus de Vairão, Vairão, 4485-661, Portugal
- BIOPOLIS Program in Genomics, Biodiversity and Land Planning, CIBIO, Campus de Vairão, Vairão, 4485-661, Portugal
- Departamento de Biologia, Faculdade de Ciências, Universidade do Porto, Rua Campo Alegre s/n, Porto, 4169-007, Portugal
- EBM, Estação Biológica de Mértola, Mértola, 7750-329, Portugal
| | - António Rivero-Juarez
- Unit of Infectious Diseases, Clinical Virology and Zoonoses, Instituto Maimonides de Investigación Biomédica de Córdoba (IMIBIC), Hospital Universitario Reina Sofia, Universidad de Córdoba (UCO), Cordoba, Spain
- Center for Biomedical Research Network (CIBER) in Infectious Diseases, Health Institute Carlos III, Madrid, Spain
| | - Laura Lux
- University of Greifswald, Domstraße 11, 17489, Greifswald, Germany
| | - Rainer G Ulrich
- Institute of Novel and Emerging Infectious Diseases, Friedrich-Loeffler-Institut (FLI), Federal Research Institute for Animal Health, Südufer 10, 17493, Greifswald-Insel Riems, Germany
| | - Helena M R Gonçalves
- REQUIMTE, Instituto Superior de Engenharia do Porto, Porto, Portugal
- Biosensor NTech - Nanotechnology Services, Avenida da Liberdade, 249, 1º Andar, Lda, Lisboa, 1250-143, Portugal
| | - Wim H M Van der Poel
- Quantitative Veterinary Epidemiology, Wageningen University, Wageningen, The Netherlands
- Department Virology & Molecular Biology, Wageningen Bioveterinary Research, Lelystad, The Netherlands
| | | | - João R Mesquita
- School of Medicine and Biomedical Sciences (ICBAS), University of Porto, Porto, Portugal.
- Epidemiology Research Unit (EPIUnit), Instituto de Saúde Pública da Universidade do Porto, Porto, Portugal.
- Laboratory for Integrative and Translational Research in Population Health (ITR), Porto, Portugal.
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12
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Panajotov J, Falkenhagen A, Gadicherla AK, Johne R. Molecularly generated rat hepatitis E virus strains from human and rat show efficient replication in a human hepatoma cell line. Virus Res 2024; 344:199364. [PMID: 38522562 PMCID: PMC10995862 DOI: 10.1016/j.virusres.2024.199364] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2024] [Revised: 03/18/2024] [Accepted: 03/18/2024] [Indexed: 03/26/2024]
Abstract
The hepatitis E virus (HEV) can cause acute and chronic hepatitis in humans. Whereas HEV genotypes 1-4 of species Paslahepevirus balayani are commonly found in humans, infections with ratHEV (species Rocahepevirus ratti) were previously considered to be restricted to rats. However, several cases of human ratHEV infections have been described recently. To investigate the zoonotic potential of this virus, a genomic clone was constructed here based on sequence data of ratHEV strain pt2, originally identified in a human patient with acute hepatitis from Hongkong. For comparison, genomic clones of ratHEV strain R63 from a rat and of HEV genotype 3 strain 47832mc from a human patient were used. After transfection of in vitro-transcribed RNA from the genomic clones into the human hepatoma cell line HuH-7-Lunet BLR, virus replication was shown for all strains by increasing genome copy numbers in cell culture supernatants. These cells developed persistent virus infections, and virus particles in the culture supernatant as well as viral antigen within the cells were demonstrated. All three generated virus strains successfully infected fresh HuH-7-Lunet BLR cells. In contrast, the human hepatoma cell lines HuH-7 and PLC/PRF/5 could only be infected with the genotype 3 strain and to a lesser extent with ratHEV strain R63. Infection of the rat-derived hepatoma cell lines clone 9, MH1C1 and H-4-II-E did not result in efficient virus replication for either strain. The results indicate that ratHEV strains from rats and humans can infect human hepatoma cells. The replication efficiency is strongly dependent on the cell line and virus strain. The investigated rat hepatoma cell lines could not be infected and other rat-derived cells should be tested in future to identify permissive cell lines from rats. The developed genomic clone can represent a useful tool for future research investigating pathogenicity and zoonotic potential of ratHEV.
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Affiliation(s)
| | | | - Ashish K Gadicherla
- German Federal Institute for Risk Assessment, 10589 Berlin, Germany; Center for Quantitative Cell Imaging, University of Wisconsin, Madison, USA
| | - Reimar Johne
- German Federal Institute for Risk Assessment, 10589 Berlin, Germany.
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13
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Marion O, Izopet J, Kamar N. Which Hepatitis E virus to worry about in our transplant patients. Transpl Infect Dis 2024; 26:e14285. [PMID: 38872417 DOI: 10.1111/tid.14285] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2024] [Revised: 04/02/2024] [Accepted: 04/04/2024] [Indexed: 06/15/2024]
Affiliation(s)
- Olivier Marion
- Department of Nephrology and Organ Transplantation, Toulouse Rangueil University Hospital, INSERM UMR 1291, Toulouse Institute for Infectious and Inflammatory Diseases (Infinity), University Paul Sabatier, Toulouse, France
| | - Jacques Izopet
- Laboratory of Virology, Institut Fédératif de Biologie, Toulouse Rangueil University Hospital, INSERM UMR 1291, Toulouse Institute for Infectious and Inflammatory Diseases (Infinity), University Paul Sabatier, Toulouse, France
| | - Nassim Kamar
- Department of Nephrology and Organ Transplantation, Toulouse Rangueil University Hospital, INSERM UMR 1291, Toulouse Institute for Infectious and Inflammatory Diseases (Infinity), University Paul Sabatier, Toulouse, France
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14
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Park K, Kim J, Noh J, Kim K, Yang E, Kim SG, Cho HK, Byun KS, Kim JH, Lee YS, Shim JO, Shin M, Kim WK, Song JW. First detection and characterization of hepatitis E virus (Rocahepevirus ratti) from urban Norway rats (Rattus norvegicus) in the Republic of Korea. J Med Virol 2024; 96:e29401. [PMID: 38235603 DOI: 10.1002/jmv.29401] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2023] [Revised: 12/21/2023] [Accepted: 01/02/2024] [Indexed: 01/19/2024]
Abstract
Hepatitis E virus (HEV), an emerging zoonotic pathogen, poses a significant public health concern worldwide. Recently, rat HEV (Rocahepevirus ratti genotype C1; HEV-C1) has been reported to cause zoonotic infections and hepatitis in humans. Human infections with HEV-C1 are considered to be underestimated worldwide due to limited knowledge of transmission routes, genome epidemiology, and the risk assessment of zoonosis associated with these viruses. A total of 186 wild Norway rats (Rattus norvegicus) were collected from the Republic of Korea (ROK) between 2011 and 2021. The prevalence of HEV-C1 RNA was 8 of 180 (4.4%) by reverse-transcription polymerase chain reaction. We first reported three nearly whole-genome sequences of HEV-C1 newly acquired from urban rats in the ROK. Phylogenetic analysis demonstrated that Korea-indigenous HEV-C1 formed an independent genetic group with those derived from R. norvegicus rats in other countries, indicating geographical and genetic diversity. Our findings provide critical insights into the molecular prevalence, genome epidemiology, and zoonotic potential of Rocahepevirus. This report raises awareness of the presence of Rocahepevirus-related hepatitis E among physicians in the ROK.
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Affiliation(s)
- Kyungmin Park
- Department of Microbiology, Korea University College of Medicine, Seoul, Republic of Korea
- BK21 Graduate Program, Department of Biomedical Sciences, Korea University College of Medicine, Seoul, Republic of Korea
| | - Jongwoo Kim
- Department of Microbiology, Korea University College of Medicine, Seoul, Republic of Korea
- BK21 Graduate Program, Department of Biomedical Sciences, Korea University College of Medicine, Seoul, Republic of Korea
| | - Juyoung Noh
- Department of Microbiology, Korea University College of Medicine, Seoul, Republic of Korea
- BK21 Graduate Program, Department of Biomedical Sciences, Korea University College of Medicine, Seoul, Republic of Korea
| | - Kijin Kim
- Centre for Infectious Disease Genomics and One Health, Faculty of Health Sciences, Simon Fraser University, Burnaby, British Columbia, Canada
- Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, British Columbia, Canada
| | - Eunyoung Yang
- Department of Microbiology, Korea University College of Medicine, Seoul, Republic of Korea
- BK21 Graduate Program, Department of Biomedical Sciences, Korea University College of Medicine, Seoul, Republic of Korea
| | - Seong-Gyu Kim
- Department of Microbiology, Korea University College of Medicine, Seoul, Republic of Korea
- BK21 Graduate Program, Department of Biomedical Sciences, Korea University College of Medicine, Seoul, Republic of Korea
| | - Hee-Kyung Cho
- Department of Microbiology, Korea University College of Medicine, Seoul, Republic of Korea
- BK21 Graduate Program, Department of Biomedical Sciences, Korea University College of Medicine, Seoul, Republic of Korea
| | - Kwan Soo Byun
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Korea University Medical Center, Seoul, Republic of Korea
| | - Ji Hoon Kim
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Korea University Medical Center, Seoul, Republic of Korea
| | - Young-Sun Lee
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Korea University Medical Center, Seoul, Republic of Korea
| | - Jung Ok Shim
- Department of Pediatrics, Korea University College of Medicine, Seoul, Republic of Korea
| | - Minsoo Shin
- Department of Pediatrics, Korea University Ansan Hospital, Ansan, Republic of Korea
| | - Won-Keun Kim
- Department of Microbiology, College of Medicine, Hallym University, Chuncheon, Republic of Korea
- Institute of Medical Research, College of Medicine, Hallym University, Chuncheon, Republic of Korea
| | - Jin-Won Song
- Department of Microbiology, Korea University College of Medicine, Seoul, Republic of Korea
- BK21 Graduate Program, Department of Biomedical Sciences, Korea University College of Medicine, Seoul, Republic of Korea
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15
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Chen Z, Li G, Situ J, Li Z, Guo S, Huang Y, Wu S, Tang Z, Wen G, Wang S, Fang M, Wang Y, Yu H, Sridhar S, Zheng Z, Xia N. Redeveloping antigen detection kits for the diagnosis of rat hepatitis E virus. J Clin Microbiol 2023; 61:e0071023. [PMID: 38038482 PMCID: PMC10729709 DOI: 10.1128/jcm.00710-23] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2023] [Accepted: 10/07/2023] [Indexed: 12/02/2023] Open
Abstract
The emergence of Rocahepevirus ratti [species HEV ratti (r HEV)] as a causative agent of hepatitis E in humans presents a new potential threat to global public health. The R. ratti genotype 1 (r-1 HEV) variant only shares 50%-60% genomic identity with Paslahepevirus balayani [species HEV balayani (b HEV)] variants, which are the main causes of hepatitis E infection in humans. Here, we report antigen diagnoses for r-1 HEV and b HEV using an enzymatic immunoassay (EIA) method. We detected recombinant virus-like particles protein (HEV 239) of r HEV and b HEV using a collection of hepatitis E virus (HEV)-specific monoclonal antibodies. Two optimal candidates, the capture antibody P#1-H4 and the detection antibodies C145 (P#1-H4*/C145#) and C158 (P#1-H4*/C158#), were selected to detect antigen in infected rat samples and r-1 HEV- or b HEV-infected human clinical samples. The two candidates showed similar diagnostic efficacy to the Wantai HEV antigen kit in b HEV-infected clinical samples. Genomic divergence resulted in low diagnostic efficacy of the Wantai HEV antigen kit (0%, 0 of 10) for detecting r-1 HEV infection. Compared with the P#1-H4*/C145# candidate (80%, 8 of 10), the P#1-H4*/C158# candidate had excellent diagnostic efficacy in r-1 HEV-infected clinical samples (100%, 10 of 10). The two candidates bind to a discrete antigenic site that is highly conserved across r HEV and b HEV. P#1-H4*/C145# and P#1-H4*/C158# are efficacious candidate antibody combinations for rat HEV antigen detection.
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Affiliation(s)
- Zihao Chen
- State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, Department of Laboratory Medicine, School of Public Health, Xiamen University, Xiamen, Fujian, China
- National Institute of Diagnostics and Vaccine Development in Infectious Diseases, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Innovation Platform for Industry-Education Integration in Vaccine Research, NMPA Key Laboratory for Research and Evaluation of Infectious Disease Diagnostic Technology, School of Public Health, School of Life Sciences, Xiamen University, Xiamen, Fujian, China
| | - Guanghui Li
- State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, Department of Laboratory Medicine, School of Public Health, Xiamen University, Xiamen, Fujian, China
- National Institute of Diagnostics and Vaccine Development in Infectious Diseases, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Innovation Platform for Industry-Education Integration in Vaccine Research, NMPA Key Laboratory for Research and Evaluation of Infectious Disease Diagnostic Technology, School of Public Health, School of Life Sciences, Xiamen University, Xiamen, Fujian, China
| | - Jianwen Situ
- Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, China
| | - Zhiyong Li
- The First Affiliated Hospital of Xiamen University, Xiamen University, Xiamen, Fujian, China
| | - Shaoqi Guo
- State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, Department of Laboratory Medicine, School of Public Health, Xiamen University, Xiamen, Fujian, China
- National Institute of Diagnostics and Vaccine Development in Infectious Diseases, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Innovation Platform for Industry-Education Integration in Vaccine Research, NMPA Key Laboratory for Research and Evaluation of Infectious Disease Diagnostic Technology, School of Public Health, School of Life Sciences, Xiamen University, Xiamen, Fujian, China
| | - Yang Huang
- State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, Department of Laboratory Medicine, School of Public Health, Xiamen University, Xiamen, Fujian, China
- National Institute of Diagnostics and Vaccine Development in Infectious Diseases, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Innovation Platform for Industry-Education Integration in Vaccine Research, NMPA Key Laboratory for Research and Evaluation of Infectious Disease Diagnostic Technology, School of Public Health, School of Life Sciences, Xiamen University, Xiamen, Fujian, China
| | - Shusheng Wu
- Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, China
| | - Zimin Tang
- State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, Department of Laboratory Medicine, School of Public Health, Xiamen University, Xiamen, Fujian, China
- National Institute of Diagnostics and Vaccine Development in Infectious Diseases, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Innovation Platform for Industry-Education Integration in Vaccine Research, NMPA Key Laboratory for Research and Evaluation of Infectious Disease Diagnostic Technology, School of Public Health, School of Life Sciences, Xiamen University, Xiamen, Fujian, China
| | - Guiping Wen
- United Diagnostic and Research Center for Clinical Genetics, Women and Children’s Hospital, School of Medicine & School of Public Health, Xiamen University, Xiamen, Fujian, China
| | - Siling Wang
- State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, Department of Laboratory Medicine, School of Public Health, Xiamen University, Xiamen, Fujian, China
- National Institute of Diagnostics and Vaccine Development in Infectious Diseases, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Innovation Platform for Industry-Education Integration in Vaccine Research, NMPA Key Laboratory for Research and Evaluation of Infectious Disease Diagnostic Technology, School of Public Health, School of Life Sciences, Xiamen University, Xiamen, Fujian, China
| | - Mujin Fang
- State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, Department of Laboratory Medicine, School of Public Health, Xiamen University, Xiamen, Fujian, China
- National Institute of Diagnostics and Vaccine Development in Infectious Diseases, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Innovation Platform for Industry-Education Integration in Vaccine Research, NMPA Key Laboratory for Research and Evaluation of Infectious Disease Diagnostic Technology, School of Public Health, School of Life Sciences, Xiamen University, Xiamen, Fujian, China
| | - Yingbin Wang
- State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, Department of Laboratory Medicine, School of Public Health, Xiamen University, Xiamen, Fujian, China
- National Institute of Diagnostics and Vaccine Development in Infectious Diseases, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Innovation Platform for Industry-Education Integration in Vaccine Research, NMPA Key Laboratory for Research and Evaluation of Infectious Disease Diagnostic Technology, School of Public Health, School of Life Sciences, Xiamen University, Xiamen, Fujian, China
| | - Hai Yu
- State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, Department of Laboratory Medicine, School of Public Health, Xiamen University, Xiamen, Fujian, China
- National Institute of Diagnostics and Vaccine Development in Infectious Diseases, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Innovation Platform for Industry-Education Integration in Vaccine Research, NMPA Key Laboratory for Research and Evaluation of Infectious Disease Diagnostic Technology, School of Public Health, School of Life Sciences, Xiamen University, Xiamen, Fujian, China
| | - Siddharth Sridhar
- Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, China
- State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Hong Kong, China
- Carol Yu Centre for Infection, The University of Hong Kong, Hong Kong, China
| | - Zizheng Zheng
- State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, Department of Laboratory Medicine, School of Public Health, Xiamen University, Xiamen, Fujian, China
- National Institute of Diagnostics and Vaccine Development in Infectious Diseases, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Innovation Platform for Industry-Education Integration in Vaccine Research, NMPA Key Laboratory for Research and Evaluation of Infectious Disease Diagnostic Technology, School of Public Health, School of Life Sciences, Xiamen University, Xiamen, Fujian, China
| | - Ningshao Xia
- State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, Department of Laboratory Medicine, School of Public Health, Xiamen University, Xiamen, Fujian, China
- National Institute of Diagnostics and Vaccine Development in Infectious Diseases, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Innovation Platform for Industry-Education Integration in Vaccine Research, NMPA Key Laboratory for Research and Evaluation of Infectious Disease Diagnostic Technology, School of Public Health, School of Life Sciences, Xiamen University, Xiamen, Fujian, China
- Research Unit of Frontier Technology of Structural Vaccinology, Chinese Academy of Medical Sciences, Xiamen, Fujian, China
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16
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Benavent S, Carlos S, Reina G. Rocahepevirus ratti as an Emerging Cause of Acute Hepatitis Worldwide. Microorganisms 2023; 11:2996. [PMID: 38138140 PMCID: PMC10745784 DOI: 10.3390/microorganisms11122996] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2023] [Revised: 12/10/2023] [Accepted: 12/13/2023] [Indexed: 12/24/2023] Open
Abstract
The hepatitis E virus (HEV) is a widespread human infection that causes mainly acute infection and can evolve to a chronic manifestation in immunocompromised individuals. In addition to the common strains of hepatitis E virus (HEV-A), known as Paslahepevirus balayani, pathogenic to humans, a genetically highly divergent rat origin hepevirus (RHEV) can cause hepatitis possessing a potential risk of cross-species infection and zoonotic transmission. Rocahepevirus ratti, formerly known as Orthohepevirus C, is a single-stranded RNA virus, recently reassigned to Rocahepevirus genus in the Hepeviridae family, including genotypes C1 and C2. RHEV primarily infects rats but has been identified as a rodent zoonotic virus capable of infecting humans through the consumption of contaminated food or water, causing both acute and chronic hepatitis cases in both animals and humans. This review compiles data concluding that 60% (295/489) of RHEV infections are found in Asia, being the continent with the highest zoonotic and transmission potential. Asia not only has the most animal cases but also 16 out of 21 human infections worldwide. Europe follows with 26% (128/489) of RHEV infections in animals, resulting in four human cases out of twenty-one globally. Phylogenetic analysis and genomic sequencing will be employed to gather global data, determine epidemiology, and assess geographical distribution. This information will enhance diagnostic accuracy, pathogenesis understanding, and help prevent cross-species transmission, particularly to humans.
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Affiliation(s)
- Sara Benavent
- Microbiology Department, Clínica Universidad de Navarra, 31008 Pamplona, Spain; (S.B.); (G.R.)
| | - Silvia Carlos
- Department of Preventive Medicine and Public Health, Universidad de Navarra, 31008 Pamplona, Spain
- IdiSNA, Navarra Institute for Health Research, 31008 Pamplona, Spain
| | - Gabriel Reina
- Microbiology Department, Clínica Universidad de Navarra, 31008 Pamplona, Spain; (S.B.); (G.R.)
- IdiSNA, Navarra Institute for Health Research, 31008 Pamplona, Spain
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Boukhrissa H, Mechakra S, Mahnane A, Lacheheb A. Viral hepatitis E, zoonotic transmission in Algeria. Virusdisease 2023; 34:389-394. [PMID: 37780902 PMCID: PMC10533760 DOI: 10.1007/s13337-023-00840-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2023] [Accepted: 06/05/2023] [Indexed: 10/03/2023] Open
Abstract
Viral hepatitis E, a major cause of acute viral hepatitis in adults, is a global public health problem. The zoonotic potential of the virus is currently accepted in developed countries. In developing countries, where transmission is mainly enteric, data on the animal reservoir are very limited. Our objective was to identify a possible risk of zoonotic transmission in our region (eastern Algeria). Four hundred and thirty four sera from blood donors were analysed by an-ti-HEV IgG antibodies detection using a commercial ELISA kit. Study participants were asked about demographics, contact with farm animals, pets, rats, and with live or shot game during a hunting activity. The anti-HEV IgG seroprevalence was 17.05%. Two risk factors were identified; rat contact with a seroprevalence rate at 51.2% (p < 1p.1000), OR = 6.736 [95% CI 3, 42-13.26] and game contact with a seroprevalence at 33% (p = 0.003), OR = 2.76 [95% CI 1.37-5.56]. In summary, zoonotic transmission is possible in our region. Rats and game should be investigated for a probable animal reservoir.
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Affiliation(s)
- Houda Boukhrissa
- Department of Infectious Diseases, Faculty of Medicine, University Ferhat Abbas Setif 1, Sétif, Algeria
| | - Salah Mechakra
- Department of Infectious Diseases, Faculty of Medicine, University Ferhat Abbas Setif 1, Sétif, Algeria
| | - Abbes Mahnane
- Department of Infectious Diseases, Faculty of Medicine, University Ferhat Abbas Setif 1, Sétif, Algeria
| | - Abdelmadjid Lacheheb
- Department of Infectious Diseases, Faculty of Medicine, University Ferhat Abbas Setif 1, Sétif, Algeria
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18
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Situ J, Hon-Yin Lo K, Cai JP, Li Z, Wu S, Hon-Kiu Shun E, Foo-Siong Chew N, Yiu-Hung Tsoi J, Sze-Man Chan G, Hei-Man Chan W, Chik-Yan Yip C, Sze KH, Chi-Chung Cheng V, Yuen KY, Sridhar S. An immunoassay system to investigate epidemiology of Rocahepevirus ratti (rat hepatitis E virus) infection in humans. JHEP Rep 2023; 5:100793. [PMID: 37575885 PMCID: PMC10415708 DOI: 10.1016/j.jhepr.2023.100793] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/25/2022] [Revised: 03/23/2023] [Accepted: 04/14/2023] [Indexed: 08/15/2023] Open
Abstract
Background & Aims Rat hepatitis E virus (Rocahepevirus ratti; HEV-C1) is an emerging cause of hepatitis E that is divergent from conventional human-infecting HEV variants (Paslahepevirus balayani; HEV-A). Validated serological assays for HEV-C1 are lacking. We aimed to develop a parallel enzymatic immunoassay (EIA) system that identifies individuals with HEV-C1 exposure. We also aimed to conduct the first HEV-C1 seroprevalence study in humans using this validated EIA system. Methods Expressed HEV-A (HEV-A4 p239) and HEV-C1 (HEV-C1 p241) peptides were characterised. Blood samples were simultaneously tested in HEV-A4 p239 and HEV-C1 p241 IgG EIAs. An optical density (OD) cut-off-based interpretation algorithm for identifying samples seropositive for HEV-A or HEV-C1 was validated using RT-PCR-positive infection sera. This algorithm was used to measure HEV-C1 seroprevalence in 599 solid organ transplant recipients and 599 age-matched immunocompetent individuals. Results Both peptides formed virus-like particles. When run in HEV-A4 p239 and HEV-C1 p241 EIAs, HEV-A and HEV-C1 RT-PCR-positive samples formed distinct clusters with minimal overlap in a two-dimensional plot of optical density values. The final EIA interpretation algorithm showed high agreement with RT-PCR results (Cohen's κ = 0.959) and was able to differentiate HEV-A and HEV-C1 infection sera with an accuracy of 94.2% (95% CI: 85.8-98.4%). HEV-C1 IgG seroprevalence was 7/599 (1.2%) among solid organ transplant recipients and 4/599 (0.7%) among immunocompetent individuals. Five of 11 (45.5%) of these patients had history of transient hepatitis of unknown cause. Conclusions HEV-C1 exposure was identified in 11/1198 (0.92%) individuals in Hong Kong indicating endemic exposure. This is the first estimate of HEV-C1 seroprevalence in humans. The parallel IgG EIA algorithm is a valuable tool for investigating epidemiology and risk factors for HEV-C1 infection. Impact and Implications Rat hepatitis E virus has recently been discovered to infect humans, but antibody tests for this infection are lacking, making it difficult to gauge how common this infection is. We developed an antibody test algorithm that can identify individuals with past rat hepatitis E virus exposure. We used this algorithm to estimate rat hepatitis E exposure rates in humans in Hong Kong and found that approximately 1% of all tested people had been exposed to this virus previously.
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Affiliation(s)
- Jianwen Situ
- Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, China
| | - Kelvin Hon-Yin Lo
- Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, China
| | - Jian-Piao Cai
- Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, China
| | - Zhiyu Li
- Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, China
| | - Shusheng Wu
- Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, China
| | - Estie Hon-Kiu Shun
- Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, China
| | - Nicholas Foo-Siong Chew
- Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, China
| | - James Yiu-Hung Tsoi
- Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, China
| | - Gabriel Sze-Man Chan
- Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, China
| | - Winson Hei-Man Chan
- Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, China
| | - Cyril Chik-Yan Yip
- Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, China
| | - Kong Hung Sze
- Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, China
| | - Vincent Chi-Chung Cheng
- Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, China
| | - Kwok-Yung Yuen
- Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, China
- State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Hong Kong, China
- Carol Yu Centre for Infection, The University of Hong Kong, Hong Kong, China
- The Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The University of Hong Kong, Hong Kong, China
- Centre for Virology, Vaccinology and Therapeutics, Hong Kong Science and Technology Park, Hong Kong Special Administrative Region, Hong Kong, China
| | - Siddharth Sridhar
- Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, China
- State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Hong Kong, China
- Carol Yu Centre for Infection, The University of Hong Kong, Hong Kong, China
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Nemes K, Persson S, Simonsson M. Hepatitis A Virus and Hepatitis E Virus as Food- and Waterborne Pathogens-Transmission Routes and Methods for Detection in Food. Viruses 2023; 15:1725. [PMID: 37632066 PMCID: PMC10457876 DOI: 10.3390/v15081725] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2023] [Revised: 08/07/2023] [Accepted: 08/09/2023] [Indexed: 08/27/2023] Open
Abstract
Foodborne viruses are an important threat to food safety and public health. Globally, there are approximately 5 million cases of acute viral hepatitis due to hepatitis A virus (HAV) and hepatitis E virus (HEV) every year. HAV is responsible for numerous food-related viral outbreaks worldwide, while HEV is an emerging pathogen with a global health burden. The reported HEV cases in Europe have increased tenfold in the last 20 years due to its zoonotic transmission through the consumption of infected meat or meat products. HEV is considered the most common cause of acute viral hepatitis worldwide currently. This review focuses on the latest findings on the foodborne transmission routes of HAV and HEV and the methods for their detection in different food matrices.
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Affiliation(s)
- Katalin Nemes
- European Union Reference Laboratory for Foodborne Viruses, Swedish Food Agency, Dag Hammarskjölds väg 56 A, 75237 Uppsala, Sweden; (S.P.); (M.S.)
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20
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Tsachev I, Gospodinova K, Pepovich R, Takova K, Kundurzhiev T, Zahmanova G, Kaneva K, Baymakova M. First Insight into the Seroepidemiology of Hepatitis E Virus (HEV) in Dogs, Cats, Horses, Cattle, Sheep, and Goats from Bulgaria. Viruses 2023; 15:1594. [PMID: 37515279 PMCID: PMC10385379 DOI: 10.3390/v15071594] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2023] [Revised: 07/17/2023] [Accepted: 07/19/2023] [Indexed: 07/30/2023] Open
Abstract
In recent years, hepatitis E virus (HEV) infection has been found to be widespread among different animal species worldwide. In Bulgaria, high HEV seropositivity was found among pigs (60.3%), wild boars (40.8%), and East Balkan swine (82.5%). The aim of the present study was to establish the seroprevalence of HEV among dogs, cats, horses, cattle, sheep, and goats in Bulgaria. In total, 720 serum samples from six animal species were randomly collected: dogs-90 samples; cats-90; horses-180; cattle-180; sheep-90; and goats-90. The serum samples were collected from seven districts of the country: Burgas, Kardzhali, Pazardzhik, Plovdiv, Sliven, Smolyan, and Stara Zagora. The animal serum samples were tested for HEV antibodies using the commercial Wantai HEV-Ab ELISA kit (Beijing, China). The overall HEV seroprevalence among different animal species from Bulgaria was as follows: dogs-21.1%; cats-17.7%; horses-8.3%; cattle-7.7%; sheep-32.2%; and goats-24.4%. We found the lowest overall HEV seropositivity in Plovdiv district (6.2%; 4/64; p = 0.203) and Smolyan district (8.8%; 4/45; p = 0.129), vs. the highest in Pazardzhik district (21.6%; 29/134; p = 0.024) and Burgas district (28.8%; 26/90; p = 0.062). To the best of our knowledge, this is the first serological evidence of HEV infection in dogs, cats, horses, cattle, sheep, and goats from Bulgaria. We found high HEV seropositivity in small ruminants (sheep and goats), moderate seropositivity in pets (dogs and cats), and a low level of seropositivity in large animals (horses and cattle). Previous Bulgarian studies and the results of this research show that HEV infection is widespread among animals in our country. In this regard, the Bulgarian health authorities must carry out increased surveillance and control of HEV infection among animals in Bulgaria.
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Affiliation(s)
- Ilia Tsachev
- Department of Microbiology, Infectious and Parasitic Diseases, Faculty of Veterinary Medicine, Trakia University, 6000 Stara Zagora, Bulgaria
| | - Krasimira Gospodinova
- Department of Microbiology, Infectious and Parasitic Diseases, Faculty of Veterinary Medicine, Trakia University, 6000 Stara Zagora, Bulgaria
| | - Roman Pepovich
- Department of Infectious Pathology, Hygiene, Technology and Control of Foods from Animal Origin, Faculty of Veterinary Medicine, University of Forestry, 1797 Sofia, Bulgaria
| | - Katerina Takova
- Department of Plant Physiology and Molecular Biology, University of Plovdiv, 4000 Plovdiv, Bulgaria
| | - Todor Kundurzhiev
- Department of Occupational Medicine, Faculty of Public Health, Medical University, 1527 Sofia, Bulgaria
| | - Gergana Zahmanova
- Department of Plant Physiology and Molecular Biology, University of Plovdiv, 4000 Plovdiv, Bulgaria
- Department of Technology Transfer and IP Management, Center of Plant Systems Biology and Biotechnology, 4000 Plovdiv, Bulgaria
| | - Kristin Kaneva
- Department of Microbiology, Infectious and Parasitic Diseases, Faculty of Veterinary Medicine, Trakia University, 6000 Stara Zagora, Bulgaria
| | - Magdalena Baymakova
- Department of Infectious Diseases, Military Medical Academy, 1606 Sofia, Bulgaria
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21
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Zahmanova G, Takova K, Tonova V, Koynarski T, Lukov LL, Minkov I, Pishmisheva M, Kotsev S, Tsachev I, Baymakova M, Andonov AP. The Re-Emergence of Hepatitis E Virus in Europe and Vaccine Development. Viruses 2023; 15:1558. [PMID: 37515244 PMCID: PMC10383931 DOI: 10.3390/v15071558] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2023] [Revised: 07/11/2023] [Accepted: 07/13/2023] [Indexed: 07/30/2023] Open
Abstract
Hepatitis E virus (HEV) is one of the leading causes of acute viral hepatitis. Transmission of HEV mainly occurs via the fecal-oral route (ingesting contaminated water or food) or by contact with infected animals and their raw meat products. Some animals, such as pigs, wild boars, sheep, goats, rabbits, camels, rats, etc., are natural reservoirs of HEV, which places people in close contact with them at increased risk of HEV disease. Although hepatitis E is a self-limiting infection, it could also lead to severe illness, particularly among pregnant women, or chronic infection in immunocompromised people. A growing number of studies point out that HEV can be classified as a re-emerging virus in developed countries. Preventative efforts are needed to reduce the incidence of acute and chronic hepatitis E in non-endemic and endemic countries. There is a recombinant HEV vaccine, but it is approved for use and commercially available only in China and Pakistan. However, further studies are needed to demonstrate the necessity of applying a preventive vaccine and to create conditions for reducing the spread of HEV. This review emphasizes the hepatitis E virus and its importance for public health in Europe, the methods of virus transmission and treatment, and summarizes the latest studies on HEV vaccine development.
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Affiliation(s)
- Gergana Zahmanova
- Department of Plant Physiology and Molecular Biology, University of Plovdiv, 4000 Plovdiv, Bulgaria
- Department of Technology Transfer and IP Management, Center of Plant Systems Biology and Biotechnology, 4000 Plovdiv, Bulgaria
| | - Katerina Takova
- Department of Plant Physiology and Molecular Biology, University of Plovdiv, 4000 Plovdiv, Bulgaria
| | - Valeria Tonova
- Department of Plant Physiology and Molecular Biology, University of Plovdiv, 4000 Plovdiv, Bulgaria
| | - Tsvetoslav Koynarski
- Department of Animal Genetics, Faculty of Veterinary Medicine, Trakia University, 6000 Stara Zagora, Bulgaria
| | - Laura L Lukov
- Faculty of Sciences, Brigham Young University-Hawaii, Laie, HI 96762, USA
| | - Ivan Minkov
- Department of Technology Transfer and IP Management, Center of Plant Systems Biology and Biotechnology, 4000 Plovdiv, Bulgaria
- Institute of Molecular Biology and Biotechnologies, 4108 Markovo, Bulgaria
| | - Maria Pishmisheva
- Department of Infectious Diseases, Pazardzhik Multiprofile Hospital for Active Treatment, 4400 Pazardzhik, Bulgaria
| | - Stanislav Kotsev
- Department of Infectious Diseases, Pazardzhik Multiprofile Hospital for Active Treatment, 4400 Pazardzhik, Bulgaria
| | - Ilia Tsachev
- Department of Microbiology, Infectious and Parasitic Diseases, Faculty of Veterinary Medicine, Trakia University, 6000 Stara Zagora, Bulgaria
| | - Magdalena Baymakova
- Department of Infectious Diseases, Military Medical Academy, 1606 Sofia, Bulgaria
| | - Anton P Andonov
- Department of Medical Microbiology and Infectious Diseases, Max Rady College of Medicine, University of Manitoba, Winnipeg, MB R3T 2N2, Canada
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22
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Abstract
PURPOSE OF REVIEW Infection with hepatitis E virus (HEV) is a global health concern, yet a clinically underdiagnosed cause of acute and chronic hepatitis. The WHO estimates that 20 million people are infected with HEV annually, yet the epidemiology, diagnosis and prevention remain elusive in many clinical settings. RECENT FINDINGS Orthohepevirus A (HEV-A) genotypes 1 and 2 cause acute, self-limited hepatitis through faecal-oral transmission. In 2022, the first-ever vaccine campaign was implemented as a response to an HEV outbreak in an endemic region. HEV-A genotypes 3 and 4 are zoonotic infections that primarily cause chronic HEV infection in immunosuppressed populations. Pregnant women and immunocompromised persons are at high risk for severe illness in some settings. Another recent advance in our knowledge of HEV is the zoonotic transmission of Orthohepevirus C (HEV-C) to humans, presumably from contact with rodents and/or their excrement. Previously, HEV infection in humans was presumed to be limited to HEV-A only. SUMMARY Clinical recognition and accurate diagnosis are essential to the management of HEV infection and understanding the global burden of the disease. Epidemiology affects clinical presentations. Targeted response strategies in HEV outbreaks are needed for the prevention of disease, and vaccine campaigns may prove to be an effective part of these strategies.
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Affiliation(s)
| | - Kenneth E Sherman
- Division of Digestive Diseases, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA
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23
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Prpić J, Kunić A, Keros T, Lojkić I, Brnić D, Jemeršić L. Absence of Hepatitis E Virus (HEV) Circulation in the Most Widespread Wild Croatian Canine Species, the Red Fox ( Vulpes vulpes) and Jackal ( Canis aureus moreoticus). Microorganisms 2023; 11:microorganisms11040834. [PMID: 37110256 PMCID: PMC10145003 DOI: 10.3390/microorganisms11040834] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2023] [Revised: 03/11/2023] [Accepted: 03/22/2023] [Indexed: 04/29/2023] Open
Abstract
Hepatitis E virus (HEV) can infect a wide range of domestic and wild animals, and the identification of new host species is reported successively worldwide. Nevertheless, its zoonotic potential and natural transmission, especially in wildlife remains unclear, primarily due to the discrete nature of HEV infections. Since the red fox (Vulpus vulpus) is the most widespread carnivore worldwide, and has been recognized as a potential HEV reservoir, its role as a potent host species is of increasing interest. Another wild canine species, the jackal （Canis aureus moreoticus）, is becoming more important within the same habitat as that of the red fox since its number and geographical distribution have been rapidly growing. Therefore, we have chosen these wild species to determine their potential role in the epidemiology and persistence of HEV in the wilderness. The main reason for this is the finding of HEV and a rather high HEV seroprevalence in wild boars sharing the same ecological niche as the wild canine species, as well as the risk of the spread of HEV through red foxes into the outskirts of cities, where possible indirect and even direct contact with people are not excluded. Therefore, our study aimed to investigate the possibility of natural HEV infection of free-living wild canines, by testing samples for the presence of HEV RNA and anti-HEV antibodies to gain better epidemiological knowledge of the disease. For this purpose, 692 red fox and 171 jackal muscle extracts and feces samples were tested. Neither HEV RNA nor anti-HEV antibodies were detected. Although HEV circulation was not detected in the tested samples, to our knowledge, these are the first results that include jackals as a growing and important omnivore wildlife species for the presence of HEV infection in Europe.
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Affiliation(s)
- Jelena Prpić
- Croatian Veterinary Institute, Savska cesta 143, 10000 Zagreb, Croatia
| | - Ana Kunić
- Croatian Veterinary Institute, Savska cesta 143, 10000 Zagreb, Croatia
| | - Tomislav Keros
- Croatian Veterinary Institute, Savska cesta 143, 10000 Zagreb, Croatia
| | - Ivana Lojkić
- Croatian Veterinary Institute, Savska cesta 143, 10000 Zagreb, Croatia
| | - Dragan Brnić
- Croatian Veterinary Institute, Savska cesta 143, 10000 Zagreb, Croatia
| | - Lorena Jemeršić
- Croatian Veterinary Institute, Savska cesta 143, 10000 Zagreb, Croatia
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24
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Higher Risk of HEV Transmission and Exposure among Blood Donors in Europe and Asia in Comparison to North America: A Meta-Analysis. Pathogens 2023; 12:pathogens12030425. [PMID: 36986347 PMCID: PMC10059948 DOI: 10.3390/pathogens12030425] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2023] [Revised: 03/01/2023] [Accepted: 03/05/2023] [Indexed: 03/10/2023] Open
Abstract
Background and aims: The increasing number of diagnosed hepatitis E virus (HEV) infections in Europe has led to the implementation of the testing of blood products in various countries. Many nations have not yet implemented such screening. To assess the need for HEV screening in blood products worldwide, we conducted a systematic review and meta-analysis assessing HEV RNA positivity and anti-HEV seroprevalence in blood donors. Methods: Studies reporting anti-HEV IgG/IgM or HEV RNA positivity rates among blood donors worldwide were identified via predefined search terms in PubMed and Scopus. Estimates were calculated by pooling study data with multivariable linear mixed-effects metaregression analysis. Results: A total of 157 (14%) of 1144 studies were included in the final analysis. The estimated HEV PCR positivity rate ranged from 0.01 to 0.14% worldwide, with strikingly higher rates in Asia (0.14%) and Europe (0.10%) in comparison to North America (0.01%). In line with this, anti-HEV IgG seroprevalence in North America (13%) was lower than that in Europe (19%). Conclusions: Our data demonstrate large regional differences regarding the risk of HEV exposure and blood-borne HEV transmission. Considering the cost–benefit ratio, this supports blood product screening in high endemic areas, such as Europe and Asia, in contrast to low endemic regions, such as the U.S.
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25
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Fernández Villalobos NV, Kessel B, Torres Páez JC, Strömpl J, Kerrinnes T, de la Hoz Restrepo FP, Strengert M, Krause G. Seroprevalence of Hepatitis E virus in children and adolescents living in urban Bogotá: An explorative cross-sectional study. Front Public Health 2023; 11:981172. [PMID: 36844812 PMCID: PMC9943700 DOI: 10.3389/fpubh.2023.981172] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2022] [Accepted: 01/06/2023] [Indexed: 02/09/2023] Open
Abstract
The majority of Hepatitis E Virus (HEV)-related studies are carried out in adults whereas information about HEV seroprevalence, clinical disease manifestation, molecular epidemiology, and transmission patterns in children is limited. To estimate HEV seroprevalence among scholar children living in an urban setting and to analyze risk factors for an infection, we invited children aged 5-18 years from Bogotá (Colombia) for a cross-sectional survey. We collected self-reported data on demographics, social, clinical, and exposure variables in a structured interview. Venous blood samples were analyzed with two commercially available ELISAs for HEV-specific IgG antibodies. Among the 263 participants, we found three HEV IgG-reactive samples (1.1%) using both assays. We additionally characterized the samples for HEV IgM using a commercially available IgM ELISA and for HEV RNA. Here, we found one IgM-reactive sample, which was also reactive for IgG. In contrast, none of the IgM- and IgG-reactive sera samples showed detectable RNA levels indicating HEV exposure had not been recently. All participants reported access to drinking water and sanitary systems in their households and frequent hand washing routines (76-88%). Eighty percent of children reported no direct contact with pigs, but occasional pork consumption was common (90%). In contrast to the majority of studies performed in Colombian adults, we found a low unadjusted HEV seroprevalence of 1.1% (95% CI: 0.3-3.6%) for both HEV IgG ELISAs in our study population. While the majority of participants reported pork consumption, we speculate in the absence of viral RNA for genotyping in the affected individuals, that existing access to drinking water and sanitary systems within our study group contribute to the low HEV seroprevalence.
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Affiliation(s)
| | - Barbora Kessel
- Department of Epidemiology, Helmholtz Centre for Infection Research (HZI), Braunschweig, Germany
| | - Johanna Carolina Torres Páez
- Department of Epidemiology, PhD Programme, Helmholtz Centre for Infection Research (HZI), Braunschweig-Hannover, Hannover, Germany
| | - Julia Strömpl
- Department of Epidemiology, Helmholtz Centre for Infection Research (HZI), Braunschweig, Germany
| | - Tobias Kerrinnes
- Department of RNA-Biology of Bacterial Infections, Helmholtz Institute for RNA-based Infection Research (HIRI), Würzburg, Germany
| | | | - Monika Strengert
- Department of Epidemiology, Helmholtz Centre for Infection Research (HZI), Braunschweig, Germany,Twincore, Centre for Experimental and Clinical Infection Research, A Joint Venture of the Hannover Medical School and Helmholtz Centre for Infection Research, Hannover, Germany,*Correspondence: Monika Strengert ✉
| | - Gérard Krause
- Department of Epidemiology, Helmholtz Centre for Infection Research (HZI), Braunschweig, Germany,Twincore, Centre for Experimental and Clinical Infection Research, A Joint Venture of the Hannover Medical School and Helmholtz Centre for Infection Research, Hannover, Germany,German Center for Infection Research (DZIF), partner site: Braunschweig-Hannover, Braunschweig, Germany
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26
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Caballero-Gómez J, García-Bocanegra I, Cano-Terriza D, Beato-Benítez A, Ulrich RG, Martínez J, Guerra R, Martínez-Valverde R, Martínez-Nevado E, Ángel Quevedo-Muñoz M, Sierra-Arqueros C, Planas J, de Castro-García N, Rivero A, Rivero-Juarez A. Monitoring of hepatitis E virus in zoo animals from Spain, 2007-2021. Transbound Emerg Dis 2022; 69:3992-4001. [PMID: 36083467 PMCID: PMC10087427 DOI: 10.1111/tbed.14702] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2022] [Revised: 08/24/2022] [Accepted: 09/04/2022] [Indexed: 02/07/2023]
Abstract
Hepatitis E virus (HEV, family Hepeviridae) is an important emerging and zoonotic pathogen. In recent decades, the number of human cases of zoonotic hepatitis E has increased considerably in industrialized countries and HEV has been detected in an expanding range of mammal species. Although domestic pigs and wild boar are considered the main reservoirs of zoonotic HEV genotypes, the role of other susceptible animals in the epidemiology of the virus is still poorly understood. A large-scale, long-term study was carried out (1) to assess HEV exposure in captive zoo animals in Spain and (2) to determine the dynamics of seropositivity in individuals that were sampled longitudinally during the study period. Between 2007 and 2021, serum samples from 425 zoo animals belonging to 109 animal species (including artiodactyls, carnivores, perissodactyls, proboscideans and rodents) were collected from 11 different zoological parks in Spain. Forty-six of these animals at seven of these zoos were also longitudinally sampled. Anti-HEV antibodies were detected in 36 (8.5%; 95% CI: 5.8-11.1) of 425 sampled zoo animals. Specific antibodies against HEV-3 and HEV-C1 antigens were confirmed in ELISA-positive animals using western blot assay. Two of 46 longitudinally surveyed animals seroconverted during the study period. Seropositivity was significantly higher in carnivores and perissodactyls than in artiodactyls, and also during the period 2012-2016 compared with 2007-2011. HEV RNA was not detected in any of the 262 animals that could be tested by RT-PCR. To the best of the author's knowledge, this is the first large-scale, long-term surveillance on HEV in different orders of zoo mammals. Our results indicate exposure to HEV-3 and HEV-C1 in zoo animals in Spain and confirm a widespread but not homogeneous spatiotemporal circulation of HEV in captive species in this country. Further studies are required to determine the role of zoo species, particularly carnivores and perissodactyls, in the epidemiology of HEV and to clarify the origins of infection in zoological parks.
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Affiliation(s)
- Javier Caballero-Gómez
- Departamento Sanidad Animal, Grupo de Investigación en Sanidad Animal y Zoonosis (GISAZ), UIC Zoonosis y Enfermedades Emergentes ENZOEM, Universidad de Córdoba, Campus de Rabanales, Edificio Sanidad Animal, Córdoba, España.,Grupo de Virología Clínica y Zoonosis, Unidad de Enfermedades Infecciosas, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Hospital Universitario Reina Sofía, Universidad de Córdoba, Córdoba, Spain.,CIBERINFEC, ISCIII - CIBER de Enfermedades Infecciosas, Instituto de Salud Carlos III, Spain
| | - Ignacio García-Bocanegra
- Departamento Sanidad Animal, Grupo de Investigación en Sanidad Animal y Zoonosis (GISAZ), UIC Zoonosis y Enfermedades Emergentes ENZOEM, Universidad de Córdoba, Campus de Rabanales, Edificio Sanidad Animal, Córdoba, España.,CIBERINFEC, ISCIII - CIBER de Enfermedades Infecciosas, Instituto de Salud Carlos III, Spain
| | - David Cano-Terriza
- Departamento Sanidad Animal, Grupo de Investigación en Sanidad Animal y Zoonosis (GISAZ), UIC Zoonosis y Enfermedades Emergentes ENZOEM, Universidad de Córdoba, Campus de Rabanales, Edificio Sanidad Animal, Córdoba, España.,CIBERINFEC, ISCIII - CIBER de Enfermedades Infecciosas, Instituto de Salud Carlos III, Spain
| | - Adrián Beato-Benítez
- Departamento Sanidad Animal, Grupo de Investigación en Sanidad Animal y Zoonosis (GISAZ), UIC Zoonosis y Enfermedades Emergentes ENZOEM, Universidad de Córdoba, Campus de Rabanales, Edificio Sanidad Animal, Córdoba, España
| | - Rainer G Ulrich
- Institute of Novel and Emerging Infectious Diseases, Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, Greifswald-Insel Riems, Germany.,German Centre for Infection Research (DZIF), partner site Hamburg-Lübeck-Borstel-Riems, Greifswald-Insel Riems, Germany
| | | | | | | | | | | | | | | | | | - Antonio Rivero
- Grupo de Virología Clínica y Zoonosis, Unidad de Enfermedades Infecciosas, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Hospital Universitario Reina Sofía, Universidad de Córdoba, Córdoba, Spain.,CIBERINFEC, ISCIII - CIBER de Enfermedades Infecciosas, Instituto de Salud Carlos III, Spain
| | - Antonio Rivero-Juarez
- Grupo de Virología Clínica y Zoonosis, Unidad de Enfermedades Infecciosas, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Hospital Universitario Reina Sofía, Universidad de Córdoba, Córdoba, Spain.,CIBERINFEC, ISCIII - CIBER de Enfermedades Infecciosas, Instituto de Salud Carlos III, Spain
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Jelicic P, Ferenc T, Mrzljak A, Jemersic L, Janev-Holcer N, Milosevic M, Bogdanic M, Barbic L, Kolaric B, Stevanovic V, Vujica M, Jurekovic Z, Pavicic Saric J, Vilibic M, Vilibic-Cavlek T. Insights into hepatitis E virus epidemiology in Croatia. World J Gastroenterol 2022; 28:5494-5505. [PMID: 36312833 PMCID: PMC9611701 DOI: 10.3748/wjg.v28.i37.5494] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/16/2022] [Revised: 08/15/2022] [Accepted: 09/16/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Hepatitis E virus (HEV) is an emerging virus of global health concern. The seroprevalence rates differ greatly according to geographic region and population group. AIM To analyze the seroprevalence of HEV in exposed (animal-related professions) and nonexposed populations, as well as solid organ and hematopoietic stem cell transplant patients. METHODS Forestry workers (n = 93), hunters (n = 74), and veterinarians (n = 151) represented the exposed population. The general population (n = 126) and pregnant women (n = 118) constituted the control group. Transplant patients included liver transplant recipients (LTRs) (n = 83), kidney transplant recipients (KTRs) (n = 43), and hematopoietic stem cell transplant recipients (HSCRs) (n = 39). HEV immunoglobulin G antibodies were detected using the enzyme-linked immunosorbent assay and confirmed by the immunoblot test. RESULTS The HEV seroprevalence significantly differed between groups: Veterinarians 15.2%, hunters 14.9%, forestry workers 6.5%, general population 7.1%, and pregnant women 1.7%. In transplant patients, the seropositivity was highest in LTRs (19.3%), while in KTRs and HSCRs, the seroprevalence was similar to the general population (6.9% and 5.1%, respectively). A significant increase in seropositivity with age was observed from 2.9% in individuals less than 30 years to 23.5% in those older than 60 years. Sociodemographic characteristics (sex, educational level, area of residence, and number of household members), eating habits (game meat, offal, and pork products consumption), and environmental and housing conditions (drinking water supply, type of water drainage/sewer, waste disposal, domestic animals) were not associated with HEV seropositivity. However, individuals who reported a pet ownership were more often seropositive compared to those who did not have pet animals (12.5% vs 7.0%). CONCLUSION The results of this study showed that individuals in professional contact with animals and LTRs are at higher risk for HEV infection. In addition, age is a significant risk factor for HEV seropositivity.
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Affiliation(s)
- Pavle Jelicic
- Department of Environmental Health, Croatian Institute of Public Health, Zagreb 10000, Croatia
| | - Thomas Ferenc
- Department of Radiology, Merkur University Hospital, Zagreb 10000, Croatia
| | - Anna Mrzljak
- Department of Gastroenterology and Hepatology, University Hospital Center Zagreb, Zagreb 10000, Croatia
- School of Medicine, University of Zagreb, Zagreb 10000, Croatia
| | - Lorena Jemersic
- Department of Virology, Croatian Veterinary Institute, Zagreb 10000, Croatia
| | - Natasa Janev-Holcer
- Department of Environmental Health, Croatian Institute of Public Health, Zagreb 10000, Croatia
- Department of Social Medicine and Epidemiology, Faculty of Medicine University of Rijeka, Rijeka 51000, Croatia
| | - Milan Milosevic
- Department of Occupational and Environmental Health, Andrija Stampar School of Public Health, Zagreb 10000, Croatia
| | - Maja Bogdanic
- Department of Virology, Croatian Institute of Public Health, Zagreb 10000, Croatia
| | - Ljubo Barbic
- Department of Microbiology and Infectious Diseases with Clinic, Faculty of Veterinary Medicine University of Zagreb, Zagreb 10000, Croatia
| | - Branko Kolaric
- Department of Gerontology and Social Medicine, Andrija Stampar Teaching Institute of Public Health, Zagreb 10000, Croatia
| | - Vladimir Stevanovic
- Department of Microbiology and Infectious Diseases with Clinic, Faculty of Veterinary Medicine University of Zagreb, Zagreb 10000, Croatia
| | - Mateja Vujica
- Institute of Emergency Medicine of Krapina-Zagorje County, Krapina 49000, Croatia
| | - Zeljka Jurekovic
- Department of Nephrology, Merkur University Hospital, Zagreb 10000, Croatia
| | | | - Maja Vilibic
- Department for Social Psychiatry, Psychotherapy and Psychodiagnostics, University Clinical Hospital Center “Sestre Milosrdnice”, Zagreb 10000, Croatia
| | - Tatjana Vilibic-Cavlek
- School of Medicine, University of Zagreb, Zagreb 10000, Croatia
- Department of Virology, Croatian Institute of Public Health, Zagreb 10000, Croatia
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Kinast V, Klöhn M, Nocke MK, Todt D, Steinmann E. Hepatitis E virus species barriers: seeking viral and host determinants. Curr Opin Virol 2022; 56:101274. [PMID: 36283248 DOI: 10.1016/j.coviro.2022.101274] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2022] [Revised: 09/19/2022] [Accepted: 09/21/2022] [Indexed: 11/03/2022]
Abstract
The intimate relationship between virus and host cell can result in highly adapted viruses that are restricted to a single host. However, some viruses have the ability to infect multiple host species. Remarkably, hepatitis E viruses (HEV) comprise genotypes that are either 'single-host' or 'multi-host' genotypes, a trait that raises fundamental questions: Why do different genotypes differ in their host range, despite a high degree of genomic similarity? What are the underlying molecular determinants that shape species barriers? Here, we review the current knowledge of viral and host determinants that may affect the evolutionary trajectories of HEV. We also provide a perspective on techniques and methods that address open questions of HEV host range and adaptation.
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Affiliation(s)
- Volker Kinast
- Department of Molecular and Medical Virology, Ruhr University Bochum, Bochum, Germany; Department of Medical Microbiology and Virology, Carl von Ossietzky University Oldenburg, Oldenburg, Germany
| | - Mara Klöhn
- Department of Molecular and Medical Virology, Ruhr University Bochum, Bochum, Germany
| | - Maximilian K Nocke
- Department of Molecular and Medical Virology, Ruhr University Bochum, Bochum, Germany
| | - Daniel Todt
- Department of Molecular and Medical Virology, Ruhr University Bochum, Bochum, Germany; European Virus Bioinformatics Center (EVBC), 07743 Jena, Germany.
| | - Eike Steinmann
- Department of Molecular and Medical Virology, Ruhr University Bochum, Bochum, Germany; German Centre for Infection Research (DZIF), External Partner Site, Bochum, Germany.
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Sridhar S, Wu S, Situ J, Shun EHK, Li Z, Zhang AJX, Hui K, Fong CHY, Poon VKM, Chew NFS, Yip CCY, Chan WM, Cai JP, Yuen KY. A small animal model of chronic hepatitis E infection using immunocompromised rats. JHEP Rep 2022; 4:100546. [PMID: 36052220 PMCID: PMC9424580 DOI: 10.1016/j.jhepr.2022.100546] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/08/2022] [Revised: 06/30/2022] [Accepted: 07/08/2022] [Indexed: 12/14/2022] Open
Abstract
Background & Aims HEV variants such as swine genotypes within Paslahepevirus species balayani (HEV-A) and rat HEV (Rocahepevirus ratti; HEV-C1) cause chronic hepatitis E in immunocompromised individuals. There are few reliable and accessible small animal models that accurately reflect chronic HEV infection. We aimed to develop an immunocompromised rat model of chronic hepatitis E infection. Methods In this animal model infection study, rats were immunosuppressed with a drug combination (prednisolone, tacrolimus, and mycophenolate mofetil) commonly taken by transplant recipients. Rats were challenged with human- and rat-derived HEV-C1 strains or a human-derived HEV-A strain. Viral load, liver function, liver histology, humoural, and cellular immune responses were monitored. Results A high-dose (HD) immunosuppressive regimen consistently prolonged human- and rat-derived HEV-C1 infection in rats (up to 12 weeks post infection) compared with transient infections in low-dose (LD) immunosuppressant-treated and immunocompetent (IC) rats. Mean HEV-C1 viral loads in stool, serum, and liver tissue were higher in HD regimen-treated rats than in LD or IC rats (p <0.05). Alanine aminotransferase elevation was observed in chronically infected rats, which was consistent with histological hepatitis and HEV-C1 antigen expression in liver tissue. None (0/6) of the HD regimen-treated, 5/6 LD regimen-treated, and 6/6 IC rats developed antibodies to HEV-C1 in species-specific immunoblots. Reversal of immunosuppression was associated with clearance of viraemia and restoration of HEV-C1-specific humoural and cellular immune responses in HD regimen-treated rats, mimicking patterns in treated patients with chronic hepatitis E. Viral load suppression was observed with i.p. ribavirin treatment. HD regimen-treated rats remained unsusceptible to HEV-A infection. Conclusions We developed a scalable immunosuppressed rat model of chronic hepatitis E that closely mimics this infection phenotype in transplant recipients. Lay summary Convenient small animal models are required for the study of chronic hepatitis E in humans. We developed an animal model of chronic hepatitis E by suppressing immune responses of rats with drugs commonly taken by humans as organ transplant rejection prophylaxis. This model closely mimicked features of chronic hepatitis E in humans.
Chronic HEV infection is challenging to model with small animals. Rats can be immunocompromised by transplant rejection drugs taken by patients. This model supports chronic rat HEV infection robustly and consistently. Immunosuppression in this model is scalable, reversible, and responsive to ribavirin.
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Key Words
- ALT, alanine aminotransferase
- HD, high dose
- HEV
- HEV, hepatitis E virus
- HEV-A, Paslahepevirus balayani
- HEV-C1
- HEV-C1, Rocahepevirus ratti genotype 1
- IC, immunocompetent
- IFN-γ, interferon-γ
- Immunosuppression
- LD, low dose
- MMF, mycophenolate mofetil
- Orthohepevirus C
- PBS, phosphate buffered saline
- Rat hepatitis E
- Ribavirin
- Rocahepevirus ratti
- VTM, virus transport medium
- dpi, days post infection
- rRT-PCR, real-time reverse-transcription PCR
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Affiliation(s)
- Siddharth Sridhar
- Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.,State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Hong Kong, China.,Carol Yu Centre for Infection, The University of Hong Kong, Hong Kong, China
| | - Shusheng Wu
- Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
| | - Jianwen Situ
- Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
| | - Estie Hon-Kiu Shun
- Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
| | - Zhiyu Li
- Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
| | - Anna Jin-Xia Zhang
- Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
| | - Kyle Hui
- Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
| | - Carol Ho-Yan Fong
- Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
| | - Vincent Kwok-Man Poon
- Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
| | - Nicholas Foo-Siong Chew
- Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
| | - Cyril Chik-Yan Yip
- Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
| | - Wan-Mui Chan
- Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
| | - Jian-Piao Cai
- Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
| | - Kwok-Yung Yuen
- Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.,State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Hong Kong, China.,Carol Yu Centre for Infection, The University of Hong Kong, Hong Kong, China.,The Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The University of Hong Kong, Hong Kong, China
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Current Knowledge of Hepatitis E Virus (HEV) Epidemiology in Ruminants. Pathogens 2022; 11:pathogens11101124. [PMID: 36297181 PMCID: PMC9609093 DOI: 10.3390/pathogens11101124] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2022] [Revised: 09/26/2022] [Accepted: 09/27/2022] [Indexed: 12/20/2022] Open
Abstract
Hepatitis E virus (HEV) infection represents an emerging public health concern worldwide. In industrialized countries, increasing numbers of autochthonous cases of human HEV infection are caused by zoonotic transmission of genotypes 3 and 4, mainly through the consumption of contaminated raw or undercooked meat of infected pigs and wild boars, which are considered the main reservoirs of HEV. However, in the last few years, accumulating evidence seems to indicate that several other animals, including different ruminant species, may harbor HEV. Understanding the impact of HEV infection in ruminants and identifying the risk factors affecting transmission among animals and to humans is critical in order to determine their role in the epidemiological cycle of HEV. In this review, we provide a summary of current knowledge on HEV ecology in ruminants. A growing body of evidence has revealed that these animal species may be potential important hosts of HEV, raising concerns about the possible implications for public health.
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Schemmerer M, Erl M, Wenzel JJ. HuH-7-Lunet BLR Cells Propagate Rat Hepatitis E Virus (HEV) in a Cell Culture System Optimized for HEV. Viruses 2022; 14:v14051116. [PMID: 35632857 PMCID: PMC9147593 DOI: 10.3390/v14051116] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2022] [Revised: 04/19/2022] [Accepted: 05/21/2022] [Indexed: 02/05/2023] Open
Abstract
The family Hepeviridae comprises the species Orthohepevirus A–D (HEV-A to -D). HEV-C genotype 1 (HEV-C1, rat HEV) is able to infect humans. This study investigated whether an optimized HEV-A cell culture system is able to propagate the cell culture-derived rat HEV, and if de novo isolation of the virus from rat liver is possible. We tested the liver carcinoma cell lines PLC/PRF/5, HuH-7, and HuH-7-Lunet BLR for their susceptibility to HEV-C1 strains. Cells were infected with the cell culture-derived HEV-C1 strain R63 and rat liver-derived strain R68. Cells were maintained in MEMM medium, which was refreshed every 3–4 days. The viral load of HEV-C1 was determined by RT-qPCR in the supernatant and expressed as genome copies per mL (c/mL). Rat HEV replication was most efficient in the newly introduced HuH-7-Lunet BLR cell line. Even if the rat HEV isolate had been pre-adapted to PLC/PRF/5 by multiple passages, replication in HuH-7-Lunet BLR was still at least equally effective. Only HuH-7-Lunet BLR cells were susceptible to the isolation of HEV-C1 from the liver homogenate. These results suggest HuH-7-Lunet BLR as the most permissive cell line for rat HEV. Our HEV-C1 cell culture system may be useful for basic research, the animal-free generation of large amounts of the virus as well as for the testing of antiviral compounds and drugs.
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32
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Behrendt P, Friesland M, Wißmann JE, Kinast V, Stahl Y, Praditya D, Hueffner L, Nörenberg PM, Bremer B, Maasoumy B, Steinmann J, Becker B, Paulmann D, Brill FHH, Steinmann J, Ulrich RG, Brüggemann Y, Wedemeyer H, Todt D, Steinmann E. Hepatitis E virus is highly resistant to alcohol-based disinfectants. J Hepatol 2022; 76:1062-1069. [PMID: 35085595 DOI: 10.1016/j.jhep.2022.01.006] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/14/2021] [Revised: 12/23/2021] [Accepted: 01/11/2022] [Indexed: 12/26/2022]
Abstract
BACKGROUND & AIMS Hepatitis E virus (HEV) is the most common cause of acute viral hepatitis worldwide and is mainly transmitted via the fecal-oral route or through consumption of contaminated food products. Due to the lack of efficient cell culture systems for the propagation of HEV, limited data regarding its sensitivity to chemical disinfectants are available. Consequently, preventive and evidence-based hygienic guidelines on HEV disinfection are lacking. METHODS We used a robust HEV genotype 3 cell culture model which enables quantification of viral infection of quasi-enveloped and naked HEV particles. For HEV genotype 1 infections, we used the primary isolate Sar55 in a fecal suspension. Standardized quantitative suspension tests using end point dilution and large-volume plating were performed for the determination of virucidal activity of alcohols (1-propanol, 2-propanol, ethanol), WHO disinfectant formulations and 5 different commercial hand disinfectants against HEV. Iodixanol gradients were conducted to elucidate the influence of ethanol on quasi-enveloped viral particles. RESULTS Naked and quasi-enveloped HEV was resistant to alcohols as well as alcohol-based formulations recommended by the WHO. Of the tested commercial hand disinfectants only 1 product displayed virucidal activity against HEV. This activity could be linked to phosphoric acid as an essential ingredient. Finally, we observed that ethanol and possibly non-active alcohol-based disinfectants disrupt the quasi-envelope structure of HEV particles, while leaving the highly transmissible and infectious naked virions intact. CONCLUSIONS Different alcohols and alcohol-based hand disinfectants were insufficient to eliminate HEV infectivity with the exception of 1 commercial ethanol-based product that included phosphoric acid. These findings have major implications for the development of measures to reduce viral transmission in clinical practice. LAY SUMMARY Hepatitis E virus (HEV) showed a high level of resistance to alcohols and alcohol-based hand disinfectants. The addition of phosphoric acid to alcohol was essential for virucidal activity against HEV. This information should be used to guide improved hygiene measures for the prevention of HEV transmission.
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Affiliation(s)
- Patrick Behrendt
- Institute for Experimental Virology, TWINCORE Centre for Experimental and Clinical Infection Research, A Joint Venture between the Medical School Hannover (MHH) and the Helmholtz Centre for Infection Research (HZI), Hannover, Germany; Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Germany; German Centre for Infection Research (DZIF), Hannover-Braunschweig, Germany.
| | - Martina Friesland
- Institute for Experimental Virology, TWINCORE Centre for Experimental and Clinical Infection Research, A Joint Venture between the Medical School Hannover (MHH) and the Helmholtz Centre for Infection Research (HZI), Hannover, Germany
| | - Jan-Erik Wißmann
- Department of Molecular and Medical Virology, Ruhr University Bochum, Bochum, Germany
| | - Volker Kinast
- Department of Molecular and Medical Virology, Ruhr University Bochum, Bochum, Germany
| | - Yannick Stahl
- Institute for Experimental Virology, TWINCORE Centre for Experimental and Clinical Infection Research, A Joint Venture between the Medical School Hannover (MHH) and the Helmholtz Centre for Infection Research (HZI), Hannover, Germany
| | - Dimas Praditya
- Department of Molecular and Medical Virology, Ruhr University Bochum, Bochum, Germany
| | - Lucas Hueffner
- Institute for Experimental Virology, TWINCORE Centre for Experimental and Clinical Infection Research, A Joint Venture between the Medical School Hannover (MHH) and the Helmholtz Centre for Infection Research (HZI), Hannover, Germany
| | - Pia Maria Nörenberg
- Institute for Experimental Virology, TWINCORE Centre for Experimental and Clinical Infection Research, A Joint Venture between the Medical School Hannover (MHH) and the Helmholtz Centre for Infection Research (HZI), Hannover, Germany
| | - Birgit Bremer
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Germany
| | - Benjamin Maasoumy
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Germany; German Centre for Infection Research (DZIF), Hannover-Braunschweig, Germany; Centre for Individualised Infection Medicine (CIIM), Hannover, Germany
| | - Jochen Steinmann
- Dr. Brill + Partner GmbH Institute for Hygiene and Microbiology, Bremen, Germany
| | - Britta Becker
- Dr. Brill + Partner GmbH Institute for Hygiene and Microbiology, Bremen, Germany
| | - Dajana Paulmann
- Dr. Brill + Partner GmbH Institute for Hygiene and Microbiology, Bremen, Germany
| | - Florian H H Brill
- Dr. Brill + Partner GmbH Institute for Hygiene and Microbiology, Bremen, Germany
| | - Joerg Steinmann
- Institute of Medical Microbiology, University Hospital Essen, University of Duisburg-Essen, Germany; Institute for Clinical Hygiene, Medical Microbiology and Infectiology, Clinic Nuernberg, Paracelsus Medical University, Nuremberg, Germany
| | - Rainer G Ulrich
- Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, Institute of Novel and Emerging Infectious Diseases, Greifswald-Insel Riems, Germany and German Centre for Infection Research (DZIF), Hamburg-Lübeck-Borstel-Insel Riems, Germany
| | - Yannick Brüggemann
- Department of Molecular and Medical Virology, Ruhr University Bochum, Bochum, Germany
| | - Heiner Wedemeyer
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Germany; German Centre for Infection Research (DZIF), Hannover-Braunschweig, Germany
| | - Daniel Todt
- Department of Molecular and Medical Virology, Ruhr University Bochum, Bochum, Germany; European Virus Bioinformatics Center (EVBC), Jena, Germany
| | - Eike Steinmann
- Department of Molecular and Medical Virology, Ruhr University Bochum, Bochum, Germany; German Centre for Infection Research (DZIF), External Partner Site, Bochum, Germany.
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No Evidence for Orthohepevirus C in Archived Human Samples in Germany, 2000–2020. Viruses 2022; 14:v14040742. [PMID: 35458471 PMCID: PMC9029421 DOI: 10.3390/v14040742] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2022] [Revised: 03/28/2022] [Accepted: 03/30/2022] [Indexed: 12/12/2022] Open
Abstract
Orthohepevirus C1, also known as rat hepatitis E virus (HEV), has been shown to sporadically cause disease in immunocompromised and immunocompetent adults. While routine serological assays vary in reactivity, rat HEV is not detected in routine HEV RT-PCR. Thus, such infections could be either missed or misclassified as conventional HEV (Orthohepevirus A) infections. We conducted a retrospective screening study among serum and plasma samples from patients suspected of having HEV infection, which were archived at the national consultant laboratory for HAV and HEV between 2000 and 2020. We randomly selected n = 200 samples, which were initially tested reactive (positive or borderline) for HEV-IgM and negative for HEV RNA and re-examined them using a highly sensitive Orthohepevirus C genotype 1-specific in-house RT-qPCR (LoD 95: 6.73 copies per reaction) and a nested RT-PCR broadly reactive for Orthohepevirus A and C. Conventional sanger sequencing was conducted for resulting PCR products. No atypical HEV strains were detected (0 of 200 [0.0%; 95% confidence interval: 0.0%–1.89%], indicating that Orthohepevirus C infections in the investigated population (persons with clinical suspicion of hepatitis E and positive HEV-IgM) are very rare.
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Experimental Cross-Species Transmission of Rat Hepatitis E Virus to Rhesus and Cynomolgus Monkeys. Viruses 2022; 14:v14020293. [PMID: 35215886 PMCID: PMC8880335 DOI: 10.3390/v14020293] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2021] [Revised: 01/13/2022] [Accepted: 01/26/2022] [Indexed: 11/24/2022] Open
Abstract
Rat hepatitis E virus (rat HEV) was first identified in wild rats and was classified as the species Orthohepevirus C in the genera Orthohepevirus, which is genetically different from the genotypes HEV-1 to HEV-8, which are classified as the species Orthohepevirus A. Although recent reports suggest that rat HEV transmits to humans and causes hepatitis, the infectivity of rat HEV to non-human primates such as cynomolgus and rhesus monkeys remains controversial. To investigate whether rat HEV infects non-human primates, we inoculated one cynomolgus monkey and five rhesus monkeys with a V-105 strain of rat HEV via an intravenous injection. Although no significant elevation of alanine aminotransferase (ALT) was observed, rat HEV RNA was detected in fecal specimens, and seroconversion was observed in all six monkeys. The partial nucleotide sequences of the rat HEV recovered from the rat HEV-infected monkeys were identical to those of the V-105 strain, indicating that the infection was caused by the rat HEV. The rat HEV recovered from the cynomolgus and rhesus monkeys successfully infected both nude and Sprague-Dawley rats. The entire rat HEV genome recovered from nude rats was identical to that of the V-105 strain, suggesting that the rat HEV replicates in monkeys and infectious viruses were released into the fecal specimens. These results demonstrated that cynomolgus and rhesus monkeys are susceptible to rat HEV, and they indicate the possibility of a zoonotic infection of rat HEV. Cynomolgus and rhesus monkeys might be useful as animal models for vaccine development.
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Johne R, Althof N, Nöckler K, Falkenhagen A. [Hepatitis E virus-a zoonotic virus: distribution, transmission pathways, and relevance for food safety]. Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz 2022; 65:202-208. [PMID: 34982174 PMCID: PMC8813789 DOI: 10.1007/s00103-021-03476-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2021] [Accepted: 12/07/2021] [Indexed: 11/27/2022]
Abstract
Das Hepatitis-E-Virus (HEV) ist ein Erreger einer akuten Hepatitis beim Menschen. Darüber hinaus treten zunehmend auch chronische Infektionen mit fataler Leberzirrhose bei immunsupprimierten Transplantationspatienten auf. Die Zahl der gemeldeten Hepatitis-E-Fälle in Deutschland hat in den vergangenen Jahren stark zugenommen. Hier kommt vor allem der Genotyp 3 vor, der zoonotisch von Tieren auf den Menschen übertragen werden kann. Haus- und Wildschweine, die ohne die Ausbildung klinischer Symptome infiziert werden, stellen das Hauptreservoir dar. In diesem Artikel werden die Verbreitung von HEV in Tieren in Deutschland, mögliche Übertragungswege des Virus und insbesondere die Bedeutung von Lebensmitteln bei der Übertragung anhand der aktuellen wissenschaftlichen Literatur dargestellt. HEV ist in Haus- und Wildschweinen in Deutschland stark verbreitet und wird hauptsächlich über direkten Kontakt oder den Verzehr von Lebensmitteln, die aus diesen Tieren hergestellt wurden, auf den Menschen übertragen. Beim HEV-RNA-Nachweis in spezifischen Lebensmitteln bleibt allerdings oft unklar, ob das enthaltene Virus noch infektiös ist oder durch die Herstellungsbedingungen inaktiviert wurde. Neuere Studien weisen auf eine hohe Stabilität des HEV unter verschiedenen physikochemischen Bedingungen hin, wohingegen eine Inaktivierung unter anderem durch Erhitzung erreicht wird. Generell wird deshalb ein ausreichendes Erhitzen von Schweinefleisch und -leber vor dem Verzehr empfohlen und für Risikogruppen zusätzlich der Verzicht auf den Verzehr kurzgereifter Rohwürste. Weitere Forschungen sind nötig, um relevante Risikolebensmittel zu identifizieren, alternative Übertragungswege zu untersuchen und effiziente Maßnahmen zu entwickeln, die eine zoonotische Virusübertragung zukünftig verringern oder vermeiden.
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Affiliation(s)
- Reimar Johne
- Bundesinstitut für Risikobewertung, Max-Dohrn-Str. 8-10, 10589, Berlin, Deutschland.
| | - Nadine Althof
- Bundesinstitut für Risikobewertung, Max-Dohrn-Str. 8-10, 10589, Berlin, Deutschland
| | - Karsten Nöckler
- Bundesinstitut für Risikobewertung, Max-Dohrn-Str. 8-10, 10589, Berlin, Deutschland
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Caballero-Gómez J, Rivero-Juarez A, Jurado-Tarifa E, Jiménez-Martín D, Jiménez-Ruiz E, Castro-Scholten S, Ulrich RG, López-López P, Rivero A, García-Bocanegra I. Serological and molecular survey of hepatitis E virus in cats and dogs in Spain. Transbound Emerg Dis 2021; 69:240-248. [PMID: 34951935 DOI: 10.1111/tbed.14437] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2021] [Revised: 12/04/2021] [Accepted: 12/21/2021] [Indexed: 11/29/2022]
Abstract
Hepatitis E virus (HEV) is an emerging zoonotic pathogen that is currently recognized as one of the major causes of acute human hepatitis worldwide. In Europe, the increasing number of hepatitis E cases is mainly associated with the consumption of animal food products or contact with infected animals. Dogs and cats have been suggested as a zoonotic source of HEV infection. The aim of this study was to assess Orthohepevirus circulation, including HEV-A, HEV-B and HEV-C species, in sympatric urban cats and dogs in southern Spain. Between 2017 and 2020, blood samples were collected from 144 stray cats and 152 dogs, both strays and pets. The presence of antibodies against HEV were tested using a double-antigen sandwich ELISA and seropositive samples were further analyzed by western blot. A RT-PCR was performed to detect RNA of Orthohepevirus species (HEV-A, HEV-B and HEV-C). A total of 19 (6.4%; 95%CI: 3.6-9.2) of the 296 animals tested showed anti-HEV antibodies by ELISA. Seropositivity was significantly higher in dogs (9.9%; 15/152; 95%CI: 5.1-14.6) than in cats (2.8%; 4/144; 95%CI: 0.1-5.5). Ten out of the 18 ELISA-positive animals that could be further analyzed by western blot, reacted against HEV-3 and/or HEV-C1 antigens, which suggest circulation of both genotypes in urban cats and dogs in the study area. However, HEV-A, HEV-B and HEV-C RNA was not detected in any of the tested sera. This is the first study to assess HEV circulation in both stray cats and dogs in Europe. Our results provide evidence of HEV exposure in sympatric urban cat and dog populations in southern Spain. Further studies are needed to determine the role of these species in the epidemiology of HEV. This article is protected by copyright. All rights reserved.
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Affiliation(s)
- Javier Caballero-Gómez
- Grupo de Investigación en Sanidad Animal y Zoonosis (GISAZ), Departamento de Sanidad Animal, Universidad de Córdoba, Córdoba, 14014, España.,Grupo de Virología Clínica y Zoonosis, Unidad de Enfermedades Infecciosas, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Hospital Universitario Reina Sofía, Universidad de Córdoba, Córdoba, 14004, España.,CIBERINFEC
| | - Antonio Rivero-Juarez
- Grupo de Virología Clínica y Zoonosis, Unidad de Enfermedades Infecciosas, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Hospital Universitario Reina Sofía, Universidad de Córdoba, Córdoba, 14004, España.,CIBERINFEC
| | - Estefanía Jurado-Tarifa
- Centro de Sanidad y Bienestar Animal (SBA), Empresa Municipal de Saneamiento de Córdoba (SADECO), Córdoba, 14005, España
| | - Débora Jiménez-Martín
- Grupo de Investigación en Sanidad Animal y Zoonosis (GISAZ), Departamento de Sanidad Animal, Universidad de Córdoba, Córdoba, 14014, España
| | - Elena Jiménez-Ruiz
- Centro de Sanidad y Bienestar Animal (SBA), Empresa Municipal de Saneamiento de Córdoba (SADECO), Córdoba, 14005, España
| | - Sabrina Castro-Scholten
- Grupo de Investigación en Sanidad Animal y Zoonosis (GISAZ), Departamento de Sanidad Animal, Universidad de Córdoba, Córdoba, 14014, España
| | - Rainer G Ulrich
- Institute of Novel and Emerging Infectious Diseases, Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, Greifswald-Insel Riems, 17493, Germany.,Deutsches Zentrum für Infektionsforschung (DZIF), partner site Hamburg-Lübeck-Borstel-Riems, Greifswald-Insel Riems, 17493, Germany
| | - Pedro López-López
- Grupo de Virología Clínica y Zoonosis, Unidad de Enfermedades Infecciosas, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Hospital Universitario Reina Sofía, Universidad de Córdoba, Córdoba, 14004, España.,CIBERINFEC
| | - Antonio Rivero
- Grupo de Virología Clínica y Zoonosis, Unidad de Enfermedades Infecciosas, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Hospital Universitario Reina Sofía, Universidad de Córdoba, Córdoba, 14004, España.,CIBERINFEC
| | - Ignacio García-Bocanegra
- Grupo de Investigación en Sanidad Animal y Zoonosis (GISAZ), Departamento de Sanidad Animal, Universidad de Córdoba, Córdoba, 14014, España.,CIBERINFEC
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Fanelli A, Tizzani P, Buonavoglia D. A systematic review and meta-analysis of hepatitis E virus (HEV) in wild boars. Res Vet Sci 2021; 142:54-69. [PMID: 34864434 DOI: 10.1016/j.rvsc.2021.11.015] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2021] [Revised: 05/02/2021] [Accepted: 11/26/2021] [Indexed: 12/19/2022]
Abstract
This systematic review and meta-analysis summarize the available information on Hepatitis E virus (HEV) -specific antibody seroprevalence and HEV RNA prevalence in wild boar, one of the most abundant game species worldwide. A literature search (CAB Abstracts, Web of Science, Embase and Scopus) was performed to find relevant peer-reviewed works published during the period 1990-2020. A random-effect model was carried out to calculate the pooled HEV-specific antibody seroprevalence and HEV RNA prevalence estimates with 95% confidence intervals, and I2 statistic was used to assess the heterogeneity of the data. Values by subgroups were compared according to the geographical area, age class (≤ 12 months old and > 12 months old), and sample type (bile, faeces, liver, meat/muscle, serum). Sixty-nine publications were selected, with the majority of the studies from Southern Europe (n = 27). The pooled HEV-specific antibody seroprevalence in wild boar was 28% (CI95% 23-34) and the HEV RNA prevalence 8% (CI95% 6-10). The analysis highlighted a significant heterogeneity among the estimates from the included studies (I2 = 98% and I2 = 95% for HEV-specific antibody seroprevalence and viral prevalence respectively). The moderator analysis indicated a statistically significant difference (p-value = 0.03) for the HEV RNA prevalence according to the sample type, with the highest value in bile (17%, CI95% 9-27), followed by liver (10%, CI95% 7-14), serum (7%, CI95% 4-10), faeces (5%, CI95% 2-9), and meat/muscle (3%, CI95% 0.04-10). Finally, the HEV RNA prevalence in Europe (8.7, CI95% 6.7-11) was significantly (p-value = 0.04) higher than in Asia (4, CI95% 0.6-8). The analysis highlights the important role of wild boar in the epidemiology of HEV.
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Affiliation(s)
- Angela Fanelli
- Department of Veterinary Medicine, University of Bari, Valenzano, Bari, Italy.
| | - Paolo Tizzani
- Department of Veterinary Sciences, University of Turin, Grugliasco, Turin, Italy
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Sridhar S, Yip CCY, Lo KHY, Wu S, Situ J, Chew NFS, Leung KH, Chan HSY, Wong SCY, Leung AWS, Tse CWS, Fung KSC, Tsang OTY, Hon KL, Cheng VCC, Ng KHL, Yuen KY. Hepatitis E virus species C infection in humans, Hong Kong. Clin Infect Dis 2021; 75:288-296. [PMID: 34718428 DOI: 10.1093/cid/ciab919] [Citation(s) in RCA: 57] [Impact Index Per Article: 14.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2021] [Indexed: 11/12/2022] Open
Abstract
BACKGROUND Hepatitis E virus (HEV) variants belonging to Orthohepevirus species A (HEV-A) are the primary cause of human hepatitis E. However, we previously reported that Orthohepevirus C (HEV-C1), a divergent HEV variant commonly found in rats, also causes hepatitis in humans. Here, we present a clinical-epidemiological investigation of human HEV-C1 infections detected in Hong Kong, with an emphasis on outcomes in immunocompromised individuals.. METHODS A surveillance system for detecting human HEV-C1 infections was established in Hong Kong. Epidemiological and clinical characteristics of HEV-C1 cases identified via this system between August 1, 2019 and December 31, 2020 were retrieved. Phylogenetic analysis of HEV-C1 strain sequences was performed. Infection outcomes of immunocompromised individuals with HEV-A and HEV-C1 infections were analyzed. RESULTS HEV-C1 accounted for 8/53 (15.1%) RT-PCR confirmed hepatitis E infections in Hong Kong during the study period, raising the total number of HEV-C1 infections detected in the city to 16. Two distinct HEV-C1 strain groups caused human infections. Patients were elderly and/or immunocompromised; half tested negative for HEV IgM. Cumulatively, HEV-C1 accounted for 9/21 (42.9%) cases of hepatitis E recorded in immunocompromised patients in Hong Kong. Immunocompromised HEV-C1 patients progressed to persistent hepatitis at similar rates (7/9; 77.8%) as HEV-A patients (10/12; 75%). HEV-C1 patients responded to oral ribavirin although response to first course was sometimes poor or delayed. CONCLUSIONS Dedicated RT-PCR-based surveillance detected human HEV-C1 cases that evade conventional hepatitis E diagnostic testing. Immunosuppressed HEV-C1-infected patients frequently progress to persistent HEV-C1 infection for which ribavirin is a suitable treatment option.
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Affiliation(s)
- Siddharth Sridhar
- Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.,State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong.,Carol Yu Centre for Infection, The University of Hong Kong
| | - Cyril Chik-Yan Yip
- Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
| | - Kelvin Hon-Yin Lo
- Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
| | - Shusheng Wu
- Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
| | - Jianwen Situ
- Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
| | - Nicholas Foo-Siong Chew
- Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
| | - Kit-Hang Leung
- Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
| | | | | | | | | | | | | | - Kam-Lun Hon
- The Hong Kong Children's Hospital, Hong Kong
| | - Vincent Chi-Chung Cheng
- Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
| | - Ken Ho-Leung Ng
- Public Health Laboratory Services Branch, Department of Health, Hong Kong
| | - Kwok-Yung Yuen
- Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.,State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong.,Carol Yu Centre for Infection, The University of Hong Kong.,The Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The University of Hong Kong
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Parraud D, Lhomme S, Péron JM, Da Silva I, Tavitian S, Kamar N, Izopet J, Abravanel F. Rat Hepatitis E Virus: Presence in Humans in South-Western France? Front Med (Lausanne) 2021; 8:726363. [PMID: 34540871 PMCID: PMC8448288 DOI: 10.3389/fmed.2021.726363] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2021] [Accepted: 08/10/2021] [Indexed: 12/21/2022] Open
Abstract
Background: Hepatitis E Virus (HEV) is one of the most common causes of hepatitis worldwide, and South-Western France is a high HEV seroprevalence area. While most cases of HEV infection are associated with the species Orthohepevirus-A, several studies have reported a few cases of HEV infections due to Orthohepevirus-C (HEV-C) that usually infects rats. Most of these human cases have occurred in immunocompromised patients. We have screened for the presence of HEV-C in our region. Methods and Results: We tested 224 sera, mostly from immunocompromised patients, for HEV-C RNA using an in-house real time RT-PCR. Liver function tests gave elevated results in 63% of patients: mean ALT was 159 IU/L (normal < 40 IU/L). Anti-HEV IgG (49%) and anti-HEV IgM (9.4%) were frequently present but none of the samples tested positive for HEV-C RNA. Conclusion: HEV-C does not circulate in the human population of South-Western France, despite the high seroprevalence of anti-HEV IgG.
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Affiliation(s)
- Delphine Parraud
- Virology Laboratory, National Reference Centre of Hepatitis E Viruses, Federal Institute of Biology, University Hospital, Toulouse, France
| | - Sébastien Lhomme
- Virology Laboratory, National Reference Centre of Hepatitis E Viruses, Federal Institute of Biology, University Hospital, Toulouse, France.,Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity) INSERM UMR1291-CNRS UMR5051-Université Toulouse III, Toulouse, France
| | - Jean Marie Péron
- Department of Gastroenterology, Rangueil University Hospital, Toulouse, France
| | - Isabelle Da Silva
- Virology Laboratory, National Reference Centre of Hepatitis E Viruses, Federal Institute of Biology, University Hospital, Toulouse, France
| | - Suzanne Tavitian
- Department of Hematology, Cancer University Institute of Toulouse, Toulouse, France
| | - Nassim Kamar
- Departments of Nephrology and Organ Transplantation, Rangueil University Hospital, INSERM U1043, IFR-BMT, University Paul Sabatier, Toulouse, France
| | - Jacques Izopet
- Virology Laboratory, National Reference Centre of Hepatitis E Viruses, Federal Institute of Biology, University Hospital, Toulouse, France.,Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity) INSERM UMR1291-CNRS UMR5051-Université Toulouse III, Toulouse, France
| | - Florence Abravanel
- Virology Laboratory, National Reference Centre of Hepatitis E Viruses, Federal Institute of Biology, University Hospital, Toulouse, France.,Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity) INSERM UMR1291-CNRS UMR5051-Université Toulouse III, Toulouse, France
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Mrzljak A, Balen I, Barbic L, Ilic M, Vilibic-Cavlek T. Hepatitis E virus in professionally exposed: A reason for concern? World J Hepatol 2021; 13:723-730. [PMID: 34367494 PMCID: PMC8326162 DOI: 10.4254/wjh.v13.i7.723] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/14/2021] [Revised: 03/31/2021] [Accepted: 06/25/2021] [Indexed: 02/06/2023] Open
Abstract
The zoonotic risk of hepatitis E virus (HEV) is well established. The HEV seroprevalence rates vary according to geographical region, assays used, and study cohorts. HEV infection is still underdiagnosed, implying the need to evaluate the disease's burden in the general population and specific risk groups, such as professionally exposed. Close contact with various animal reservoirs such as pigs, rabbits, sheep, dogs, wild boars, and deer has been associated with higher anti-HEV seroprevalence as a part of occupational exposure. While exact transmission routes remain to be determined, some general preventive measures such as proper hand hygiene, the usage of personal protective equipment, and the thermal processing of food before consumption should be followed. A "One-Health" multisectoral approach should be implemented to achieve optimal health and well-being outcomes, recognizing the interconnections between humans, animals, plants, and their shared environment, in which a vaccine against the zoonotic genotypes 3 and 4 and swine vaccination should be considered as a possible public health measure. This opinion review comprehensively addresses the HEV burden of professional exposure for butchers, slaughterhouse workers, veterinarians, farmers, hunters, and forestry workers delineates the current limits of protective work measures, and tackles future directions.
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Affiliation(s)
- Anna Mrzljak
- Department of Gastroenterology and Hepatology, University Hospital Centre Zagreb, Zagreb 10000, Croatia
- School of Medicine, University of Zagreb, Zagreb 10000, Croatia.
| | - Ivan Balen
- Department of Gastroenterology and Endocrinology, General Hospital “Dr. Josip Bencevic”, Slavonski Brod 35000, Croatia
| | - Ljubo Barbic
- Faculty of Veterinary Medicine, University of Zagreb, Zagreb 10000, Croatia
| | - Maja Ilic
- Department of Epidemiology, Croatian Institute of Public Health, School of Medicine, University of Zagreb, Zagreb 10000, Croatia
| | - Tatjana Vilibic-Cavlek
- School of Medicine, University of Zagreb, Zagreb 10000, Croatia
- Department of Virology, Croatian Institute of Public Health, School of Medicine, University of Zagreb, Zagreb 10000, Croatia
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Genetic Diversity and Epidemiological Significance of Wild Boar HEV-3 Strains Circulating in Poland. Viruses 2021; 13:v13061176. [PMID: 34205456 PMCID: PMC8235543 DOI: 10.3390/v13061176] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2021] [Revised: 05/24/2021] [Accepted: 06/15/2021] [Indexed: 01/06/2023] Open
Abstract
The wild boar is the most important reservoir of zoonotic HEV-3 strains among different wildlife species. The aim of the study was subtype identification of wild boar HEV-3 strains circulating in Poland. Wild boar liver was used in the study in the form of homogenates prepared from 57 samples positive for HEV in a real-time RT-PCR. These samples were collected from juvenile and adult wild boars hunted in the jurisdictions of different Regional Directorates of State Forests (RDSF) across Poland. Subtype identification of detected HEV strains was based on a phylogenetic analysis of the most conserved HEV ORF2 genome fragment. Out of 57 tested samples, consensus HEV ORF2 sequences of 348 bp were obtained for 45 strains. Nineteen strains were identified and belonged to the HEV gt 3a and 3i subtypes, whereas 26 were not assigned to any virus subtype. HEV gt 3i strains prevailed in the Polish wild boar population, 16 of such were identified, and they were significantly more often observed in the RDSF Katowice area (χ2 = 28.6, p = 0.027 (<0.05)) compared to other regions of the country. Circulation of 3a strains was limited only to the RDSF Gdańsk territory (χ2 = 48, p = 0.000 (<0.05)). The virus strains detected in the Polish population of wild boars representing previously identified HEV subtypes in wild boars, pigs, or humans in Europe are of epidemiological importance for public health.
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Production of capsid proteins of rat hepatitis E virus in Escherichia coli and characterization of self-assembled virus-like particles. Virus Res 2021; 302:198483. [PMID: 34146611 DOI: 10.1016/j.virusres.2021.198483] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2021] [Revised: 06/09/2021] [Accepted: 06/10/2021] [Indexed: 12/19/2022]
Abstract
Rat hepatitis E virus (HEV) has been isolated from wild rats worldwide and the potential of zoonotic transmission has been documented. Escherichia coli (E. coli) is utilized as an effective system for producing HEV-like particles. However, the production of rat HEV ORF2 proteins in E. coli forming virus-like particles (VLPs) has not yet been reported. In this study, nine rat HEV ORF2 proteins of the ratELOMB-131L strain with truncated N- and C-termini (amino acids 339-594, 349-594, 351-594, 354-594, 357-594, 357-599, 357-604, 357-609, and 357-614 of ORF2 protein) were expressed in E. coli and the 357-614 protein self-assembled most efficiently. A bioanalyzer showed that the purified 357-614 protein has a molecular weight of 33.5 kDa and a purity of 93.2%. Electron microscopy revealed that the purified 33.5 kDa protein formed VLPs with a diameter of 21-52 (average 32) nm, and immunoelectron microscopy using an anti-rat HEV ORF2 monoclonal antibody (TA7014) indicated that the observed VLPs were derived from rat HEV ORF2. The VLPs attached to and entered the PLC/PRF/5 cells and blocked the neutralization of rat HEV by TA7014, suggesting that the VLPs possess the antigenic structure of infectious rat HEV particles. In addition, rat HEV VLPs showed high immunogenicity in mice. The present results would be useful for future studies on the development of VLP-based vaccines for HEV prevention in a rat model and for the prevention of rat HEV infection in humans.
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A broadly cross-reactive monoclonal antibody against hepatitis E virus capsid antigen. Appl Microbiol Biotechnol 2021; 105:4957-4973. [PMID: 34129082 PMCID: PMC8236046 DOI: 10.1007/s00253-021-11342-7] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2020] [Revised: 04/28/2021] [Accepted: 05/09/2021] [Indexed: 12/27/2022]
Abstract
Abstract To generate a hepatitis E virus (HEV) genotype 3 (HEV-3)–specific monoclonal antibody (mAb), the Escherichia coli–expressed carboxy-terminal part of its capsid protein was used to immunise BALB/c mice. The immunisation resulted in the induction of HEV-specific antibodies of high titre. The mAb G117-AA4 of IgG1 isotype was obtained showing a strong reactivity with the homologous E. coli, but also yeast-expressed capsid protein of HEV-3. The mAb strongly cross-reacted with ratHEV capsid protein derivatives produced in both expression systems and weaker with an E. coli–expressed batHEV capsid protein fragment. In addition, the mAb reacted with capsid protein derivatives of genotypes HEV-2 and HEV-4 and common vole hepatitis E virus (cvHEV), produced by the cell-free synthesis in Chinese hamster ovary (CHO) and Spodoptera frugiperda (Sf21) cell lysates. Western blot and line blot reactivity of the mAb with capsid protein derivatives of HEV-1 to HEV-4, cvHEV, ratHEV and batHEV suggested a linear epitope. Use of truncated derivatives of ratHEV capsid protein in ELISA, Western blot, and a Pepscan analysis allowed to map the epitope within a partially surface-exposed region with the amino acid sequence LYTSV. The mAb was also shown to bind to human patient–derived HEV-3 from infected cell culture and to hare HEV-3 and camel HEV-7 capsid proteins from transfected cells by immunofluorescence assay. The novel mAb may serve as a useful tool for further investigations on the pathogenesis of HEV infections and might be used for diagnostic purposes. Key points • The antibody showed cross-reactivity with capsid proteins of different hepeviruses. • The linear epitope of the antibody was mapped in a partially surface-exposed region. • The antibody detected native HEV-3 antigen in infected mammalian cells. Supplementary Information The online version contains supplementary material available at 10.1007/s00253-021-11342-7.
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Multimodal investigation of rat hepatitis E virus antigenicity: Implications for infection, diagnostics, and vaccine efficacy. J Hepatol 2021; 74:1315-1324. [PMID: 33845058 DOI: 10.1016/j.jhep.2020.12.028] [Citation(s) in RCA: 42] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/05/2020] [Revised: 11/30/2020] [Accepted: 12/17/2020] [Indexed: 01/20/2023]
Abstract
BACKGROUND & AIMS Rat hepatitis E virus (Orthohepevirus species C; HEV-C1) is an emerging cause of viral hepatitis in humans. HEV-C1 is divergent from other HEV variants infecting humans that belong to Orthohepevirus species A (HEV-A). This study assessed HEV-C1 antigenic divergence from HEV-A and investigated the impact of this divergence on infection susceptibility, serological test sensitivity, and vaccine efficacy. METHODS Immunodominant E2s peptide sequences of HEV-A and HEV-C1 were aligned. Interactions of HEV-C1 E2s and anti-HEV-A monoclonal antibodies (mAbs) were modeled. Recombinant peptides incorporating E2s of HEV-A (HEV-A4 p239) and HEV-C1 (HEV-C1 p241) were expressed. HEV-A and HEV-C1 patient sera were tested using antibody enzymatic immunoassays (EIA), antigen EIAs, and HEV-A4 p239/HEV-C1 p241 immunoblots. Rats immunized with HEV-A1 p239 vaccine (Hecolin), HEV-A4 p239 or HEV-C1 p241 peptides were challenged with a HEV-C1 strain. RESULTS E2s sequence identity between HEV-A and HEV-C1 was only 48%. There was low conservation at E2s residues (23/53; 43.4%) involved in mAb binding. Anti-HEV-A mAbs bound HEV-C1 poorly in homology modeling and antigen EIAs. Divergence resulted in low sensitivity of commercial antigen (0%) and antibody EIAs (10-70%) for HEV-C1 diagnosis. Species-specific HEV-A4 p239/HEV-C1 p241 immunoblots accurately differentiated HEV-A and HEV-C1 serological profiles in immunized rats (18/18; 100%) and infected-patient sera (32/36; 88.9%). Immunization with Hecolin and HEV-A4 p239 was partially protective while HEV-C1 p241 was fully protective against HEV-C1 infection in rats. CONCLUSIONS Antigenic divergence significantly decreases sensitivity of hepatitis E serodiagnostic assays for HEV-C1 infection. Species-specific immunoblots are useful for diagnosing HEV-C1 and for differentiating the serological profiles of HEV-A and HEV-C1. Prior HEV-A exposure is not protective against HEV-C1. HEV-C1 p241 is an immunogenic vaccine candidate against HEV-C1. LAY SUMMARY Rat hepatitis E virus (HEV-C1) is a new cause of hepatitis in humans. Using a combination of methods, we showed that HEV-C1 is highly divergent from the usual cause of human hepatitis (HEV-A). This divergence reduces the capacity of existing tests to diagnose HEV-C1 and also indicates that prior exposure to HEV-A (via infection or vaccination) is not protective against HEV-C1.
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Dichtl K, Zimmermann J, Koeppel MB, Böhm S, Osterman A. Evaluation of a Novel CLIA Monotest Assay for the Detection of Anti-Hepatitis E Virus-IgG and IgM: A Retrospective Comparison with a Line Blot and an ELISA. Pathogens 2021; 10:pathogens10060689. [PMID: 34206114 PMCID: PMC8228023 DOI: 10.3390/pathogens10060689] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2021] [Revised: 05/25/2021] [Accepted: 05/28/2021] [Indexed: 12/27/2022] Open
Abstract
Despite the increasing relevance of Hepatitis E, an emerging disease endemic in developing and with increasing numbers of sporadic cases in industrialized countries, commercial tests are mainly based on batch oriented serological assays. In this retrospective study, we compared a line immunoassay (LIA; recomLine HEV, Mikrogen) and an ELISA (EIA; Anti-Hepatitis E Virus ELISA, Euroimmun) with a novel chemoluminescence immunoassay in a monotest format (CLIA; Hepatitis E VirClia, Vircell). Twenty sera of PCR proven cases of hepatitis E and 68 blood samples serologically pre-characterized were included. Applying the WHO reference standard, the CLIA demonstrated the highest analytical sensitivity for IgG and IgM. The combinations of CLIA/EIA (IgG and IgM) and CLIA/LIA (IgG) measurements showed substantial correlation. Compared to overall antibody detection (seropositivity in ≥2 assays), CLIA correlation was excellent, outperforming LIA (IgM) and EIA (IgG and IgM). Minor IgM cross reactivity in samples of patients with acute EBV infection was observed in all three assays. The CLIA showed good performance in diagnostic samples compared to established LIA and EIA assays. Due to its ready-to-use monotest format, the CLIA allows simple, time- and cost-effective handling of single samples. These qualities make the assay suitable for diagnostics, especially in the emergency setting and for low-throughput laboratories.
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Affiliation(s)
- Karl Dichtl
- Chair of Medical Microbiology and Hospital Epidemiology, Faculty of Medicine, Max von Pettenkofer-Institute, LMU Munich, D-80336 München, Germany; (K.D.); (J.Z.)
| | - Julia Zimmermann
- Chair of Medical Microbiology and Hospital Epidemiology, Faculty of Medicine, Max von Pettenkofer-Institute, LMU Munich, D-80336 München, Germany; (K.D.); (J.Z.)
- Chair of Virology, National Reference Center for Retroviruses, Faculty of Medicine, Max von Pettenkofer Institut, LMU München, D-80336 München, Germany;
- German Center for Infection Research (DZIF), Partner Site Munich, D-80539 Munich, Germany
| | | | - Stephan Böhm
- Chair of Virology, National Reference Center for Retroviruses, Faculty of Medicine, Max von Pettenkofer Institut, LMU München, D-80336 München, Germany;
- German Center for Infection Research (DZIF), Partner Site Munich, D-80539 Munich, Germany
| | - Andreas Osterman
- Chair of Virology, National Reference Center for Retroviruses, Faculty of Medicine, Max von Pettenkofer Institut, LMU München, D-80336 München, Germany;
- German Center for Infection Research (DZIF), Partner Site Munich, D-80539 Munich, Germany
- Correspondence:
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Alvarado-Esquivel C, Gutierrez-Martinez VD, Ramirez-Valles EG, Sifuentes-Alvarez A. Hepatitis E Virus Infection and Butchers: A Case-Control Seroprevalence Study. Gastroenterology Res 2021; 14:96-103. [PMID: 34007351 PMCID: PMC8110237 DOI: 10.14740/gr1198] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/17/2019] [Accepted: 07/11/2019] [Indexed: 12/14/2022] Open
Abstract
Background Very few case-control studies to assess the risk of hepatitis E virus (HEV) infection in meat workers have been published. Therefore, we sought to determine: 1) the association of HEV IgG seropositivity and the occupation of butcher; and 2) the sociodemographic, work, clinical and behavioral characteristics of butchers associated with HEV exposure. Methods We performed a case-control seroprevalence study of 101 butchers (mean age: 38.50 ± 12.52 years) and 101 age-, gender- and residence-matched control subjects of the general population. Anti-HEV IgG antibodies were determined using a commercially available enzyme-linked immunoassay. Bivariate and regression analyses were used to assess the association between HEV seropositivity and characteristics of butchers. Results Anti-HEV IgG antibodies were found in 18 (17.8%) of the 101 butchers and in 14 (13.9%) of the 101 control subjects (odds ratio (OR): 1.34; 95% confidence interval (CI): 0.63 - 2.88; P = 0.44). Stratification by sex, age and area of residence (rural or urban) in cases and controls showed similar seroprevalences of HEV infection among groups. Bivariate analysis showed that HEV seroprevalence was associated with low education (up to 6 years), work place, seniority, eating while working, a history of raising farm animals and national trips. However, further analysis by logistic regression showed that only the variable of national trips was associated with HEV exposure (OR: 5.38; 95% CI: 1.02 - 28.16; P = 0.04). Concerning clinical characteristics of butchers, no association between HEV exposure and health status, history of surgery or blood transfusion was found. Conclusions Results from this first age-, gender- and residence-matched serosurvey of HEV infection in butchers in Mexico suggest that this population group does not have a higher risk for HEV infection than people from the general population. However, further studies to confirm the lack of association between HEV infection and the occupation of butcher are needed.
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Affiliation(s)
- Cosme Alvarado-Esquivel
- Biomedical Research Laboratory, Faculty of Medicine and Nutrition, Juarez University of Durango State, Avenida Universidad S/N, 34000 Durango, Dgo, Mexico
| | | | - Eda Guadalupe Ramirez-Valles
- Faculty of Chemical Sciences, Juarez University of Durango State, Avenida Veterinarias S/N, 34120 Durango, Dgo, Mexico
| | - Antonio Sifuentes-Alvarez
- Biomedical Research Laboratory, Faculty of Medicine and Nutrition, Juarez University of Durango State, Avenida Universidad S/N, 34000 Durango, Dgo, Mexico
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Sridhar S, Yip CCY, Wu S, Chew NFS, Leung KH, Chan JFW, Zhao PS, Chan WM, Poon RWS, Tsoi HW, Cai JP, Chan HSY, Leung AWS, Tse CWS, Zee JST, Tsang OTY, Cheng VCC, Lau SKP, Woo PCY, Tsang DNC, Yuen KY. Transmission of Rat Hepatitis E Virus Infection to Humans in Hong Kong: A Clinical and Epidemiological Analysis. Hepatology 2021; 73:10-22. [PMID: 31960460 DOI: 10.1002/hep.31138] [Citation(s) in RCA: 140] [Impact Index Per Article: 35.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/15/2019] [Accepted: 12/23/2019] [Indexed: 12/13/2022]
Abstract
BACKGROUND AND AIMS Hepatitis E virus (HEV) variants causing human infection predominantly belong to HEV species A (HEV-A). HEV species C genotype 1 (HEV-C1) circulates in rats and is highly divergent from HEV-A. It was previously considered unable to infect humans, but the first case of human HEV-C1 infection was recently discovered in Hong Kong. The aim of this study is to further describe the features of this zoonosis in Hong Kong. APPROACH AND RESULTS We conducted a territory-wide prospective screening study for HEV-C1 infection over a 31-month period. Blood samples from 2,860 patients with abnormal liver function (n = 2,201) or immunosuppressive conditions (n = 659) were screened for HEV-C1 RNA. In addition, 186 captured commensal rats were screened for HEV-C1 RNA. Sequences of human-derived and rat-derived HEV-C1 isolates were compared. Epidemiological and clinical features of HEV-C1 infection were analyzed. HEV-C1 RNA was detected in 6/2,201 (0.27%) patients with hepatitis and 1/659 (0.15%) immunocompromised persons. Including the previously reported case, eight HEV-C1 infections were identified, including five in patients who were immunosuppressed. Three patients had acute hepatitis, four had persistent hepatitis, and one had subclinical infection without hepatitis. One patient died of meningoencephalitis, and HEV-C1 was detected in cerebrospinal fluid. HEV-C1 hepatitis was generally milder than HEV-A hepatitis. HEV-C1 RNA was detected in 7/186 (3.76%) rats. One HEV-C1 isolate obtained from a rat captured near the residences of patients was closely related to the major outbreak strain. CONCLUSIONS HEV-C1 is a cause of hepatitis E in humans in Hong Kong. Immunosuppressed individuals are susceptible to persistent HEV-C1 infection and extrahepatic manifestations. Subclinical HEV-C1 infection threatens blood safety. Tests for HEV-C1 are required in clinical laboratories.
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Affiliation(s)
- Siddharth Sridhar
- Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.,State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Hong Kong, China.,Carol Yu Centre for Infection, The University of Hong Kong, Hong Kong, China
| | - Cyril Chik-Yan Yip
- Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
| | - Shusheng Wu
- Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
| | - Nicholas Foo-Siong Chew
- Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
| | - Kit-Hang Leung
- Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
| | - Jasper Fuk-Woo Chan
- Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.,State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Hong Kong, China.,Carol Yu Centre for Infection, The University of Hong Kong, Hong Kong, China
| | - Pyrear Suhui Zhao
- Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
| | - Wan-Mui Chan
- Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
| | - Rosana Wing-Shan Poon
- Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
| | - Hoi-Wah Tsoi
- Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
| | - Jian-Piao Cai
- Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
| | - Helen Shuk-Ying Chan
- The Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The University of Hong Kong, Hong Kong, China
| | | | | | | | | | - Vincent Chi-Chung Cheng
- Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
| | - Susanna Kar-Pui Lau
- Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.,State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Hong Kong, China.,Carol Yu Centre for Infection, The University of Hong Kong, Hong Kong, China.,Tuen Mun Hospital, Hong Kong, China
| | - Patrick Chiu-Yat Woo
- Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.,State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Hong Kong, China.,Carol Yu Centre for Infection, The University of Hong Kong, Hong Kong, China.,Tuen Mun Hospital, Hong Kong, China
| | | | - Kwok-Yung Yuen
- Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.,State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Hong Kong, China.,Carol Yu Centre for Infection, The University of Hong Kong, Hong Kong, China.,Tuen Mun Hospital, Hong Kong, China
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Surveillance Study of Hepatitis E Virus (HEV) in Domestic and Wild Ruminants in Northwestern Italy. Animals (Basel) 2020; 10:ani10122351. [PMID: 33317114 PMCID: PMC7764585 DOI: 10.3390/ani10122351] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2020] [Revised: 12/06/2020] [Accepted: 12/08/2020] [Indexed: 02/07/2023] Open
Abstract
Simple Summary Hepatitis E virus (HEV) infection can cause both acute and chronic hepatitis in humans and represents an emerging public health concern worldwide. In developed countries, zoonotic transmission of HEV genotypes 3 and 4 is caused by ingestion of raw or undercooked meat of infected swine or wild boars, the main reservoirs of HEV. However, in the last few years, molecular and serological evidence seem to indicate that several other animal species may act as HEV host, including domestic and wild ruminants. In this study, serum and fecal specimens from sheep, goats, red deer, roe deer, chamois, and Alpine ibex collected in two northwestern Italian regions (Piemonte and Valle d’Aosta) were screened molecularly and serologically. With the exception of chamois, HEV antibodies were found both in the domestic and wild ruminant species investigated with the highest rates in sheep and goats. These findings demonstrate that wild also domestic ruminants may be implicated in the viral cycle transmission. Abstract In industrialized countries, increasing autochthonous infections of hepatitis E virus (HEV) are caused by zoonotic transmission of genotypes (Gts) 3 and 4, mainly through consumption of contaminated raw or undercooked pork meat. Although swine and wild boar are recognized as the main reservoir for Gt3 and Gt4, accumulating evidence indicates that other animal species, including domestic and wild ruminants, may harbor HEV. Herein, we screened molecularly and serologically serum and fecal samples from two domestic and four wild ruminant species collected in Valle d’Aosta and Piemonte regions (northwestern Italy. HEV antibodies were found in sheep (21.6%), goats (11.4%), red deer (2.6%), roe deer (3.1%), and in Alpine ibex (6.3%). Molecular screening was performed using different primer sets targeting highly conserved regions of hepeviruses and HEV RNA, although at low viral loads, was detected in four fecal specimens (3.0%, 4/134) collected from two HEV seropositive sheep herds. Taken together, the data obtained document the circulation of HEV in the geographical area assessed both in wild and domestic ruminants, but with the highest seroprevalence in sheep and goats. Consistently with results from other studies conducted in southern Italy, circulation of HEV among small domestic ruminants seems to occur more frequently than expected.
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Identification of Hepatitis E Virus in the Feces of Red Foxes ( Vulpes vulpes). Animals (Basel) 2020; 10:ani10101841. [PMID: 33050408 PMCID: PMC7601027 DOI: 10.3390/ani10101841] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2020] [Revised: 10/02/2020] [Accepted: 10/03/2020] [Indexed: 12/19/2022] Open
Abstract
Simple Summary Orthohepeviruses, commonly known as Hepatitis E virus (HEV), is a diverse virus group belonging to the family of Hepeviridae and is responsible for acute hepatitis in humans worldwide. These viruses show a relatively strict host specificity, e.g., rodent-related, avian-related, or even bat-related virus groups. However, similar (HEV-like) viruses have been identified in carnivores; some of them form a new genetically separated group, while others show a close evolutionary relationship with the rodent-related group, thus makes the strict host-specificity questionable and the classification of these new strains uncertain. Herein, we investigated feces of red foxes, the most widespread carnivore species worldwide, to identify the Hepatitis E virus and to ascertain their evolutionary origin via sequencing. The non-invasively collected fecal samples can provide information about the presence of viruses specific to the host and viruses derived from their prey as well. The virus we detected from our samples showed a very close relationship (91% identity) with rodent-related HEV described before from common voles, whilst a more distant relationship (85%) with fox-specific HEV strains was observed. Our results strongly support “the dietary-origin” of unclassified HEV-like strains described from various predator species. Abstract Orthohepeviruses (HEV) can infect a wide range of animals, showing a relatively strict host specificity; however, its zoonotic potential, natural transmission in the wildlife are less known. Several new HEV-like viruses have been identified in various animal species, including carnivores; however, the phylogenetic relationship among these viruses is poorly resolved, since some of them were known as rodent-related so far. The red fox, the most widespread carnivore worldwide, is a known reservoir of several viruses that transmit from wildlife to humans or domestic animals; they might have a defined role in the circulation of rodent-borne HEV. In this study, we performed a HEV survey by heminested RT-PCR (Reverse Transcription PCR) on red fox fecal samples to investigate the presence of HEV in red foxes living in natural conditions, and to explore the origin of the virus via phylogenetic analysis. Out of the 26 investigated samples, HEV RNA was identified in one sample. Following Sanger sequencing, the novel sequence displayed 91% identity on the nucleotide level with recently published European common vole-HEV derived from Microtus arvalis. In contrast, it shared 85% nucleotide similarity with HEV strains described previously in red foxes. Our results strongly support “the dietary-origin” of unclassified HEV-like strains described from predators that usually prey on rodents.
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Review of Hepatitis E Virus in Rats: Evident Risk of Species Orthohepevirus C to Human Zoonotic Infection and Disease. Viruses 2020; 12:v12101148. [PMID: 33050353 PMCID: PMC7600399 DOI: 10.3390/v12101148] [Citation(s) in RCA: 53] [Impact Index Per Article: 10.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2020] [Revised: 09/29/2020] [Accepted: 10/07/2020] [Indexed: 12/13/2022] Open
Abstract
Hepatitis E virus (HEV) (family Hepeviridae) is one of the most common human pathogens, causing acute hepatitis and an increasingly recognized etiological agent in chronic hepatitis and extrahepatic manifestations. Recent studies reported that not only are the classical members of the species Orthohepevirus A (HEV-A) pathogenic to humans but a genetically highly divergent rat origin hepevirus (HEV-C1) in species Orthohepevirus C (HEV-C) is also able to cause zoonotic infection and symptomatic disease (hepatitis) in humans. This review summarizes the current knowledge of hepeviruses in rodents with special focus of rat origin HEV-C1. Cross-species transmission and genetic diversity of HEV-C1 and confirmation of HEV-C1 infections and symptomatic disease in humans re-opened the long-lasting and full of surprises story of HEV in human. This novel knowledge has a consequence to the epidemiology, clinical aspects, laboratory diagnosis, and prevention of HEV infection in humans.
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