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Miao Z, Cao K, Wu X, Zhang C, Gao J, Chen Y, Sun Z, Ren X, Chen Y, Yang M, Chen C, Jiang D, Du Y, Lv X, Yang S. An outbreak of hepatitis E virus genotype 4d caused by consuming undercooked pig liver in a nursing home in Zhejiang Province, China. Int J Food Microbiol 2024; 417:110682. [PMID: 38626694 DOI: 10.1016/j.ijfoodmicro.2024.110682] [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: 11/05/2023] [Revised: 02/29/2024] [Accepted: 03/14/2024] [Indexed: 04/18/2024]
Abstract
Hepatitis E infection is typically caused by contaminated water or food. In July and August 2022, an outbreak of hepatitis E was reported in a nursing home in Zhejiang Province, China. Local authorities and workers took immediate actions to confirm the outbreak, investigated the sources of infection and routes of transmission, took measures to terminate the outbreak, and summarized the lessons learned. An epidemiological investigation was conducted on all individuals in the nursing home, including demographic information, clinical symptoms, history of dietary, water intake and contact. Stool and blood samples were collected from these populations for laboratory examinations. The hygiene environment of the nursing home was also investigated. A case-control study was conducted to identify the risk factors for this outbreak. Of the 722 subjects in the nursing home, 77 were diagnosed with hepatitis E, for an attack rate of 10.66 %. Among them, 18 (23.38 %, 18/77) individuals had symptoms such as jaundice, fever, and loss of appetite and were defined as the population with hepatitis E. The average age of people infected with hepatitis E virus (HEV) was 59.96 years and the attack rate of hepatitis E among women (12.02 %, 59/491) was greater than that among men (7.79 %, 18/231). The rate was the highest among caregivers (22.22 %, 32/144) and lowest among logistics personnel (6.25 %, 2/32); however, these differences were not statistically significant (P > 0.05). Laboratory sequencing results indicated that the genotype of this hepatitis E outbreak was 4d. A case-control study showed that consuming pig liver (odds ratio (OR) = 7.50; 95 % confidence interval [CI]: 3.84-16.14, P < 0.001) and consuming raw fruits and vegetables (OR = 5.92; 95 % CI: 1.74-37.13, P = 0.017) were risk factors for this outbreak of Hepatitis E. Moreover, a monitoring video showed that the canteen personnel did not separate raw and cooked foods, and pig livers were cooked for only 2 min and 10 s. Approximately 1 month after the outbreak, an emergency vaccination for HEV was administered. No new cases were reported after two long incubation periods (approximately 4 months). The outbreak of HEV genotype 4d was likely caused by consuming undercooked pig liver, resulting in an attack rate of 10.66 %. This was related to the rapid stir-frying cooking method and the hygiene habit of not separating raw and cooked foods.
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Affiliation(s)
- Ziping Miao
- Zhejiang Provincial Centre for Disease Control and Prevention, Hangzhou, China
| | - Kexin Cao
- Department of Emergency Medicine, Second Affiliated Hospital, Department of Epidemiology and Biostatistics, School of Public Health, The Key Laboratory of Intelligent Preventive Medicine of Zhejiang Province, Zhejiang University School of Medicine, Hangzhou, China
| | - Xiaoyue Wu
- Department of Emergency Medicine, Second Affiliated Hospital, Department of Epidemiology and Biostatistics, School of Public Health, The Key Laboratory of Intelligent Preventive Medicine of Zhejiang Province, Zhejiang University School of Medicine, Hangzhou, China
| | - Chenye Zhang
- Hangzhou Gongshu District Center for Disease Control and Prevention, Hangzhou, China
| | - Jian Gao
- Zhejiang Provincial Centre for Disease Control and Prevention, Hangzhou, China
| | - Yin Chen
- Zhejiang Provincial Centre for Disease Control and Prevention, Hangzhou, China
| | - Zhou Sun
- Hangzhou Center for Disease Control and Prevention, Hangzhou, China
| | - Xiaobin Ren
- Hangzhou Center for Disease Control and Prevention, Hangzhou, China
| | - Yijuan Chen
- Zhejiang Provincial Centre for Disease Control and Prevention, Hangzhou, China
| | - Mengya Yang
- Department of Emergency Medicine, Second Affiliated Hospital, Department of Epidemiology and Biostatistics, School of Public Health, The Key Laboratory of Intelligent Preventive Medicine of Zhejiang Province, Zhejiang University School of Medicine, Hangzhou, China
| | - Can Chen
- Department of Emergency Medicine, Second Affiliated Hospital, Department of Epidemiology and Biostatistics, School of Public Health, The Key Laboratory of Intelligent Preventive Medicine of Zhejiang Province, Zhejiang University School of Medicine, Hangzhou, China
| | - Daixi Jiang
- Department of Emergency Medicine, Second Affiliated Hospital, Department of Epidemiology and Biostatistics, School of Public Health, The Key Laboratory of Intelligent Preventive Medicine of Zhejiang Province, Zhejiang University School of Medicine, Hangzhou, China
| | - Yuxia Du
- Department of Emergency Medicine, Second Affiliated Hospital, Department of Epidemiology and Biostatistics, School of Public Health, The Key Laboratory of Intelligent Preventive Medicine of Zhejiang Province, Zhejiang University School of Medicine, Hangzhou, China
| | - Xin Lv
- Hangzhou Gongshu District Center for Disease Control and Prevention, Hangzhou, China.
| | - Shigui Yang
- Department of Emergency Medicine, Second Affiliated Hospital, Department of Epidemiology and Biostatistics, School of Public Health, The Key Laboratory of Intelligent Preventive Medicine of Zhejiang Province, Zhejiang University School of Medicine, Hangzhou, China.
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Cancela F, Rendon-Marin S, Quintero-Gil C, Houston DR, Gumbis G, Panzera Y, Pérez R, Arbiza J, Mirazo S. Modelling of Hepatitis E virus RNA-dependent RNA polymerase genotype 3 from a chronic patient and in silico interaction analysis by molecular docking with Ribavirin. J Biomol Struct Dyn 2023; 41:705-721. [PMID: 34861797 DOI: 10.1080/07391102.2021.2011416] [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] [Indexed: 01/04/2023]
Abstract
Hepatitis E Virus (HEV) infection is an emergent zoonotic disease, where chronic hepatitis E associated to solid organ transplant (SOT) recipients, related to genotype 3, is the clinical manifestation of major concern. In this setting, ribavirin (RBV) treatment is the only available therapy, though drug-resistant variants could emerge leading to a therapeutic failure. Crystallographic structures have not been reported for most of the HEV proteins, including the RNA-polymerase (RdRp). Therefore, the mechanism of action of RBV against HEV and the molecular interactions between this drug and RdRp are largely unknown. In this work, we aimed to model in silico the 3 D structure of a novel HEV3 RdRp (HEV_C1_Uy) from a chronically HEV infected-SOT recipient treated with RBV and to perform a molecular docking simulation between RBV triphosphate (RBVT), 7-methyl-guanosine-5'-triphosphate and the modelled protein. The models were generated using I-TASSER server and validated with multiple bioinformatics tools. The docking analysis were carried out with AutoDock Vina and LeDock software. We obtained a suitable model for HEV_C1_Uy (C-Score=-1.33, RMSD = 10.4 ± 4.6 Å). RBVT displayed a binding affinity of -7.6 ± 0.2 Kcal/mol by molecular docking, mediated by 6 hydrogen-bonds (Q195-O14, S198-O11, E257-O13, S260-O2, O3, S311-O11) between the finger's-palm-domains and a free binding energy of 31.26 ± 16.81 kcal/mol by molecular dynamics simulations. We identified the possible HEV RdRp interacting region for incoming nucleotides or analogs and provide novel insights that will contribute to better understand the molecular interactions of RBV and the enzyme and the mechanism of action of this antiviral drug.Communicated by Ramaswamy H. Sarma.
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Affiliation(s)
- Florencia Cancela
- Sección Virología, Facultad de Ciencias, Universidad de la República, Montevideo, Uruguay
| | - Santiago Rendon-Marin
- Grupo de Investigación en Ciencias Animales - GRICA, Facultad de Medicina Veterinaria y Zootecnia, Universidad Cooperativa de Colombia, sede Bucaramanga, Bucaramanga, Colombia
| | - Carolina Quintero-Gil
- Grupo de Investigación en Ciencias Animales - GRICA, Facultad de Medicina Veterinaria y Zootecnia, Universidad Cooperativa de Colombia, sede Bucaramanga, Bucaramanga, Colombia
| | - Douglas R Houston
- Institute of Quantitative Biology, Biochemistry and Biotechnology, The University of Edinburgh, Edinburgh, UK
| | - Gediminas Gumbis
- Institute of Quantitative Biology, Biochemistry and Biotechnology, The University of Edinburgh, Edinburgh, UK
| | - Yanina Panzera
- Sección Genética Evolutiva, Instituto de Biología, Facultad de Ciencias, Universidad de la República, Montevideo, Uruguay
| | - Ruben Pérez
- Sección Genética Evolutiva, Instituto de Biología, Facultad de Ciencias, Universidad de la República, Montevideo, Uruguay
| | - Juan Arbiza
- Sección Virología, Facultad de Ciencias, Universidad de la República, Montevideo, Uruguay
| | - Santiago Mirazo
- Sección Virología, Facultad de Ciencias, Universidad de la República, Montevideo, Uruguay.,Departamento de Bacteriología y Virología, Instituto de Higiene, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay
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Wang B, Tian D, Sooryanarain H, Mahsoub HM, Heffron CL, Hassebroek AM, Meng XJ. Two mutations in the ORF1 of genotype 1 hepatitis E virus enhance virus replication and may associate with fulminant hepatic failure. Proc Natl Acad Sci U S A 2022; 119:e2207503119. [PMID: 35969750 PMCID: PMC9407470 DOI: 10.1073/pnas.2207503119] [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: 04/30/2022] [Accepted: 07/16/2022] [Indexed: 11/18/2022] Open
Abstract
Hepatitis E virus (HEV) infection in pregnant women has a high incidence of developing fulminant hepatic failure (FHF) with significant mortality. Multiple amino acid changes in genotype 1 HEV (HEV-1) are reportedly linked to FHF clinical cases, but experimental confirmation of the roles of these changes in FHF is lacking. By utilizing the HEV-1 indicator replicon and infectious clone, we generated 11 HEV-1 single mutants, each with an individual mutation, and investigated the effect of these mutations on HEV replication and infection in human liver cells. We demonstrated that most of the mutations actually impaired HEV-1 replication efficiency compared with the wild type (WT), likely due to altered physicochemical properties and structural conformations. However, two mutations, A317T and V1120I, significantly increased HEV-1 replication. Notably, these two mutations simultaneously occurred in 100% of 21 HEV-1 variants from patients with FHF in Bangladesh. We further created an HEV-1 A317T/V1120I double mutant and found that it greatly enhanced HEV replication, which may explain the rapid viral replication and severe disease. Furthermore, we tested the effect of these FHF-associated mutations on genotype 3 HEV (HEV-3) replication and found that all the mutants had a reduced level of replication ability and infectivity, which is not unexpected due to distinct infection patterns between HEV-1 and HEV-3. Additionally, we demonstrated that these FHF-associated mutations do not appear to alter their sensitivity to ribavirin (RBV), suggesting that ribavirin remains a viable option for antiviral therapy for patients with FHF. The results have important implications for understanding the mechanism of HEV-1-associated FHF.
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Affiliation(s)
- Bo Wang
- Department of Biomedical Sciences and Pathobiology, Virginia–Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061
- Center for Emerging, Zoonotic and Arthropod-Borne Pathogens, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061
| | - Debin Tian
- Department of Biomedical Sciences and Pathobiology, Virginia–Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061
- Center for Emerging, Zoonotic and Arthropod-Borne Pathogens, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061
| | - Harini Sooryanarain
- Department of Biomedical Sciences and Pathobiology, Virginia–Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061
- Center for Emerging, Zoonotic and Arthropod-Borne Pathogens, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061
| | - Hassan M. Mahsoub
- Department of Biomedical Sciences and Pathobiology, Virginia–Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061
- Center for Emerging, Zoonotic and Arthropod-Borne Pathogens, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061
| | - C. Lynn Heffron
- Department of Biomedical Sciences and Pathobiology, Virginia–Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061
- Center for Emerging, Zoonotic and Arthropod-Borne Pathogens, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061
| | - Anna M. Hassebroek
- Department of Biomedical Sciences and Pathobiology, Virginia–Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061
- Center for Emerging, Zoonotic and Arthropod-Borne Pathogens, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061
| | - Xiang-Jin Meng
- Department of Biomedical Sciences and Pathobiology, Virginia–Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061
- Center for Emerging, Zoonotic and Arthropod-Borne Pathogens, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061
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Qashqari FS. Seroprevalence of Hepatitis E Virus Infection in Middle Eastern Countries: A Systematic Review and Meta-Analysis. Medicina (B Aires) 2022; 58:medicina58070905. [PMID: 35888624 PMCID: PMC9318471 DOI: 10.3390/medicina58070905] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2022] [Revised: 07/02/2022] [Accepted: 07/04/2022] [Indexed: 11/25/2022] Open
Abstract
Hepatitis E virus (HEV) is a hepatotropic virus that is a major public health concern worldwide. Autochthonous HEV is spread through oral feces in unsanitary environments, as well as vertical and, occasionally, blood transfusion. HEV is more common in developing countries, but it has recently become more widespread in developed countries as well. The Middle East (ME) has long been an endemic location for HEV infection. Therefore, the aim of this systematic review and meta-analysis was to assess the seroprevalence of anti-HEV antibodies in ME countries. The author systematically searched five databases, namely ScienceDirect, EMBASE, Scopus, PubMed, and Google Scholar, to identify English-language articles published on or before 25 April 2022. Comprehensive meta-analysis software was used for all statistical analyses (CMA, version 3, BioStat, Englewood, CO, USA). After quality control and exclusion of irrelevant studies, 80 studies were included in the qualitative synthesis and meta-analysis. A forest plot showed that the overall pooled seroprevalence of HEV infection in ME countries in the fixed-effect and random-effect models were 21.3% (95% CI: 0.209–0.216) and 11.8% (95% CI: 0.099–0.144), respectively. Furthermore, the findings showed a high level of heterogeneity (I2 = 98.733%) among the included studies. In both fixed-effect and random-effect models, the seroprevalence of HEV infection by country was high in Egypt as compared to other regions, at 35.0% (95% CI: 0.342–0.359), and 34.7% (95% CI: 0.153–0.611), respectively. The seroprevalence of HEV infection by country was high among pregnant women, at 47.9% (95% CI: 0.459–0.499) in the fixed-effect model, and in renal transplant recipients, at 30.8% (95% CI: 0.222–0.410) in the random-effect model. The seroprevalence of HEV infection varies by country and study population in the Middle East. More research is needed to determine the disease’s incidence, morbidity, and mortality in the region, where it is prevalent.
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Affiliation(s)
- Fadi S Qashqari
- Department of Microbiology, College of Medicine, Umm Al-Qura University, Makkah 24381, Saudi Arabia
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Marascio N, Rotundo S, Quirino A, Matera G, Liberto MC, Costa C, Russo A, Trecarichi EM, Torti C. Similarities, differences, and possible interactions between hepatitis E and hepatitis C viruses: Relevance for research and clinical practice. World J Gastroenterol 2022; 28:1226-1238. [PMID: 35431515 PMCID: PMC8968488 DOI: 10.3748/wjg.v28.i12.1226] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/05/2021] [Revised: 01/06/2022] [Accepted: 02/23/2022] [Indexed: 02/06/2023] Open
Abstract
Hepatitis E virus (HEV) and hepatitis C virus (HCV) are both RNA viruses with a tropism for liver parenchyma but are also capable of extrahepatic manifestations. Hepatitis E is usually a viral acute fecal-oral transmitted and self-limiting disease presenting with malaise, jaundice, nausea and vomiting. Rarely, HEV causes a chronic infection in immunocompromised persons and severe fulminant hepatitis in pregnant women. Parenteral HCV infection is typically asymptomatic for decades until chronic complications, such as cirrhosis and cancer, occur. Despite being two very different viruses in terms of phylogenetic and clinical presentations, HEV and HCV show many similarities regarding possible transmission through organ transplantation and blood transfusion, pathogenesis (production of antinuclear antibodies and cryoglobulins) and response to treatment with some direct-acting antiviral drugs. Although both HEV and HCV are well studied individually, there is a lack of knowledge about coinfection and its consequences. The aim of this review is to analyze current literature by evaluating original articles and case reports and to hypothesize some interactions that can be useful for research and clinical practice.
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Affiliation(s)
- Nadia Marascio
- Department of Health Sciences, Unit of Microbiology, University “Magna Graecia” of Catanzaro, Catanzaro 88100, Italy
| | - Salvatore Rotundo
- Department of Medical and Surgical Sciences, Unit of Infectious and Tropical Diseases, "Magna Graecia" University of Catanzaro, Catanzaro 88100, Italy
| | - Angela Quirino
- Department of Health Sciences, Unit of Microbiology, University “Magna Graecia” of Catanzaro, Catanzaro 88100, Italy
| | - Giovanni Matera
- Department of Health Sciences, Unit of Microbiology, University “Magna Graecia” of Catanzaro, Catanzaro 88100, Italy
| | - Maria Carla Liberto
- Department of Health Sciences, Unit of Microbiology, University “Magna Graecia” of Catanzaro, Catanzaro 88100, Italy
| | - Chiara Costa
- Department of Medical and Surgical Sciences, Unit of Infectious and Tropical Diseases, "Magna Graecia" University of Catanzaro, Catanzaro 88100, Italy
| | - Alessandro Russo
- Department of Medical and Surgical Sciences, Unit of Infectious and Tropical Diseases, "Magna Graecia" University of Catanzaro, Catanzaro 88100, Italy
| | - Enrico Maria Trecarichi
- Department of Medical and Surgical Sciences, Unit of Infectious and Tropical Diseases, "Magna Graecia" University of Catanzaro, Catanzaro 88100, Italy
| | - Carlo Torti
- Department of Medical and Surgical Sciences, Unit of Infectious and Tropical Diseases, "Magna Graecia" University of Catanzaro, Catanzaro 88100, Italy
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Cheung CKM, Wong SH, Law AWH, Law MF. Transfusion-transmitted hepatitis E: What we know so far? World J Gastroenterol 2022; 28:47-75. [PMID: 35125819 PMCID: PMC8793017 DOI: 10.3748/wjg.v28.i1.47] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/10/2021] [Revised: 07/16/2021] [Accepted: 12/22/2021] [Indexed: 02/06/2023] Open
Abstract
Hepatitis E virus (HEV) is a major cause of viral hepatitis globally. There is growing concern about transfusion-transmitted HEV (TT-HEV) as an emerging global health problem. HEV can potentially result in chronic infection in immunocompromised patients, leading to a higher risk of liver cirrhosis and even death. Between 0.0013% and 0.281% of asymptomatic blood donors around the world have HEV viremia, and 0.27% to 60.5% have anti-HEV immunoglobulin G. HEV is infectious even at very low blood concentrations of the virus. Immunosuppressed patients who develop persistent hepatitis E infection should have their immunosuppressant regimen reduced; ribavirin may be considered as treatment. Pegylated interferon can be considered in those who are refractory or intolerant to ribavirin. Sofosbuvir, a nucleotide analog, showed modest antiviral activity in some clinical studies but sustained viral response was not achieved. Therefore, rescue treatment remains an unmet need. The need for HEV screening of all blood donations remains controversial. Universal screening has been adopted in some countries after consideration of risk and resource availability. Various pathogen reduction methods have also been proposed to reduce the risk of TT-HEV. Future studies are needed to define the incidence of transmission through transfusion, their clinical features, outcomes and prognosis.
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Affiliation(s)
| | - Sunny Hei Wong
- Institute of Digestive Disease and Department of Medicine and Therapeutics, the Chinese University of Hong Kong, Hong Kong 852, China
- Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore 639798, Singapore
| | | | - Man Fai Law
- Medicine and Therapeutics, Prince of Wales Hospital, Hong Kong 852, China
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Cancela F, Noceti O, Arbiza J, Mirazo S. Structural aspects of hepatitis E virus. Arch Virol 2022; 167:2457-2481. [PMID: 36098802 PMCID: PMC9469829 DOI: 10.1007/s00705-022-05575-8] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2022] [Accepted: 06/04/2022] [Indexed: 12/14/2022]
Abstract
Hepatitis E virus (HEV) is a leading cause of acute hepatitis worldwide. Hepatitis E is an enterically transmitted zoonotic disease that causes large waterborne epidemic outbreaks in developing countries and has become an increasing public-health concern in industrialized countries. In this setting, the infection is usually acute and self-limiting in immunocompetent individuals, although chronic cases in immunocompromised patients have been reported, frequently associated with several extrahepatic manifestations. Moreover, extrahepatic manifestations have also been reported in immunocompetent individuals with acute HEV infection. HEV belongs to the alphavirus-like supergroup III of single-stranded positive-sense RNA viruses, and its genome contains three partially overlapping open reading frames (ORFs). ORF1 encodes a nonstructural protein with eight domains, most of which have not been extensively characterized: methyltransferase, Y domain, papain-like cysteine protease, hypervariable region, proline-rich region, X domain, Hel domain, and RNA-dependent RNA polymerase. ORF2 and ORF3 encode the capsid protein and a multifunctional protein believed to be involved in virion release, respectively. The novel ORF4 is only expressed in HEV genotype 1 under endoplasmic reticulum stress conditions, and its exact function has not yet been elucidated. Despite important advances in recent years, the biological and molecular processes underlying HEV replication remain poorly understood, primarily due to a lack of detailed information about the functions of the viral proteins and the mechanisms involved in host-pathogen interactions. This review summarizes the current knowledge concerning HEV proteins and their biological properties, providing updated detailed data describing their function and focusing in detail on their structural characteristics. Furthermore, we review some unclear aspects of the four proteins encoded by the ORFs, highlighting the current key information gaps and discussing potential novel experimental strategies for shedding light on those issues.
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Affiliation(s)
- Florencia Cancela
- grid.11630.350000000121657640Sección Virología, Facultad de Ciencias, Universidad de la República, Montevideo, Uruguay
| | - Ofelia Noceti
- grid.414402.70000 0004 0469 0889Programa Nacional de Trasplante Hepático y Unidad Docente Asistencial Centro Nacional de Tratamiento Hepatobiliopancreatico. Hospital Central de las Fuerzas Armadas, Montevideo, Uruguay
| | - Juan Arbiza
- grid.11630.350000000121657640Sección Virología, Facultad de Ciencias, Universidad de la República, Montevideo, Uruguay
| | - Santiago Mirazo
- grid.11630.350000000121657640Sección Virología, Facultad de Ciencias, Universidad de la República, Montevideo, Uruguay ,grid.11630.350000000121657640Departamento de Bacteriología y Virología, Instituto de Higiene, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay ,Av. Alfredo Navarro 3051, PC 11600 Montevideo, Uruguay
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Kupke P, Werner JM. Hepatitis E Virus Infection-Immune Responses to an Underestimated Global Threat. Cells 2021; 10:cells10092281. [PMID: 34571931 PMCID: PMC8468229 DOI: 10.3390/cells10092281] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2021] [Revised: 08/23/2021] [Accepted: 08/30/2021] [Indexed: 12/19/2022] Open
Abstract
Infection with the hepatitis E virus (HEV) is one of the main ubiquitous causes for developing an acute hepatitis. Moreover, chronification plays a predominant role in immunocompromised patients such as transplant recipients with more frequent severe courses. Unfortunately, besides reduction of immunosuppression and off-label use of ribavirin or pegylated interferon alfa, there is currently no specific anti-viral treatment to prevent disease progression. So far, research on involved immune mechanisms induced by HEV is limited. It is very difficult to collect clinical samples especially from the early phase of infection since this is often asymptomatic. Nevertheless, it is certain that the outcome of HEV-infected patients correlates with the strength of the proceeding immune response. Several lymphoid cells have been identified in contributing either to disease progression or achieving sustained virologic response. In particular, a sufficient immune control by both CD4+ and CD8+ T cells is necessary to prevent chronic viral replication. Especially the mechanisms underlying fulminant courses are poorly understood. However, liver biopsies indicate the involvement of cytotoxic T cells in liver damage. In this review, we aimed to highlight different parts of the lymphoid immune response against HEV and point out questions that remain unanswered regarding this underestimated global threat.
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Velavan TP, Pallerla SR, Johne R, Todt D, Steinmann E, Schemmerer M, Wenzel JJ, Hofmann J, Shih JWK, Wedemeyer H, Bock CT. Hepatitis E: An update on One Health and clinical medicine. Liver Int 2021; 41:1462-1473. [PMID: 33960603 DOI: 10.1111/liv.14912] [Citation(s) in RCA: 75] [Impact Index Per Article: 18.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/11/2020] [Revised: 03/09/2021] [Accepted: 04/08/2021] [Indexed: 12/12/2022]
Abstract
The hepatitis E virus (HEV) is one of the main causes of acute hepatitis and the de facto global burden is underestimated. HEV-related clinical complications are often undetected and are not considered in the differential diagnosis. Convincing findings from studies suggest that HEV is clinically relevant not only in developing countries but also in industrialized countries. Eight HEV genotypes (HEV-1 to HEV-8) with different human and animal hosts and other HEV-related viruses are in circulation. Transmission routes vary by genotype and location, with large waterborne outbreaks in developing countries and zoonotic food-borne infections in developed countries. An acute infection can be aggravated in pregnant women, organ transplant recipients, patients with pre-existing liver disease and immunosuppressed patients. HEV during pregnancy affects the fetus and newborn with an increased risk of vertical transmission, preterm and stillbirth, neonatal jaundice and miscarriage. Hepatitis E is associated with extrahepatic manifestations that include neurological disorders such as neuralgic amyotrophy, Guillain-Barré syndrome and encephalitis, renal injury and haematological disorders. The risk of transfusion-transmitted HEV is increasingly recognized in Western countries where the risk may be because of a zoonosis. RNA testing of blood components is essential to determine the risk of transfusion-transmitted HEV. There are currently no approved drugs or vaccines for HEV infections. This review focuses on updating the latest developments in zoonoses, screening and diagnostics, drugs in use and under development, and vaccines.
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Affiliation(s)
- Thirumalaisamy P Velavan
- Institute of Tropical Medicine, University of Tübingen, Tübingen, Germany
- Vietnamese-German Center for Medical Research, VG-CARE, Hanoi, Vietnam
- Faculty of Medicine, Duy Tan University, Da Nang, Vietnam
| | - Srinivas R Pallerla
- Institute of Tropical Medicine, University of Tübingen, Tübingen, Germany
- Vietnamese-German Center for Medical Research, VG-CARE, Hanoi, Vietnam
| | - Reimar Johne
- German Federal Institute for Risk Assessment, Berlin, 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
| | - Mathias Schemmerer
- Institute of Clinical Microbiology and Hygiene, National Consultant Laboratory for HAV and HEV, University Medical Center Regensburg, Regensburg, Germany
| | - Jürgen J Wenzel
- Institute of Clinical Microbiology and Hygiene, National Consultant Laboratory for HAV and HEV, University Medical Center Regensburg, Regensburg, Germany
| | - Jörg Hofmann
- Institute of Virology, Charité Universitätsmedizin Berlin, Labor Berlin-Charité-Vivantes GmbH, Berlin, Germany
| | | | - Heiner Wedemeyer
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
- German Center for Infection Research, Partner Hannover-Braunschweig, Braunschweig, Germany
| | - Claus-Thomas Bock
- Institute of Tropical Medicine, University of Tübingen, Tübingen, Germany
- Division of Viral Gastroenteritis and Hepatitis Pathogens and Enteroviruses, Department of Infectious Diseases, Robert Koch Institute, Berlin, Germany
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10
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López-Santaella T, Álvarez Y Muñoz T, Medeiros-Domingo M, Moreno-Espinosa S, Consuelo-Sánchez A, Muñoz-Hernández O, Sarmiento-Silva RE, Sotomayor-González A, Trujillo-Ortega ME, García-Hernández ME, Taboada-Ramírez BI, Arenas-Huertero F. Serological and molecular study of Hepatitis E virus in pediatric patients in Mexico. Ann Hepatol 2021; 19:295-301. [PMID: 31899127 DOI: 10.1016/j.aohep.2019.12.004] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/30/2019] [Revised: 11/27/2019] [Accepted: 12/04/2019] [Indexed: 02/04/2023]
Abstract
INTRODUCTION AND OBJECTIVES Cases of viral hepatitis reported in Mexico are typically identified as hepatitis A, B and C. However, unspecified cases are reported annually. Hepatitis E virus (HEV) is an emergent agent that causes a self-limiting infection that can evolve to chronic in immunosuppressed individuals. In Mexico, HEV genotype 2 is considered endemic, though it's the prevalence is not well known. Therefore, the present study was designed to determine the prevalence of HEV among patients at the "Hospital Infantil de Mexico Federico Gomez". MATERIALS AND METHODS The study included 99 patients, anti-HEV antibody (IgG and IgM) were detected by indirect ELISA and viral genome was identified using RT-PCR technique. Two PCR products of positive cases were sequenced. RESULTS ELISA results were positive in 3% and 6%, for IgG and IgM respectively, 54.5% prevalence was found by PCR. Low lymphocyte count (p<0.05) and malnutrition (p<0.005) were significant factors for high PCR prevalence and could increase the possibility of infection. Two samples were sequenced and confirmed the presence of HEV genotype 3. CONCLUSIONS This report reveals the incidence of HEV in pediatric patients in Mexico. Moreover, the identification of HEV genotype 3 in human samples suggests a potential zoonotic risk that requires further research.
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Affiliation(s)
- Tayde López-Santaella
- Laboratorio de Investigación en Patología Experimental, Hospital Infantil de México Federico Gómez, Ciudad de México, Mexico
| | - Teresa Álvarez Y Muñoz
- Laboratorio de Investigación en Patología Experimental, Hospital Infantil de México Federico Gómez, Ciudad de México, Mexico
| | - Mara Medeiros-Domingo
- Servicio de Nefrología, Hospital Infantil de México Federico Gómez, Ciudad de México, Mexico
| | | | | | - Onofre Muñoz-Hernández
- Dirección de Investigación, Hospital Infantil de México Federico Gómez, Ciudad de México, Mexico
| | - Rosa Elena Sarmiento-Silva
- Departamento de Microbiología e Inmunología, Facultad de Medicina Veterinaria y Zootecnia, Universidad Nacional Autónoma de México, Ciudad de México, Mexico.
| | - Alicia Sotomayor-González
- Departamento de Microbiología e Inmunología, Facultad de Medicina Veterinaria y Zootecnia, Universidad Nacional Autónoma de México, Ciudad de México, Mexico
| | - María Elena Trujillo-Ortega
- Departamento de Medicina y Zootecnia de Cerdos, Facultad de Medicina Veterinaria y Zootecnia, Universidad Nacional Autónoma de México, Ciudad de México, Mexico
| | - Montserrat Elemi García-Hernández
- Departamento de Microbiología e Inmunología, Facultad de Medicina Veterinaria y Zootecnia, Universidad Nacional Autónoma de México, Ciudad de México, Mexico
| | - Blanca Itzel Taboada-Ramírez
- Departamento de Genética del Desarrollo y Fisiología Molecular, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Mor. Mexico
| | - Francisco Arenas-Huertero
- Laboratorio de Investigación en Patología Experimental, Hospital Infantil de México Federico Gómez, Ciudad de México, Mexico
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11
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Fragkou PC, Moschopoulos CD, Karofylakis E, Kelesidis T, Tsiodras S. Update in Viral Infections in the Intensive Care Unit. Front Med (Lausanne) 2021; 8:575580. [PMID: 33708775 PMCID: PMC7940368 DOI: 10.3389/fmed.2021.575580] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2020] [Accepted: 02/02/2021] [Indexed: 12/15/2022] Open
Abstract
The advent of highly sensitive molecular diagnostic techniques has improved our ability to detect viral pathogens leading to severe and often fatal infections that require admission to the Intensive Care Unit (ICU). Viral infections in the ICU have pleomorphic clinical presentations including pneumonia, acute respiratory distress syndrome, respiratory failure, central or peripheral nervous system manifestations, and viral-induced shock. Besides de novo infections, certain viruses fall into latency and can be reactivated in both immunosuppressed and immunocompetent critically ill patients. Depending on the viral strain, transmission occurs either directly through contact with infectious materials and large droplets, or indirectly through suspended air particles (airborne transmission of droplet nuclei). Many viruses can efficiently spread within hospital environment leading to in-hospital outbreaks, sometimes with high rates of mortality and morbidity, thus infection control measures are of paramount importance. Despite the advances in detecting viral pathogens, limited progress has been made in antiviral treatments, contributing to unexpectedly high rates of unfavorable outcomes. Herein, we review the most updated data on epidemiology, common clinical features, diagnosis, pathogenesis, treatment and prevention of severe community- and hospital-acquired viral infections in the ICU settings.
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Affiliation(s)
- Paraskevi C. Fragkou
- 4th Department of Internal Medicine, Medical School, National and Kapodistrian University of Athens, “Attikon” University Hospital, Athens, Greece
| | - Charalampos D. Moschopoulos
- 4th Department of Internal Medicine, Medical School, National and Kapodistrian University of Athens, “Attikon” University Hospital, Athens, Greece
| | - Emmanouil Karofylakis
- 4th Department of Internal Medicine, Medical School, National and Kapodistrian University of Athens, “Attikon” University Hospital, Athens, Greece
| | - Theodoros Kelesidis
- Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, United States
| | - Sotirios Tsiodras
- 4th Department of Internal Medicine, Medical School, National and Kapodistrian University of Athens, “Attikon” University Hospital, Athens, Greece
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12
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Watari T, Tachibana T, Okada A, Nishikawa K, Otsuki K, Nagai N, Abe H, Nakano Y, Takagi S, Amano Y. A review of food poisoning caused by local food in Japan. J Gen Fam Med 2021; 22:15-23. [PMID: 33457151 PMCID: PMC7796784 DOI: 10.1002/jgf2.384] [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: 03/24/2020] [Revised: 08/14/2020] [Accepted: 09/21/2020] [Indexed: 12/19/2022] Open
Abstract
Increasingly popular worldwide, Japanese cuisine includes several raw preparations such as sashimi and sushi; however, limited information on food poisoning from Japanese local food is available in English literature. Without appropriate knowledge, physicians may underdiagnose traveler's diarrhea among people returning from Japan. To provide accurate information to primary care physicians worldwide, we conducted a narrative review on food poisoning research published in Japanese and English over the past four years, considering the frequency and clinical importance of various presentations.
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Affiliation(s)
- Takashi Watari
- Postgraduate Clinical Training CenterShimane University HospitalShimaneJapan
| | | | - Azusa Okada
- Faculty of MedicineShimane UniversityShimaneJapan
| | | | | | | | - Haruki Abe
- Faculty of MedicineShimane UniversityShimaneJapan
| | | | - Soshi Takagi
- Faculty of MedicineShimane UniversityShimaneJapan
| | - Yu Amano
- Faculty of MedicineShimane UniversityShimaneJapan
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13
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Bigna JJ, Modiyinji AF, Nansseu JR, Amougou MA, Nola M, Kenmoe S, Temfack E, Njouom R. Burden of hepatitis E virus infection in pregnancy and maternofoetal outcomes: a systematic review and meta-analysis. BMC Pregnancy Childbirth 2020; 20:426. [PMID: 32723309 PMCID: PMC7388479 DOI: 10.1186/s12884-020-03116-2] [Citation(s) in RCA: 31] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2019] [Accepted: 07/16/2020] [Indexed: 12/27/2022] Open
Abstract
BACKGROUND There is still a dearth of knowledge on the burden of HEV infection in the global population of pregnant women. Therefore, we conducted a systematic review and meta-analysis to estimate the global burden of HEV infection in pregnancy. METHODS We searched PubMed, Embase, Web of Knowledge, and Global Index Medicus to identify articles published until January 26, 2020. We considered cross-sectional, case-control, and cohort studies reporting the immunoglobulins M HEV seroprevalence in asymptomatic and symptomatic (jaundice or elevated transaminases) pregnant women or investigating the association between HEV infection and maternofoetal outcomes. We used a random-effects model to pool studies. This review was registered with PROSPERO, CRD42018093820. RESULTS For HEV prevalence estimates, we included 52 studies (11,663 pregnant women). The seroprevalence was 3.5% (95% confidence interval: 1.4-6.4) in asymptomatic women (most of whom from high endemic areas). The prevalence in symptomatic women was 49.6% (42.6-56.7) with data only from HEV high endemic countries. In the multivariable meta-regression model, the prevalence was higher in symptomatic women compared to asymptomatic (adjusted prevalence odds ratio [aPOR]: 1.76; 95%CI: 1.61-1.91) and decreased with increasing year of publication (by 10-year) (aPOR: 0.90; 95%CI: 0.84-0.96). The proportion of HEV vertical transmission was 36.9% (13.3-64.2). Risk of bias was low, moderate and high respectively in 12 (23%), 37 (70%), and 4 studies (7%) addressing HEV prevalence estimation. HEV infection was associated with maternal deaths (pooled OR 7.17; 3.32-15.47), low birth weight (OR: 3.23; 1.71-6.10), small for gestational age (OR: 3.63; 1.25-10.49), preterm < 32 weeks (OR: 4.18; 1.23-14.20), and preterm < 37 weeks (OR: 3.45; 2.32-5.13), stillbirth (OR: 2.61; 1.64-4.14), intrauterine deaths (OR: 3.07; 2.13-4.43), and not with miscarriage (OR: 1.74; 0.77-3.90). All studies which assessed the association between HEV infection and maternofoetal outcomes had a moderate risk of bias. CONCLUSIONS Findings from this study are suggestive of a high burden of HEV infection in pregnancy in high endemic countries, its association with poor maternofoetal outcomes, and a high rate of vertical transmission. This study supports the need for specific strategies to prevent exposure of pregnant women to HEV infection, especially in high endemic areas.
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Affiliation(s)
- Jean Joel Bigna
- Department of Epidemiology and Public Health, Centre Pasteur of Cameroon, P.O. Box 1274, Yaoundé, Cameroon.
| | - Abdou Fatawou Modiyinji
- Department of Virology, Centre Pasteur of Cameroon, Yaoundé, Cameroon
- Department of Animals Biology and Physiology, Faculty of Sciences, University of Yaoundé I, Yaoundé, Cameroon
| | - Jobert Richie Nansseu
- Department for the Control of Disease, Epidemics and Pandemics, Ministry of Public Health, Yaoundé, Cameroon
- Department of Public Health, Faculty of Medicine and Biomedical Sciences, University of Yaoundé I, Yaoundé, Cameroon
| | - Marie A Amougou
- Department of Virology, Centre Pasteur of Cameroon, Yaoundé, Cameroon
- Department of Biochemistry, Faculty of Sciences, University of Yaoundé I, Yaoundé, Cameroon
| | - Moise Nola
- Department of Animals Biology and Physiology, Faculty of Sciences, University of Yaoundé I, Yaoundé, Cameroon
| | - Sébastien Kenmoe
- Department of Virology, Centre Pasteur of Cameroon, Yaoundé, Cameroon
| | - Elvis Temfack
- Department of Internal Medicine, Douala General Hospital, Douala, Cameroon
| | - Richard Njouom
- Department of Virology, Centre Pasteur of Cameroon, Yaoundé, Cameroon
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14
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Lhomme S, Marion O, Abravanel F, Izopet J, Kamar N. Clinical Manifestations, Pathogenesis and Treatment of Hepatitis E Virus Infections. J Clin Med 2020; 9:E331. [PMID: 31991629 PMCID: PMC7073673 DOI: 10.3390/jcm9020331] [Citation(s) in RCA: 80] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2019] [Revised: 01/14/2020] [Accepted: 01/22/2020] [Indexed: 02/07/2023] Open
Abstract
Hepatitis E virus (HEV) is the most common cause of acute viral hepatitis throughout the world. Most infections are acute but they can become chronic in immunocompromised patients, such as solid organ transplant patients, patients with hematologic malignancy undergoing chemotherapy and those with a human immunodeficiency virus (HIV) infection. Extra-hepatic manifestations, especially neurological and renal diseases, have also been described. To date, four main genotypes of HEV (HEV1-4) were described. HEV1 and HEV2 only infect humans, while HEV3 and HEV4 can infect both humans and animals, like pigs, wild boar, deer and rabbits. The real epidemiology of HEV has been underestimated because most infections are asymptomatic. This review focuses on the recent advances in our understanding of the pathophysiology of acute HEV infections, including severe hepatitis in patients with pre-existing liver disease and pregnant women. It also examines the mechanisms leading to chronic infection in immunocompromised patients and extra-hepatic manifestations. Acute infections are usually self-limiting and do not require antiviral treatment. Conversely, a chronic HEV infection can be cleared by decreasing the dose of immunosuppressive drugs or by treating with ribavirin for 3 months. Nevertheless, new drugs are needed for those cases in which ribavirin treatment fails.
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Affiliation(s)
- Sébastien Lhomme
- Virology Laboratory, National Reference Center for Hepatitis E Virus, Toulouse Purpan University Hospital, 31300 Toulouse, France; (F.A.); (J.I.)
- INSERM UMR1043, Center for Pathophysiology of Toulouse Purpan, 31300 Toulouse, France;
- Université Toulouse III Paul Sabatier, 31330 Toulouse, France
| | - Olivier Marion
- INSERM UMR1043, Center for Pathophysiology of Toulouse Purpan, 31300 Toulouse, France;
- Université Toulouse III Paul Sabatier, 31330 Toulouse, France
- Department of Nephrology and Organs Transplantation, Toulouse Rangueil University Hospital, 31400 Toulouse, France
| | - Florence Abravanel
- Virology Laboratory, National Reference Center for Hepatitis E Virus, Toulouse Purpan University Hospital, 31300 Toulouse, France; (F.A.); (J.I.)
- INSERM UMR1043, Center for Pathophysiology of Toulouse Purpan, 31300 Toulouse, France;
- Université Toulouse III Paul Sabatier, 31330 Toulouse, France
| | - Jacques Izopet
- Virology Laboratory, National Reference Center for Hepatitis E Virus, Toulouse Purpan University Hospital, 31300 Toulouse, France; (F.A.); (J.I.)
- INSERM UMR1043, Center for Pathophysiology of Toulouse Purpan, 31300 Toulouse, France;
- Université Toulouse III Paul Sabatier, 31330 Toulouse, France
| | - Nassim Kamar
- INSERM UMR1043, Center for Pathophysiology of Toulouse Purpan, 31300 Toulouse, France;
- Université Toulouse III Paul Sabatier, 31330 Toulouse, France
- Department of Nephrology and Organs Transplantation, Toulouse Rangueil University Hospital, 31400 Toulouse, France
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15
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Aggarwal R, Goel A. Natural History, Clinical Manifestations, and Pathogenesis of Hepatitis E Virus Genotype 1 and 2 Infections. Cold Spring Harb Perspect Med 2019; 9:a032136. [PMID: 29735580 PMCID: PMC6601454 DOI: 10.1101/cshperspect.a032136] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Infection with genotype 1 or 2 hepatitis E virus (HEV) results primarily from human-to-human transmission through the fecal-oral route in low-resource countries. It presents primarily as "acute viral hepatitis" syndrome, usually a self-limiting illness. A few cases progress to acute liver failure, a serious illness with high fatality. Clinical disease is infrequent among children. Infection during pregnancy is associated with a higher risk of symptomatic disease, severe liver injury, and mortality. Severe disease is also encountered in persons with preexisting chronic liver disease. Some cases have associated extrahepatic features, particularly acute pancreatitis and neurological manifestations. Chronic infection appears to be extremely infrequent with these HEV genotypes. The exact pathogenesis of liver injury remains unknown, although the host immune response appears to be important for viral clearance as well as for induction of liver injury. Hormonal and immune factors appear to be responsible for the severe disease during pregnancy.
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Affiliation(s)
- Rakesh Aggarwal
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226014, India
| | - Amit Goel
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226014, India
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16
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Wang T, Cui D, Chen S, Xu X, Sun C, Dai Y, Cheng J. Analysis of clinical characteristics and S gene sequences in chronic asymptomatic HBV carriers with low-level HBsAg. Clin Res Hepatol Gastroenterol 2019; 43:179-189. [PMID: 30293895 DOI: 10.1016/j.clinre.2018.08.015] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/25/2018] [Revised: 08/20/2018] [Accepted: 08/22/2018] [Indexed: 02/04/2023]
Abstract
BACKGROUND During the natural hepatitis B virus (HBV) infection process, some infected subjects are characterized by a sustained low serum HBV surface antigen (HBsAg) expression level. Most members in this population are chronic asymptomatic HBV carriers (ASCs). To elucidate the mechanism underlying low-level HBsAg expression in ASCs, we sequenced the HBV S gene in these patients to reveal specific sequence characteristics. METHODS Overall, 1308 cases of chronic ASCs were grouped according to their HBsAg serum expression levels (10 IU/mL). The clinical characteristics of the population were analysed in detail. The HBV S gene was sequenced from 276 ASC cases with low-level HBsAg expression. Additionally, 100 of 1032 ASC cases with high-level HBsAg expression were randomly selected for HBV S gene sequencing based on age matching according to the low-level HBsAg group. A comparative analysis was conducted with the HBV S gene sequences from ASCs with low HBsAg expression and the HBV reference S gene sequences from ASCs with high HBsAg expression. RESULTS The population with low-level HBsAg expression displayed the following primary clinical characteristics: mostly chronic asymptomatic HBV carriers, older age (mean age 55.09 years), HBsAg/anti-HBe/anti-HBc (core) positivity as the main serological pattern (97.1%), low HBV DNA replication (1.32 ± 1.60 log10 IU/mL), a low HBV-DNA positive rate (45.65%) and primarily genotype B (82.54%) and serotype adw (84.13%). The comparative analysis of the HBV S gene sequences from ASCs with low-level HBsAg showed significant mutations (including co-mutations) on both sides of the main hydrophilic region (MHR). CONCLUSION Significant mutations in multiple regions and at multiple sites (including co-mutations) on both sides of the MHR may be one cause of the low HBsAg expression level in this population.
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Affiliation(s)
- Tong Wang
- Faculty of Graduate Studies, Bengbu Medical College, Bengbu 233000, PR China; Department of Clinical Research, The 117th Hospital of PLA, Hangzhou 310013, PR China; Faculty of Graduate Studies, Jiangsu University, Zhenjiang 212013, PR China.
| | - Dawei Cui
- Department of Laboratory Medicine, Key Laboratory of Clinical In Vitro Diagnostic Techniques of Zhejiang Province, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, PR China; Faculty of Graduate Studies, Jiangsu University, Zhenjiang 212013, PR China.
| | - Shaoming Chen
- Department of Clinical Research, The 117th Hospital of PLA, Hangzhou 310013, PR China; Faculty of Graduate Studies, Jiangsu University, Zhenjiang 212013, PR China.
| | - Xujian Xu
- Department of Biotechnology, The University of Tokyo, Tokyo 1138656, Japan; Faculty of Graduate Studies, Jiangsu University, Zhenjiang 212013, PR China.
| | - Changgui Sun
- Department of Clinical Research, The 117th Hospital of PLA, Hangzhou 310013, PR China; Faculty of Graduate Studies, Jiangsu University, Zhenjiang 212013, PR China.
| | - Yuzhu Dai
- Department of Clinical Research, The 117th Hospital of PLA, Hangzhou 310013, PR China; Department of Laboratory Medicine, Key Laboratory of Clinical In Vitro Diagnostic Techniques of Zhejiang Province, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, PR China.
| | - Jun Cheng
- Department of Clinical Research, The 117th Hospital of PLA, Hangzhou 310013, PR China; Faculty of Graduate Studies, Jiangsu University, Zhenjiang 212013, PR China.
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17
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Haffar S, Shalimar, Kaur RJ, Wang Z, Prokop LJ, Murad MH, Bazerbachi F. Acute liver failure caused by hepatitis E virus genotype 3 and 4: A systematic review and pooled analysis. Liver Int 2018; 38:1965-1973. [PMID: 29675889 DOI: 10.1111/liv.13861] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/02/2018] [Accepted: 04/03/2018] [Indexed: 02/13/2023]
Abstract
BACKGROUND & AIMS Acute liver failure caused by hepatitis E virus genotype 3 and 4 has been rarely described. Because of the presence of a short golden therapeutic window in patients with viral acute liver failure from other causes, it is possible that early recognition and treatment might reduce the morbidity and mortality. We performed a systematic review and pooled analysis of acute liver failure caused by hepatitis E virus genotype 3 and 4. METHODS Two reviewers appraised studies after searching multiple databases on June 12th, 2017. Appropriate tests were used to compare hepatitis E virus genotype 3 vs 4, suspected vs confirmed genotypes, hepatitis E virus-RNA positive vs negative, and to discern important mortality risk factors. RESULTS We identified 65 patients, with median age 58 years (range: 3-79), and a male to female ratio of 1.2:1. The median bilirubin, ALT, AST and alkaline phosphatase (expressed by multiplication of the upper limit of normal) levels were 14.8, 45.3, 34.8 and 1.63 respectively. Antihepatitis E virus IgG, antihepatitis E virus IgM and hepatitis E virus-RNA were positive in 84%, 91% and 86% of patients respectively. The median interval from symptoms onset to acute liver failure was 23 days, and 16 patients underwent liver transplantation. Final outcome was reported in 58 patients and mortality was 46%. Age was a predictor of poor prognosis in multivariate analysis. No important differences were found between patients infected with genotype 3 vs 4, patients with confirmed vs suspected genotypes, or patients with positive vs negative RNA. CONCLUSION Acute liver failure caused by hepatitis E virus genotype 3 and 4 is rare, similar between genotypes, occurs commonly in middle-aged/elderly patients and has a very high mortality. Age is predictive of poor prognosis in multivariate analysis.
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Affiliation(s)
- Samir Haffar
- Digestive center for diagnosis and treatment, Damascus, Syrian Arab Republic
| | - Shalimar
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India
| | - Ravinder J Kaur
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
| | - Zhen Wang
- Robert D and Patricia E Kern Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, MN, USA
| | - Larry J Prokop
- Library Public Services, Mayo Clinic, Rochester, MN, USA
| | - Mohammad H Murad
- Robert D and Patricia E Kern Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, MN, USA
| | - Fateh Bazerbachi
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
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18
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Smith DB, Simmonds P. Classification and Genomic Diversity of Enterically Transmitted Hepatitis Viruses. Cold Spring Harb Perspect Med 2018; 8:a031880. [PMID: 29530950 PMCID: PMC6120691 DOI: 10.1101/cshperspect.a031880] [Citation(s) in RCA: 66] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
Hepatitis A virus (HAV) and hepatitis E virus (HEV) are significant human pathogens and are responsible for a substantial proportion of cases of severe acute hepatitis worldwide. Genetically, both viruses are heterogeneous and are classified into several genotypes that differ in their geographical distribution and risk group association. There is, however, little evidence that variants of HAV or HEV differ antigenically or in their propensity to cause severe disease. Genetically more divergent but primarily hepatotropic variants of both HAV and HEV have been found in several mammalian species, those of HAV being classified into eight species within the genus Hepatovirus in the virus family Picornaviridae. HEV is classified as a member of the species Orthohepevirus A in the virus family Hepeviridae, a species that additionally contains viruses infecting pigs, rabbits, and a variety of other mammalian species. Other species (Orthohepevirus B-D) infect a wide range of other mammalian species including rodents and bats.
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Affiliation(s)
- Donald B Smith
- Centre for Immunity, Infection and Evolution, University of Edinburgh, Edinburgh EH9 3JT, United Kingdom
- Nuffield Department of Medicine, University of Oxford, Oxford OX1 3SY, United Kingdom
| | - Peter Simmonds
- Nuffield Department of Medicine, University of Oxford, Oxford OX1 3SY, United Kingdom
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19
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Parvez MK, Subbarao N. Molecular Analysis and Modeling of Hepatitis E Virus Helicase and Identification of Novel Inhibitors by Virtual Screening. BIOMED RESEARCH INTERNATIONAL 2018; 2018:5753804. [PMID: 30246023 PMCID: PMC6136533 DOI: 10.1155/2018/5753804] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/19/2018] [Accepted: 08/07/2018] [Indexed: 12/20/2022]
Abstract
The hepatitis E virus- (HEV-) helicase as a novel drug-target was evaluated. While cell culture model was used for mutational characterization of helicase, in silico protein modeling and virtual screening were employed to identify helicase inhibitors. None of the saturation mutant replicons significantly affected RNA replication. Notably, mutants encompassing the Walker motifs replicated as wild-type, showing indispensability of nucleotides conservation in viability compared to known criticality of amino acids. A 3D modeling of HEV-helicase and screening of a compound dataset identified ten most promising inhibitors with drug likeness, notably, JFD02650, RDR03130, and HTS11136 that interacted with Walker A residues Gly975, Gly978, Ser979, and Gly980. Our model building and virtual identification of novel helicase inhibitors warrant further studies towards developing anti-HEV drugs.
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Affiliation(s)
- Mohammad K. Parvez
- Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia
| | - Naidu Subbarao
- School of Computational and Integrative Sciences, Jawaharlal Nehru University, New Delhi, India
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20
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Substitution of amino acid residue V1213 in the helicase domain of the genotype 3 hepatitis E virus reduces virus replication. Virol J 2018; 15:32. [PMID: 29422085 PMCID: PMC5806379 DOI: 10.1186/s12985-018-0943-5] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2017] [Accepted: 02/01/2018] [Indexed: 12/17/2022] Open
Abstract
Background Genotype 3 hepatitis E virus (HEV) infection is generally associated with mild disease. However, recently eight genotype 3 HEV isolates were identified from patients with severe hepatitis. Importantly, three mutations (S605P, I978V and V1213A) in these genotype 3 isolates were found to be typical of genotype 4 HEV, which is sometime associated with more severe hepatitis. Therefore in this study we seek to determine if these unique mutations contribute to enhanced virus replication and thus potentially severe disease. Methods In the lack of an efficient cell culture system to study the effect of mutations on HEV replication, we developed a genotype 3 HEV replicon with Renilla luciferase (Rluc) as reporter and subsequently used it to construct numerous mutants, including swMu-1 (V1213A), swMu-2 (Q1246H), swMu-3 (V1213A and Q1246H), swMu-4 (S605P and I978V), and swMu-5 (V1213A, S605P and I978V). RNA transcripts from mutant replicons were transfected into Huh7 S10–3 liver cells to measure the effect of mutations on HEV replication efficiency. Results The results showed that the V1213A mutant had the highest reduction in HEV replication efficiency than other mutants. The V1213A and S605P + I978V mutations have a cumulative, if not synergistic, effect on HEV replication. The Q1246H mutant decreased HEV replication compared to the wild-type HEV Rluc replicon but replicated better than the V1213A mutant. The amino acid residue V1213 favors the replication of both genotypes 3 and 4 HEV strains, but not genotype 1 HEV. Conclusion The results suggested that the V1213A mutation reduced HEV replication, but is likely not associated with the reported severe hepatitis caused by genotype 3 HEV isolates containing this mutation.
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Ishida S, Matsuura K, Yoshizumi S, Miyoshi M, Sugisawa T, Tanida M, Okano M. Hepatitis E outbreak at a nursing home for aged people in Hokkaido, Japan, between February and March 2016. J Clin Virol 2018; 101:23-28. [PMID: 29414183 DOI: 10.1016/j.jcv.2018.01.009] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2017] [Revised: 01/15/2018] [Accepted: 01/20/2018] [Indexed: 12/28/2022]
Abstract
BACKGROUND Infection with hepatitis E virus (HEV) genotypes 3 and 4 are usually asymptomatic but can occasionally result in life-threatening acute hepatitis. To date, only sporadic cases together with a few outbreaks have been documented. Seroprevalence studies with assays for the detection of HEV IgG antibodies, suggest that HEV is more prevalent than previously thought, even in non-endemic regions. OBJECTIVES The aim of this study was to characterize an outbreak of hepatitis E (HE) in a nursing home for aged people between February and March 2016. STUDY DESIGN After the identification of two cases living in the same nursing home, the presence of antibodies against HEV and HEV RNA were examined in serum samples collected from the other residents and staff members to identify any additional cases. An epidemiological investigation was also carried out. RESULTS Only 4 patients showed mild symptoms such as anorexia, abdominal pain and fatigue. Among the 125 persons tested, 28 residents and one dietitian were confirmed positive for anti-HEV IgA or IgM antibodies, and/or HEV RNA. Eight samples had only IgG antibodies. Finally, 22 cases were notified with HE on the basis of the presence of IgA antibodies. All HEV isolates obtained were 99.8-100% identical and belonged to genotype 3. CONCLUSION HEV infections seem to be under-reported or underestimated possibly due to cases being generally asymptomatic. Testing for the presence of both anti-HEV antibodies and HEV RNA would be beneficial for both the comprehensive diagnosis of HE infections and the prevention of further infections.
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Affiliation(s)
| | - Kaori Matsuura
- Asahikawa City Center of Public Health, Asahikawa, Japan
| | | | | | - Takahisa Sugisawa
- Asahikawa City Center of Public Health, Asahikawa, Japan; Kushiro Center of Public Health, Kushiro, Japan
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Nan Y, Wu C, Zhao Q, Zhou EM. Zoonotic Hepatitis E Virus: An Ignored Risk for Public Health. Front Microbiol 2017; 8:2396. [PMID: 29255453 PMCID: PMC5723051 DOI: 10.3389/fmicb.2017.02396] [Citation(s) in RCA: 49] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2017] [Accepted: 11/20/2017] [Indexed: 12/27/2022] Open
Abstract
Hepatitis E virus (HEV) is a quasi-enveloped, single-stranded positive-sense RNA virus. HEV belongs to the family Hepeviridae, a family comprised of highly diverse viruses originating from various species. Since confirmation of HEV's zoonosis, HEV-induced hepatitis has been a public health concern both for developing and developed countries. Meanwhile, the demonstration of a broad host range for zoonotic HEV suggests the existence of a variety of transmission routes that could lead to human infection. Moreover, anti-HEV antibody serosurveillance worldwide demonstrates a higher than expected HEV prevalence rate that conflicts with the rarity and sporadic nature of reported acute hepatitis E cases. In recent years, chronic HEV infection, HEV-related acute hepatic failure, and extrahepatic manifestations caused by HEV infection have been frequently reported. These observations suggest a significant underestimation of the number and complexity of transmission routes previously predicted to cause HEV-related disease, with special emphasis on zoonotic HEV as a public health concern. Significant research has revealed details regarding the virology and infectivity of zoonotic HEV in both humans and animals. In this review, the discovery of HEV zoonosis, recent progress in our understanding of the zoonotic HEV host range, and classification of diverse HEV or HEV-like isolates from various hosts are reviewed in a historic context. Ultimately, this review focuses on current understanding of viral pathogenesis and cross-species transmission of zoonotic HEV. Moreover, host factors and viral determinants influencing HEV host tropism are discussed to provide new insights into HEV transmission and prevalence mechanisms.
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Affiliation(s)
- Yuchen Nan
- Department of Preventive Veterinary Medicine, College of Veterinary Medicine, Northwest A&F University, Xianyang, China
- Scientific Observing and Experimental Station of Veterinary Pharmacology and Diagnostic Technology, Ministry of Agriculture, Xianyang, China
| | - Chunyan Wu
- Department of Preventive Veterinary Medicine, College of Veterinary Medicine, Northwest A&F University, Xianyang, China
- Scientific Observing and Experimental Station of Veterinary Pharmacology and Diagnostic Technology, Ministry of Agriculture, Xianyang, China
| | - Qin Zhao
- Department of Preventive Veterinary Medicine, College of Veterinary Medicine, Northwest A&F University, Xianyang, China
- Scientific Observing and Experimental Station of Veterinary Pharmacology and Diagnostic Technology, Ministry of Agriculture, Xianyang, China
| | - En-Min Zhou
- Department of Preventive Veterinary Medicine, College of Veterinary Medicine, Northwest A&F University, Xianyang, China
- Scientific Observing and Experimental Station of Veterinary Pharmacology and Diagnostic Technology, Ministry of Agriculture, Xianyang, China
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Prost S, Crossan CL, Dalton HR, De Man RA, Kamar N, Selves J, Dhaliwal C, Scobie L, Bellamy COC. Detection of viral hepatitis E in clinical liver biopsies. Histopathology 2017; 71:580-590. [DOI: 10.1111/his.13266] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2017] [Revised: 05/11/2017] [Accepted: 05/20/2017] [Indexed: 12/20/2022]
Affiliation(s)
- Sandrine Prost
- Department of Pathology; Royal Infirmary of Edinburgh; Edinburgh UK
| | - Claire L Crossan
- Department of Biological and Biomedical Sciences; Glasgow Caledonian University; Glasgow UK
| | - Harry R Dalton
- European Centre for Environment and Human Health; University of Exeter; Exeter UK
| | - Robert A De Man
- Department of Gastroenterology and Hepatology; Erasmus Medical Center; Rotterdam the Netherlands
| | - Nassim Kamar
- Department of Nephrology and Organ Transplantation; Université Paul Sabatier; Toulouse France
| | - Janick Selves
- Centre de Recherche en Cancérologie de Toulouse; Department of Pathology; Centre Hospitalier Universitaire de Toulouse; Toulouse France
| | | | - Linda Scobie
- Department of Biological and Biomedical Sciences; Glasgow Caledonian University; Glasgow UK
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Parvez MK. The hepatitis E virus nonstructural polyprotein. Future Microbiol 2017; 12:915-924. [PMID: 28686042 DOI: 10.2217/fmb-2017-0016] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2017] [Accepted: 04/24/2017] [Indexed: 12/19/2022] Open
Abstract
Hepatitis E virus (HEV) is a globally important pathogen of acute and chronic hepatitis in humans. The HEV ORF1 gene encodes a nonstructural polyprotein, essential for RNA replication and virus infectivity. Expression and processing of ORF1 polyprotein are shown in prokaryotic and eukaryotic systems, however, its proteolysis into individual proteins is still debated. While molecular or biochemical characterization of methyltransferase, protease, hypervariable region, helicase and RNA polymerase domains in ORF1 has been achieved, the role of the X and Y domains in the HEV life cycle has only been demonstrated very recently. Clinically, detection of a number of ORF1 mutants in infected patients is implicated in disease severity, mortality and drug nonresponse. Moreover, several artificial lethal mutations in ORF1 offer a potential basis for developing live-attenuated vaccines for HEV. This article intends to present the molecular and clinical updates on the HEV ORF1 polyprotein.
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Affiliation(s)
- Mohammad Khalid Parvez
- Department of Pharmacognosy, King Saud University College of Pharmacy, Riyadh 11451, Saudi Arabia
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25
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26
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Wilhelm B, Fazil A, Rajić A, Houde A, McEwen SA. Risk Profile of Hepatitis E Virus from Pigs or Pork in Canada. Transbound Emerg Dis 2016; 64:1694-1708. [PMID: 27718330 DOI: 10.1111/tbed.12582] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2016] [Indexed: 12/17/2022]
Abstract
The role and importance of pigs and pork as sources of zoonotic hepatitis E virus (HEV) has been debated in Canada and abroad for over 20 years. To further investigate this question, we compiled data to populate a risk profile for HEV in pigs or pork in Canada. We organized the risk profile (RP) using the headings prescribed for a foodborne microbial risk assessment and used research synthesis methods and inputs wherever possible in populating the fields of this RP. A scoping review of potential public health risks of HEV, and two Canadian field surveys sampling finisher pigs, and retail pork chops and pork livers, provided inputs to inform this RP. We calculated summary estimates of prevalence using the Comprehensive Meta-analysis 3 software, employing the method of moments. Overall, we found the incidence of sporadic locally acquired hepatitis E in Canada, compiled from peer-reviewed literature or from diagnosis at the National Microbiology Laboratory to be low relative to other non-endemic countries. In contrast, we found the prevalence of detection of HEV RNA in pigs and retail pork livers, to be comparable to that reported in the USA and Europe. We drafted risk categories (high/medium/low) for acquiring clinical hepatitis E from exposure to pigs or pork in Canada and hypothesize that the proportion of the Canadian population at high risk from either exposure is relatively small.
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Affiliation(s)
- B Wilhelm
- Ontario Veterinary College, University of Guelph, Guelph, Ontario, Canada
| | - A Fazil
- Laboratory for Foodborne Zoonoses, Public Health Agency of Canada, Guelph, Ontario, Canada
| | - A Rajić
- Ontario Veterinary College, University of Guelph, Guelph, Ontario, Canada
| | - A Houde
- Food Research and Development Centre, Agriculture and Agri-Food Canada, St-Hyacinthe, Québec, Canada
| | - S A McEwen
- Ontario Veterinary College, University of Guelph, Guelph, Ontario, Canada
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Lhomme S, Marion O, Abravanel F, Chapuy-Regaud S, Kamar N, Izopet J. Hepatitis E Pathogenesis. Viruses 2016; 8:E212. [PMID: 27527210 PMCID: PMC4997574 DOI: 10.3390/v8080212] [Citation(s) in RCA: 68] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2016] [Revised: 07/22/2016] [Accepted: 07/27/2016] [Indexed: 02/08/2023] Open
Abstract
Although most hepatitis E virus (HEV) infections are asymptomatic, some can be severe, causing fulminant hepatitis and extra-hepatic manifestations, including neurological and kidney injuries. Chronic HEV infections may also occur in immunocompromised patients. This review describes how our understanding of the pathogenesis of HEV infection has progressed in recent years.
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Affiliation(s)
- Sébastien Lhomme
- INSERM, UMR1043, Department of Virology, CHU Purpan, Université Paul Sabatier, 31000 Toulouse, France.
| | - Olivier Marion
- INSERM, UMR1043, Department of Virology, CHU Purpan, Université Paul Sabatier, 31000 Toulouse, France.
- INSERM, UMR1043, Department of Nephrology, Dialysis and Organ Transplantation, CHU Rangueil, Université Paul Sabatier, 31000 Toulouse, France.
| | - Florence Abravanel
- INSERM, UMR1043, Department of Virology, CHU Purpan, Université Paul Sabatier, 31000 Toulouse, France.
| | - Sabine Chapuy-Regaud
- INSERM, UMR1043, Department of Virology, CHU Purpan, Université Paul Sabatier, 31000 Toulouse, France.
| | - Nassim Kamar
- INSERM, UMR1043, Department of Nephrology, Dialysis and Organ Transplantation, CHU Rangueil, Université Paul Sabatier, 31000 Toulouse, France.
| | - Jacques Izopet
- INSERM, UMR1043, Department of Virology, CHU Purpan, Université Paul Sabatier, 31000 Toulouse, France.
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Smith DB, Ijaz S, Tedder RS, Hogema B, Zaaijer HL, Izopet J, Bradley-Stewart A, Gunson R, Harvala H, Kokki I, Simmonds P. Variability and pathogenicity of hepatitis E virus genotype 3 variants. J Gen Virol 2015; 96:3255-3264. [PMID: 26282123 PMCID: PMC4806580 DOI: 10.1099/jgv.0.000264] [Citation(s) in RCA: 53] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022] Open
Abstract
Infection with hepatitis E virus (HEV) can be clinically inapparent or produce symptoms and signs of hepatitis of varying severity and occasional fatality. This variability in clinical outcomes may reflect differences in host susceptibility or the presence of virally encoded determinants of pathogenicity. Analysis of complete genome sequences supports the division of HEV genotype 3 (HEV-3) variants into three major clades: 3ra comprising HEV isolates from rabbits, and 3efg and 3abchij comprising the corresponding named subtypes derived from humans and pigs. Using this framework, we investigated associations between viral genetic variability of HEV-3 in symptomatic and asymptomatic infections by comparing HEV-3 subgenomic sequences previously obtained from blood donors with those from patients presenting with hepatitis in the UK (54 blood donors, 148 hepatitis patients), the Netherlands (38 blood donors, 119 hepatitis patients), France (24 blood donors, 55 hepatitis patients) and Germany (14 blood donors, 36 hepatitis patients). In none of these countries was evidence found for a significant association between virus variants and patient group (P>0.05 Fisher's exact test). Furthermore, within a group of 123 patients in Scotland with clinically apparent HEV infections, we found no evidence for an association between variants of HEV-3 and disease severity or alanine aminotransferase level. The lack of detectable virally encoded determinants of disease outcomes in HEV-3 infection implies a more important role for host factors in its clinical phenotype.
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Affiliation(s)
- Donald B Smith
- University of Edinburgh, CIIE, Ashworth Laboratories, King's Buildings, Edinburgh EH9 3FL, UK
| | - Samreen Ijaz
- Blood Borne Virus Unit, Virus Reference Department, MS-Colindale, Public Health England, London NW9 5EQ, UK
| | - Richard S Tedder
- Blood Borne Virus Unit, Virus Reference Department, MS-Colindale, Public Health England, London NW9 5EQ, UK.,University College London, Gower Street, London WC1E 6BT, UK
| | - Boris Hogema
- Department of Blood-borne Infections, Sanquin Research, PO Box 9190, 1006 AD Amsterdam, The Netherlands
| | - Hans L Zaaijer
- Department of Blood-borne Infections, Sanquin Research, PO Box 9190, 1006 AD Amsterdam, The Netherlands
| | - Jacques Izopet
- Institut National de la Sante et de la Recherche Medicale Unite 1043, Toulouse, France
| | | | - Rory Gunson
- West of Scotland Specialist Virology Centre, New Lister Building, Glasgow, UK
| | - Heli Harvala
- Specialist Virology Centre, Royal Infirmary of Edinburgh, UK.,Public Health Agency of Sweden (previously Swedish Institute for Communicable Disease Control), Solna, Sweden.,European Programme for Public Health Microbiology Training, European Centre for Disease Prevention and Control, Stockholm, Sweden
| | - Inka Kokki
- Specialist Virology Centre, Royal Infirmary of Edinburgh, UK
| | - Peter Simmonds
- University of Edinburgh, Roslin Institute, Easter Bush, Edinburgh EH25 9RG, UK
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Mystery of hepatitis e virus: recent advances in its diagnosis and management. Int J Hepatol 2015; 2015:872431. [PMID: 25692043 PMCID: PMC4322671 DOI: 10.1155/2015/872431] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/28/2014] [Accepted: 12/27/2014] [Indexed: 02/06/2023] Open
Abstract
Mysterious aspects of the long presumed to be well-known hepatitis E virus (HEV) have recently surfaced that distinguish it from other hepatotropic viruses. It is a cause of chronic hepatitis in immunosuppressed patients. It has human to human transmission through blood and mantains high seroprevalence in blood donors. HEV has also been found to occur more frequently in the West in those without a history of travel to endemic countries. It has varied extrahepatic manifestations and has multiple non-human reservoirs including pigs and rats. Considering these recent discoveries, it appears odd that HEV is not sought more frequently when working up acute and chronic hepatitis patients. The disease is particularly severe among pregnant women and has a high attack rate in young adults. What adds to its ambiguity is the absence of a well-established diagnostic criteria for its detection and that there is no specific antiviral drug for hepatitis E, except for isolated cases where ribavirin or pegylated interferon alpha has been used with occasional success. This review paper discusses the recent advances in the knowledge of the virus itself, its epidemiology, diagnostic approach and prevention, and the treatment options available.
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