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Elois MA, Pavi CP, Jempierre YFSH, Pilati GVT, Zanchetta L, Grisard HBDS, García N, Rodríguez-Lázaro D, Fongaro G. Trends and Challenges in the Detection and Environmental Surveillance of the Hepatitis E Virus. Microorganisms 2025; 13:998. [PMID: 40431171 PMCID: PMC12114463 DOI: 10.3390/microorganisms13050998] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2025] [Revised: 04/22/2025] [Accepted: 04/24/2025] [Indexed: 05/29/2025] Open
Abstract
The Hepatitis E virus (HEV) is responsible for causing Hepatitis E, a zoonotic disease that has emerged as a significant global health concern, accounting for about 20 million infections and 70,000 deaths annually. Although it is often recognized as a disease that is acute in low-income countries, HEV has also been recognized as a zoonotic disease in high-income countries. The zoonotic transmission requires flexible approaches to effectively monitor the virus, vectors, and reservoirs. However, the environmental monitoring of HEV presents additional challenges due to limitations in current detection methods, making it difficult to accurately assess the global prevalence of the virus. These challenges hinder efforts to fully understand the scope of the disease and to implement effective control measures. This review will explore these and other critical concerns, addressing gaps in HEV research and highlighting the need for improved strategies in the monitoring, prevention, and management of Hepatitis E using a One Health approach.
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Affiliation(s)
- Mariana Alves Elois
- Laboratory of Applied Virology, Department of Microbiology, Immunology and Parasitology, Federal University of Santa Catarina, Florianópolis 88040-900, Brazil; (M.A.E.); (C.P.P.); (Y.F.S.H.J.); (G.V.T.P.); (L.Z.); (H.B.d.S.G.); (G.F.)
- Microbiology Division, Faculty of Sciences, University of Burgos, 09001 Burgos, Spain
- Research Centre for Emerging Pathogens and Global Health, University of Burgos, 09001 Burgos, Spain
| | - Catielen Paula Pavi
- Laboratory of Applied Virology, Department of Microbiology, Immunology and Parasitology, Federal University of Santa Catarina, Florianópolis 88040-900, Brazil; (M.A.E.); (C.P.P.); (Y.F.S.H.J.); (G.V.T.P.); (L.Z.); (H.B.d.S.G.); (G.F.)
| | - Yasmin Ferreira Souza Hoffmann Jempierre
- Laboratory of Applied Virology, Department of Microbiology, Immunology and Parasitology, Federal University of Santa Catarina, Florianópolis 88040-900, Brazil; (M.A.E.); (C.P.P.); (Y.F.S.H.J.); (G.V.T.P.); (L.Z.); (H.B.d.S.G.); (G.F.)
| | - Giulia Von Tönnemann Pilati
- Laboratory of Applied Virology, Department of Microbiology, Immunology and Parasitology, Federal University of Santa Catarina, Florianópolis 88040-900, Brazil; (M.A.E.); (C.P.P.); (Y.F.S.H.J.); (G.V.T.P.); (L.Z.); (H.B.d.S.G.); (G.F.)
| | - Lucas Zanchetta
- Laboratory of Applied Virology, Department of Microbiology, Immunology and Parasitology, Federal University of Santa Catarina, Florianópolis 88040-900, Brazil; (M.A.E.); (C.P.P.); (Y.F.S.H.J.); (G.V.T.P.); (L.Z.); (H.B.d.S.G.); (G.F.)
| | - Henrique Borges da Silva Grisard
- Laboratory of Applied Virology, Department of Microbiology, Immunology and Parasitology, Federal University of Santa Catarina, Florianópolis 88040-900, Brazil; (M.A.E.); (C.P.P.); (Y.F.S.H.J.); (G.V.T.P.); (L.Z.); (H.B.d.S.G.); (G.F.)
| | - Nerea García
- Department of Animal Health, Complutense University of Madrid, 28040 Madrid, Spain;
- VISAVET Health Surveillance Centre, Complutense University of Madrid, 28040 Madrid, Spain
| | - David Rodríguez-Lázaro
- Microbiology Division, Faculty of Sciences, University of Burgos, 09001 Burgos, Spain
- Research Centre for Emerging Pathogens and Global Health, University of Burgos, 09001 Burgos, Spain
| | - Gislaine Fongaro
- Laboratory of Applied Virology, Department of Microbiology, Immunology and Parasitology, Federal University of Santa Catarina, Florianópolis 88040-900, Brazil; (M.A.E.); (C.P.P.); (Y.F.S.H.J.); (G.V.T.P.); (L.Z.); (H.B.d.S.G.); (G.F.)
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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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3
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Shata MTM, Hetta HF, Sharma Y, Sherman KE. Viral hepatitis in pregnancy. J Viral Hepat 2022; 29:844-861. [PMID: 35748741 PMCID: PMC9541692 DOI: 10.1111/jvh.13725] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/16/2021] [Revised: 12/17/2021] [Accepted: 06/13/2022] [Indexed: 12/09/2022]
Abstract
Viral hepatitis is caused by a heterogenous group of viral agents representing a wide range of phylogenetic groups. Many viruses can involve the liver and cause liver injury but only a subset are delineated as 'hepatitis viruses' based upon their primary site of replication and tropism for hepatocytes which make up the bulk of the liver cell population. Since their discovery, beginning with the agent that caused serum hepatitis in the 1960s, the alphabetic designations have been utilized. To date, we have five hepatitis viruses, A through E, though it is postulated that others may exist. This chapter will focus on those viruses. Note that hepatitis D is included as a subset of hepatitis B, as it cannot exist without concurrent hepatitis B infection. Pregnancy has the potential to affect all aspects of these viral agents due to the unique immunologic and physiologic changes that occur during and after the gestational period. In this review, we will discuss the most common viral hepatitis and their effects during pregnancy.
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Affiliation(s)
- Mohamed Tarek M. Shata
- Division of Digestive Disease, Department of Internal MedicineUniversity of CincinnatiCincinnatiOhioUSA
| | - Helal F. Hetta
- Division of Digestive Disease, Department of Internal MedicineUniversity of CincinnatiCincinnatiOhioUSA,Department of Medical Microbiology and Immunology, Faculty of MedicineAssiut UniversityAssiutEgypt
| | - Yeshika Sharma
- Division of Digestive Disease, Department of Internal MedicineUniversity of CincinnatiCincinnatiOhioUSA
| | - Kenneth E. Sherman
- Division of Digestive Disease, Department of Internal MedicineUniversity of CincinnatiCincinnatiOhioUSA
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4
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Boukhrissa H, Mechakra S, Mahnane A, Boussouf N, Gasmi A, Lacheheb A. Seroprevalence of hepatitis E virus among blood donors in eastern Algeria. Trop Doct 2022; 52:479-483. [PMID: 35791644 DOI: 10.1177/00494755221112212] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
Hepatitis E virus (HEV) is recognized worldwide as the leading cause of orofecal-transmitted hepatitis. However, blood transmission has been increasingly implicated in recent years raising health concerns. In Algeria, updated prevalence data are lacking. We aimed to determine the prevalence of anti-HEV antibodies in the sera of volunteer blood donors from the Setif region in eastern Algeria. A total of 434 Samples were analyzed for anti-HEV IgG and IgM antibodies using an enzyme-linked immunosorbent assay (Wantai). Logistic regression modelling was used to identify associated risk factors. The IgG seroprevalence rate was 17.05%. Seven sera (0.16%) were weakly positive for IgM. No HEV RNA was detected. The IgG prevalence was significantly correlated with increasing age (p < 1p.1000). Our data demonstrate a relatively high prevalence of anti-HEV IgG, indicating a possible risk of HEV blood transmission which requires vireamic seroprevalence studies to assess the real risk.
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Affiliation(s)
- Houda Boukhrissa
- Faculty of Medicine, Department of Infectious Diseases, 277693University Ferhat Abbas Setif 1, Algeria
| | - Saleh Mechakra
- Faculty of Medicine, Department of Infectious Diseases, 277693University Ferhat Abbas Setif 1, Algeria
| | - Abbes Mahnane
- Faculty of Medicine, Department of Infectious Diseases, 277693University Ferhat Abbas Setif 1, Algeria
| | - Nadir Boussouf
- Faculty of Medicine, Department of epidemiology and preventive medicine, 389767University of Constantine 3, Algeria
| | - Abdelkader Gasmi
- Faculty of Medicine, Department of Infectious Diseases, 277693University Ferhat Abbas Setif 1, Algeria
| | - Abdelmadjid Lacheheb
- Faculty of Medicine, Department of Infectious Diseases, 277693University Ferhat Abbas Setif 1, Algeria
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5
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Raji YE, Toung OP, Taib NM, Sekawi ZB. Hepatitis E Virus: An emerging enigmatic and underestimated pathogen. Saudi J Biol Sci 2022; 29:499-512. [PMID: 35002446 PMCID: PMC8716866 DOI: 10.1016/j.sjbs.2021.09.003] [Citation(s) in RCA: 39] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2020] [Revised: 08/31/2021] [Accepted: 09/05/2021] [Indexed: 02/07/2023] Open
Abstract
Hepatitis E virus (HEV) is an RNA virus causing hepatitis E disease. The virus is of one serotype but has diverse genotypes infecting both humans and animals. Based on evidence from seroprevalence studies, about 2 billion people are estimated to have been infected with HEV globally. HEV, therefore, poses a significant public health and economic challenge worldwide. HEV was discovered in the 1980s and was traced back to the 1955 - 1956 outbreak of hepatitis that occurred in India. Subsequently, several HEV epidemics involving thousands of individuals have occurred nearly annually in different countries in Asia and Africa. Initially, the virus was thought to be only enterically transmitted, and endemic in developing countries. Due to the environmental hygiene and sanitation challenges in those parts of the world. However, recent studies have suggested otherwise with the report of autochthonous cases in industrialised countries with no history of travel to the so-called endemic countries. Thus, suggesting that HEV has a global distribution with endemicity in both developing and industrialised nations. Studies have also revealed that HEV has multiple risk factors, and modes of transmission as well as zoonotic potentials. Additionally, recent findings have shown that HEV leads to severe disease, particularly among pregnant women. In contrast to the previous narration of a strictly mild and self-limiting infection. Studies have likewise demonstrated chronic HEV infection among immunocompromised persons. Consequent to these recent discoveries, this pathogen is considered a re - emerging virus, particularly in the developed nations. However, despite the growing public health challenges of this pathogen, the burden is still underestimated. The underestimation is often attributed to poor awareness among clinicians and a lack of routine checks for the disease in the hospitals. Thus, leading to misdiagnosis and underdiagnosis. Hence, this review provides a concise overview of epidemiology, diagnosis, and prevention of hepatitis E.
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Affiliation(s)
- Yakubu Egigogo Raji
- Department of Medical Microbiology and Parasitology, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia 1, Malaysia
- Faculty of Natural and Applied Sciences Ibrahim Badamasi Babangida University, Lapai, Nigeria
| | - Ooi Peck Toung
- Department of Veterinary Clinical Studies Faculty of Veterinary Medicine, Universiti Putra Malaysia 2, Malaysia
| | - Niazlin Mohd Taib
- Department of Medical Microbiology and Parasitology, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia 1, Malaysia
| | - Zamberi Bin Sekawi
- Department of Medical Microbiology and Parasitology, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia 1, Malaysia
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Lienhard J, Vonlanthen-Specker I, Sidler X, Bachofen C. Screening of Swiss Pig Herds for Hepatitis E Virus: A Pilot Study. Animals (Basel) 2021; 11:3050. [PMID: 34827782 PMCID: PMC8614339 DOI: 10.3390/ani11113050] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2021] [Revised: 10/20/2021] [Accepted: 10/21/2021] [Indexed: 12/14/2022] Open
Abstract
Hepatitis E virus (HEV) is an important cause of acute hepatitis in humans worldwide. In industrialised countries, most infections are caused by the zoonotic genotype 3. The main reservoir was found in pigs, with fattening pigs as the main shedders. The aim of this study was to establish a screening tool to detect HEV in pig farms. HEV-positive samples were sequenced using Sanger sequencing. First, different sample materials, including floor swabs, slurry, dust swabs and faeces were tested for HEV. Floor swabs turned out to give the best results and, in the form of sock swabs, were used for the screening of Swiss pig herds. A total of 138 pig farms were tested, with a focus on fattening pigs. Overall, 81 farms (58.8%) were HEV positive. Most sequences belonged to subtype 3h, in which they formed a specific cluster (Swiss cluster). In addition, subtype 3l and two unassigned sequences were detected. As a conclusion, sock swabs were found to be a helpful tool to screen pig herds for HEV and establish a sequence collection that may enable molecular epidemiology and support outbreak investigation and prevention.
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Affiliation(s)
- Julia Lienhard
- Institute of Virology, Vetsuisse Faculty, University of Zurich, 8057 Zurich, Switzerland; (J.L.); (I.V.-S.)
| | | | - Xaver Sidler
- Division of Swine Medicine, Department of Farm Animals, Vetsuisse Faculty, University of Zurich, 8057 Zurich, Switzerland;
| | - Claudia Bachofen
- Institute of Virology, Vetsuisse Faculty, University of Zurich, 8057 Zurich, Switzerland; (J.L.); (I.V.-S.)
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Mei X, Dai F, Zou J, Zhang H, Yuan Z, Qian Z, Yi Z. Quasispecies dynamics of a hepatitis E virus 4 from the feces and liver biopsy of an acute hepatitis E patient during virus clearance. J Med Virol 2020; 92:3556-3562. [PMID: 32129506 DOI: 10.1002/jmv.25746] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2019] [Accepted: 03/01/2020] [Indexed: 12/25/2022]
Abstract
The presence of a quasispecies in hepatitis E virus (HEV) infection has been documented, however, the implications of a quasispecies in HEV-host interaction are poorly understood. Here, we analyzed the whole genome sequences of a HEV 4d from the feces and liver biopsy of a patient during the icteric and convalescent phases in an acute hepatitis E infection. Viral RNAs were extracted, reversely transcribed and seven fragments encompassing the entire viral genome were amplified and cloned. By sequencing multiple colonies of each cloned viral genome amplicon with Sanger sequencing, we verified the existence of the HEV quasispecies or intra-host genetic variations within the fecal and liver biopsy samples. There were broader genetic variations in the HEV ORF1 region including the PCP, HPX, and RdRp regions during the convalescent phase whereas more genetic variations in the ORF2 P domain during the icteric phase. The quasispecies dynamics might reflect host immune pressure during viral clearance.
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Affiliation(s)
- Xue Mei
- Shanghai Public Health Clinical Center, Fudan University, Shanghai, China
| | - Fahui Dai
- Shanghai Public Health Clinical Center, Fudan University, Shanghai, China
| | - Jingyi Zou
- Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), School of Basic Medicine, Shanghai Medical College, Fudan University, Shanghai, China
| | - Huiying Zhang
- Shanghai Public Health Clinical Center, Fudan University, Shanghai, China
| | - Zhenghong Yuan
- Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), School of Basic Medicine, Shanghai Medical College, Fudan University, Shanghai, China
| | - Zhiping Qian
- Shanghai Public Health Clinical Center, Fudan University, Shanghai, China
| | - Zhigang Yi
- Shanghai Public Health Clinical Center, Fudan University, Shanghai, China
- Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), School of Basic Medicine, Shanghai Medical College, Fudan University, Shanghai, China
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Ledesma J, Williams D, Stanford FA, Hewitt PE, Zuckerman M, Bansal S, Dhawan A, Mbisa JL, Tedder R, Ijaz S. Resolution by deep sequencing of a dual hepatitis E virus infection transmitted via blood components. J Gen Virol 2020; 100:1491-1500. [PMID: 31592753 DOI: 10.1099/jgv.0.001302] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
Hepatitis E virus (HEV) is a zoonotic infection, with consumption of processed pork products thought to be the major route of transmission in England. The clinical features of HEV infection range from asymptomatic infection to mild hepatitis to fulminant liver failure. Persistent, chronic hepatitis is increasingly recognized in immunocompromised patients. Infection via HEV-containing blood components and organs has been reported and measures to reduce this transmission risk were introduced into the blood service in England in 2016. We report here the sequence and phylogenetic findings from investigations into a transmission event from an HEV-infected donor to two recipients. Phylogenetic analysis of HEV genome sequence fragments obtained by Sanger sequencing showed that, whilst most of the sequences from both recipients' samples grouped with the sequence from the blood donor sample, the relationship of five sequences from recipient 2 were unresolved. Analysis of Illumina short-read deep sequence data demonstrated the presence of two divergent viral populations in the donor's sample that were also present in samples from both recipients. A clear phylogenetic relationship was established, indicating a probable transmission of both populations from the donor to each of the immunocompromised recipients. This study demonstrates the value of the application of new sequencing technologies combined with bioinformatic data analysis when Sanger sequencing is not able to clarify a proper phylogenetic relationship in the investigation of transmission events.
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Affiliation(s)
- Juan Ledesma
- National Institute for Health Research Health Protection Research Unit (NIHR HPRU) in Blood Borne and Sexually Transmitted Infections, London, UK.,Antiviral Unit, Virus Reference Department, National Infection Service, Public Health England, London, UK
| | - David Williams
- Bioinformatics, Virus Reference Department, National Infection Service, Public Health England, London, UK
| | - Felicia Adelina Stanford
- Blood Borne Virus Unit, Virus Reference Department, National Infection Service, Public Health England, London, UK
| | | | - Mark Zuckerman
- South London Specialist Virology Centre, King's College Hospital NHS Foundation Trust, London, UK
| | - Sanjay Bansal
- Paediatric Liver, GI and Nutrition Centre and Mowat Labs, King's College Hospital, London, UK
| | - Anil Dhawan
- Paediatric Liver, GI and Nutrition Centre and Mowat Labs, King's College Hospital, London, UK
| | - Jean Lutamyo Mbisa
- National Institute for Health Research Health Protection Research Unit (NIHR HPRU) in Blood Borne and Sexually Transmitted Infections, London, UK.,Antiviral Unit, Virus Reference Department, National Infection Service, Public Health England, London, UK
| | - Richard Tedder
- Blood Borne Virus Unit, Virus Reference Department, National Infection Service, Public Health England, London, UK
| | - Samreen Ijaz
- Blood Borne Virus Unit, Virus Reference Department, National Infection Service, Public Health England, London, UK.,National Institute for Health Research Health Protection Research Unit (NIHR HPRU) in Blood Borne and Sexually Transmitted Infections, London, UK
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Hepatitis E Virus Shows More Genomic Alterations in Cell Culture than In Vivo. Pathogens 2019; 8:pathogens8040255. [PMID: 31766624 PMCID: PMC6963849 DOI: 10.3390/pathogens8040255] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2019] [Revised: 11/12/2019] [Accepted: 11/18/2019] [Indexed: 12/16/2022] Open
Abstract
Hepatitis E Virus (HEV) mutations following ribavirin treatment have been associated with treatment non-response and viral persistence, but spontaneous occurring genomic variations have been less well characterized. We here set out to study the HEV genome composition in 2 patient sample types and 2 infection models. Near full HEV genome Sanger sequences of serum- and feces-derived HEV from two chronic HEV genotype 3 (gt3) patients were obtained. In addition, viruses were sequenced after in vitro or in vivo expansion on A549 cells or a humanized mouse model, respectively. We show that HEV acquired 19 nucleotide mutations, of which 7 nonsynonymous amino acids changes located in Open Reading Frame 1 (ORF1), ORF2, and ORF3 coding regions, after prolonged in vitro culture. In vivo passage resulted in selection of 8 nucleotide mutations with 2 altered amino acids in the X domain and Poly-proline region of ORF1. Intra-patient comparison of feces- and serum-derived HEV gt3 of two patients showed 7 and 2 nucleotide mutations with 2 and 0 amino acid changes, respectively. Overall, the number of genomic alterations was up to 1.25× per 1000 nucleotides or amino acids in in vivo samples, and up to 2.84× after in vitro expansion of the same clinical HEV strain. In vitro replication of a clinical HEV strain is therefore associated with more mutations, compared to the minor HEV genomic alterations seen after passage of the same strain in an immune deficient humanized mouse; as well as in feces and blood of 2 immunosuppressed chronically infected HEV patients. These data suggest that HEV infected humanized mice more closely reflect the HEV biology seen in solid organ transplant recipients.
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10
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Novel Synthesis and Phenotypic Analysis of Mutant Clouds for Hepatitis E Virus Genotype 1. J Virol 2018; 92:JVI.01932-17. [PMID: 29167341 DOI: 10.1128/jvi.01932-17] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2017] [Accepted: 11/07/2017] [Indexed: 12/14/2022] Open
Abstract
Many RNA viruses exist as an ensemble of genetically diverse, replicating populations known as a mutant cloud. The genetic diversity (cloud size) and composition of this mutant cloud may influence several important phenotypic features of the virus, including its replication capacity. We applied a straightforward, bacterium-free approach using error-prone PCR coupled with reverse genetics to generate infectious mutant RNA clouds with various levels of genetic diversity from a genotype 1 strain of hepatitis E virus (HEV). Cloning and sequencing of a genomic fragment encompassing 70% of open reading frame 1 (ORF1) or of the full genome from variants in the resultant clouds showed the occurrence of nucleotide mutations at a frequency on the order of 10-3 per nucleotide copied and the existence of marked genetic diversity, with a high normalized Shannon entropy value. The mutant clouds showed transient replication in cell culture, while wild-type HEV did not. Cross-sectional data from these cell cultures supported the existence of differential effects of clouds of various sizes and compositions on phenotypic characteristics, such as the replication level of (+)-RNA progeny, the amounts of double-stranded RNA (a surrogate for the rate of viral replication) and ORF1 protein, and the expression of interferon-stimulated genes. Since mutant cloud size and composition influenced the viral phenotypic properties, a better understanding of this relationship may help to provide further insights into virus evolution and prediction of emerging viral diseases.IMPORTANCE Several biological or practical limitations currently prevent the study of phenotypic behavior of a mutant cloud in vitro We developed a simple and rapid method for synthesizing mutant clouds of hepatitis E virus (HEV), a single-stranded (+)-RNA [ss(+) RNA] virus, with various and controllable levels of genetic diversity, which could then be used in a cell culture system to study the effects of cloud size and composition on viral phenotype. In a cross-sectional analysis, we demonstrated that a particular mutant cloud which had an extremely high genetic diversity had a replication rate exceeding that of wild-type HEV. This method should thus provide a useful model for understanding the phenotypic behavior of ss(+) RNA viruses.
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11
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Hakim MS, Ikram A, Zhou J, Wang W, Peppelenbosch MP, Pan Q. Immunity against hepatitis E virus infection: Implications for therapy and vaccine development. Rev Med Virol 2017; 28. [PMID: 29272060 DOI: 10.1002/rmv.1964] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2017] [Revised: 11/10/2017] [Accepted: 11/14/2017] [Indexed: 12/20/2022]
Abstract
Hepatitis E virus (HEV) is the leading cause of acute viral hepatitis worldwide and an emerging cause of chronic infection in immunocompromised patients. As with viral infections in general, immune responses are critical to determine the outcome of HEV infection. Accumulating studies in cell culture, animal models and patients have improved our understanding of HEV immunopathogenesis and informed the development of new antiviral therapies and effective vaccines. In this review, we discuss the recent progress on innate and adaptive immunity in HEV infection, and the implications for the devolopment of effective vaccines and immune-based therapies.
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Affiliation(s)
- Mohamad S Hakim
- Department of Gastroenterology and Hepatology, Erasmus MC-University Medical Center and Postgraduate School Molecular Medicine, Rotterdam, The Netherlands.,Department of Microbiology, Faculty of Medicine, Universitas Gadjah Mada, Yogyakarta, Indonesia
| | - Aqsa Ikram
- Department of Gastroenterology and Hepatology, Erasmus MC-University Medical Center and Postgraduate School Molecular Medicine, Rotterdam, The Netherlands.,Atta-Ur-Rahman School of Applied Biosciences, National University of Science and Technology, Islamabad, Pakistan
| | - Jianhua Zhou
- Department of Gastroenterology and Hepatology, Erasmus MC-University Medical Center and Postgraduate School Molecular Medicine, Rotterdam, The Netherlands.,State Key Laboratory of Veterinary Etiological Biology, National Foot-and-Mouth Disease Reference Laboratory, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, Gansu, PR China
| | - Wenshi Wang
- Department of Gastroenterology and Hepatology, Erasmus MC-University Medical Center and Postgraduate School Molecular Medicine, Rotterdam, The Netherlands
| | - Maikel P Peppelenbosch
- Department of Gastroenterology and Hepatology, Erasmus MC-University Medical Center and Postgraduate School Molecular Medicine, Rotterdam, The Netherlands
| | - Qiuwei Pan
- Department of Gastroenterology and Hepatology, Erasmus MC-University Medical Center and Postgraduate School Molecular Medicine, Rotterdam, The Netherlands
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12
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Pelosi E, Clarke I. Hepatitis E: a complex and global disease. EMERGING HEALTH THREATS JOURNAL 2017. [DOI: 10.3402/ehtj.v1i0.7069] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Affiliation(s)
- E Pelosi
- Department of Microbiology and Virology, Health Protection Agency, Southeast Regional Laboratory, Southampton General Hospital, Southampton, UK; and
| | - I Clarke
- Department of Molecular Microbiology, Southampton Medical School, Southampton General Hospital, Southampton, UK
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Hakim MS, Wang W, Bramer WM, Geng J, Huang F, de Man RA, Peppelenbosch MP, Pan Q. The global burden of hepatitis E outbreaks: a systematic review. Liver Int 2017; 37:19-31. [PMID: 27542764 DOI: 10.1111/liv.13237] [Citation(s) in RCA: 85] [Impact Index Per Article: 10.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/23/2016] [Accepted: 08/15/2016] [Indexed: 12/12/2022]
Abstract
Hepatitis E virus (HEV) is responsible for repeated water-borne outbreaks since the past century, representing an emerging issue in public health. However, the global burden of HEV outbreak has not been comprehensively described. We performed a systematic review of confirmed HEV outbreaks based on published literatures. HEV outbreaks have mainly been reported from Asian and African countries, and only a few from European and American countries. India represents a country with the highest number of reported HEV outbreaks. HEV genotypes 1 and 2 were responsible for most of the large outbreaks in developing countries. During the outbreaks in developing countries, a significantly higher case fatality rate was observed in pregnant women. In fact, outbreaks have occurred both in open and closed populations. The control measures mainly depend upon improvement of sanitation and hygiene. This study highlights that HEV outbreak is not new, yet it is a continuous global health problem.
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Affiliation(s)
- Mohamad S Hakim
- Department of Gastroenterology and Hepatology, Erasmus MC-University Medical Center Rotterdam, Rotterdam, the Netherlands.,Department of Microbiology, Faculty of Medicine, Gadjah Mada University, Yogyakarta, Indonesia
| | - Wenshi Wang
- Department of Gastroenterology and Hepatology, Erasmus MC-University Medical Center Rotterdam, Rotterdam, the Netherlands
| | - Wichor M Bramer
- Medical Library, Erasmus MC-University Medical Center Rotterdam, Rotterdam, the Netherlands
| | - Jiawei Geng
- Department of Infectious Diseases, The First People's Hospital of Yunnan Province, Kunming, China
| | - Fen Huang
- Medical Faculty, Kunming University of Science and Technology, Kunming, China
| | - Robert A de Man
- Department of Gastroenterology and Hepatology, Erasmus MC-University Medical Center Rotterdam, Rotterdam, the Netherlands
| | - Maikel P Peppelenbosch
- Department of Gastroenterology and Hepatology, Erasmus MC-University Medical Center Rotterdam, Rotterdam, the Netherlands
| | - Qiuwei Pan
- Department of Gastroenterology and Hepatology, Erasmus MC-University Medical Center Rotterdam, Rotterdam, the Netherlands
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Todt D, Walter S, Brown RJP, Steinmann E. Mutagenic Effects of Ribavirin on Hepatitis E Virus-Viral Extinction versus Selection of Fitness-Enhancing Mutations. Viruses 2016; 8:E283. [PMID: 27754363 PMCID: PMC5086615 DOI: 10.3390/v8100283] [Citation(s) in RCA: 38] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2016] [Revised: 09/30/2016] [Accepted: 10/06/2016] [Indexed: 12/11/2022] Open
Abstract
Hepatitis E virus (HEV), an important agent of viral hepatitis worldwide, can cause severe courses of infection in pregnant women and immunosuppressed patients. To date, HEV infections can only be treated with ribavirin (RBV). Major drawbacks of this therapy are that RBV is not approved for administration to pregnant women and that the virus can acquire mutations, which render the intra-host population less sensitive or even resistant to RBV. One of the proposed modes of action of RBV is a direct mutagenic effect on viral genomes, inducing mismatches and subsequent nucleotide substitutions. These transition events can drive the already error-prone viral replication beyond an error threshold, causing viral population extinction. In contrast, the expanded heterogeneous viral population can facilitate selection of mutant viruses with enhanced replication fitness. Emergence of these mutant viruses can lead to therapeutic failure. Consequently, the onset of RBV treatment in chronically HEV-infected individuals can result in two divergent outcomes: viral extinction versus selection of fitness-enhanced viruses. Following an overview of RNA viruses treated with RBV in clinics and a summary of the different antiviral modes of action of this drug, we focus on the mutagenic effect of RBV on HEV intrahost populations, and how HEV is able to overcome lethal mutagenesis.
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Affiliation(s)
- Daniel Todt
- Institute of 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, 30625 Hannover, Germany.
| | - Stephanie Walter
- Institute of 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, 30625 Hannover, Germany.
| | - Richard J P Brown
- Institute of 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, 30625 Hannover, Germany.
| | - Eike Steinmann
- Institute of 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, 30625 Hannover, Germany.
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Behloul N, Zhang M, Meng J. Binding Preference of Anti-HEV Antibodies in Sera Collected in Algeria for Antigens Derived From HEV Genotype 1. HEPATITIS MONTHLY 2016; 16:e35312. [PMID: 27795723 PMCID: PMC5070561 DOI: 10.5812/hepatmon.35312] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/22/2015] [Revised: 02/26/2016] [Accepted: 05/10/2016] [Indexed: 12/11/2022]
Abstract
BACKGROUND Two hepatitis E virus (HEV) outbreaks occurred in Algeria (1979 - 1980 and 1987 - 1988). However, to date, no study on the prevalence of anti-HEV antibodies has been conducted in Algeria, and the genotype of the circulating strains remains unclear. OBJECTIVES This study was conducted to investigate the presence of anti- HEV antibodies among outpatients and blood donors in three different hospitals in Northern Algeria and to determine the genotype of the circulating strains through the characterization of the immunoreactivity of anti-HEV antibodies. METHODS A total of 590 blood samples (379 from blood donors and 211 from outpatients) were collected in three health facilities in Northern Algeria and assessed for anti-HEV antibodies using an in-house double-antigen sandwich immunoassay. HEV open reading frame 2 recombinant proteins p166 (aa 452 - 617) generated from the four HEV genotypes were used as antigens. The genotype of the strains circulating in Algeria was predicted by an indirect ELISA by assessing the anti-HEV antibodies in serially diluted positive sera using the different p166 proteins. RESULTS Anti-HEV antibodies were detected in 20.17% of the samples. A significant correlation was found between the age of the subjects and the presence of anti-HEV antibodies (P < 0.001). Among blood donors, 83 (21.9%) were diagnosed positive for anti-HEV antibodies with two cases weakly positive for anti-HEV IgM antibodies. Moreover, 9.9% of the subjects aged less than 25 years old (born after the last HEV outbreak) were positive for anti-HEV antibodies. The indirect ELISA revealed that the anti-HEV antibodies within the positive sera reacted more strongly against the p166 antigens generated from genotype 1. CONCLUSIONS The present findings reveal a relatively high presence of anti-HEV IgGs and clearly indicate that HEV infection is still present in Northern Algeria. Further, the prediction of HEV genotype using different antigens generated from the different HEV genotypes shows that the causative strains are more likely to be of genotype 1.
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Affiliation(s)
- Nouredine Behloul
- Department of Microbiology and Immunology, Southeast University School of Medicine, Nanjing, China
| | - Min Zhang
- Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China
| | - Jihong Meng
- Department of Microbiology and Immunology, Southeast University School of Medicine, Nanjing, China
- Corresponding Author: Jihong Meng, Department of Microbiology and Immunology, Southeast University School of Medicine, Nanjing, China. Tel/Fax: +86-2583272386, E-mail:
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Motoya T, Nagata N, Komori H, Doi I, Kurosawa M, Keta T, Sasaki N, Ishii K. The high prevalence of hepatitis E virus infection in wild boars in Ibaraki Prefecture, Japan. J Vet Med Sci 2015; 77:1705-9. [PMID: 26234737 PMCID: PMC4710736 DOI: 10.1292/jvms.15-0173] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023] Open
Abstract
Hepatitis E virus (HEV) is known as a causative agent of zoonosis and food poisoning.
Pigs and some species of wild animals, including wild boar, are known to be a reservoir of
HEV. In this study, we investigated the situation regarding HEV infection in wild boars in
Ibaraki Prefecture, Japan. Serum, liver and feces samples from 68 animals were collected,
and the presence or absence of HEV genomic RNA and HEV antibodies were analyzed. The viral
genome was detected in samples from 7 (10.3%) animals, with all HEVs classified as
genotype 3, subtype 3b. HEV antibodies were detected in samples from 28 (41%) animals.
This report demonstrates for the first time the high prevalence of HEV infection in wild
boars in Ibaraki Prefecture.
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Affiliation(s)
- Takumi Motoya
- Ibaraki Prefectural Institute of Public Health, 993-2 Kasahara-cho, Mito, Ibaraki 310-0852, Japan
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Černi S, Prpić J, Jemeršić L, Škorić D. The application of single strand conformation polymorphism (SSCP) analysis in determining Hepatitis E virus intra-host diversity. J Virol Methods 2015; 221:46-50. [PMID: 25920567 DOI: 10.1016/j.jviromet.2015.04.020] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2014] [Revised: 04/14/2015] [Accepted: 04/16/2015] [Indexed: 01/23/2023]
Abstract
Genetic heterogeneity of RNA populations influences virus pathogenesis, epidemiology and evolution. Therefore, accurate information regarding virus genetic structure is highly important for both diagnostic and scientific purposes. For the Hepatitis E virus (HEV), the causal agent of hepatitis in humans, the intra-host population structure has been poorly investigated, mainly using the less sensitive RFLP-based approach. The objective of this study was to assess the suitability and the accuracy of single strand conformation polymorphism (SSCP) analysis, a well-established tool in genetic variation research, for the characterization of HEV quasispecies. The analysis was conducted on 50 clones of five swine isolates and 30 clones of three human HEV isolates. To identify and quantify the sequence variants present in each HEV isolate, 348bp long fragments of the amplified conserved ORF2 region were separated by cloning. Ten clones per isolate were subjected to SSCP and sequenced in a parallel experiment. The results show a high correlation of SSCP haplotype profiling with the sequencing results, confirming the sensitivity and reliability of this simple, rapid and low cost approach in the characterization of HEV quasispecies.
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Affiliation(s)
- S Černi
- University of Zagreb, Faculty of Science, Department of Biology, Marulićev trg 9A, Zagreb, Croatia
| | - J Prpić
- Croatian Veterinary Institute, Department of Virology, Savska cesta 143, Zagreb, Croatia
| | - L Jemeršić
- Croatian Veterinary Institute, Department of Virology, Savska cesta 143, Zagreb, Croatia
| | - D Škorić
- University of Zagreb, Faculty of Science, Department of Biology, Marulićev trg 9A, Zagreb, Croatia.
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Characterization of the polyproline region of the hepatitis E virus in immunocompromised patients. J Virol 2014; 88:12017-25. [PMID: 25100839 DOI: 10.1128/jvi.01625-14] [Citation(s) in RCA: 53] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
Little is known about virus adaptation in immunocompromised patients with chronic genotype 3 hepatitis E virus (HEV3) infections. Virus-host recombinant strains have been isolated recently from chronically infected patients. The nature and incidence of such recombinant events occurring during infections of solid-organ transplant (SOT) recipients are essentially unknown. The polyproline region (PPR) of strains isolated from SOT patients was sequenced during the acute-infection phase (n = 59) and during follow-up of patients whose infections became chronic (n = 27). These 27 HEV strains included 3 (11%) that showed recombinant events 12, 34, 48, or 88 months after infection. In one strain, parts of the PPR and the RNA-dependent RNA polymerase were concomitantly inserted. In the second, a fragment of a human tyrosine aminotransferase (TAT) gene was inserted first, followed by a fragment of PPR. A fragment of the human inter-α-trypsin inhibitor (ITI) gene was inserted in the third. All the inserted sequences were rich in aliphatic and basic amino acids. In vitro growth experiments suggest that the ITI insertion promoted more vigorous virus growth. In silico studies showed that the inserted sequences could provide potential acetylation, ubiquitination, and phosphorylation sites. We found that recombinant events had occurred in the HEV PPR in approximately 11% of the strains isolated from chronically infected transplant patients followed up in Toulouse University Hospital. These inserted fragments came from the HEV genome or a human gene and could enhance virus replication. Importance: Hepatitis E virus (HEV) can cause chronic infections in immunocompromised patients, including solid-organ transplant (SOT) recipients. Two strains that had undergone recombination with human ribosomal genes were described recently. The strains with inserted sequences replicated better in vitro. Little is known about the frequency of such recombinant events or how such an insertion enhances replication. We therefore investigated 59 SOT patients infected with HEV and found 3 strains with 4 recombinant events in 27 of these patients whose infection became chronic. The 4 inserted sequences were of different origins (human gene or HEV genome), but all were enriched in aliphatic and basic amino acids and provided potential regulation sites. Our data indicate that recombinant events occur in approximately 11% of strains isolated from chronically infected patients. The structures of the inserted sequences provide new clues as to how the inserted sequences could foster virus replication.
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Yang D, Jiang M, Jin M, Qiu ZG, Shen ZQ, Cui WH, Wang DN, Gong LF, Li B, Wang XW, Li JW. Seroprevalence and evolutionary dynamics of genotype 4 hepatitis E virus in Shandong Province, China. World J Gastroenterol 2014; 20:7955-7963. [PMID: 24976732 PMCID: PMC4069323 DOI: 10.3748/wjg.v20.i24.7955] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/16/2014] [Revised: 03/25/2014] [Accepted: 04/09/2014] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the seroprevalence and evolutionary dynamics of hepatitis E virus (HEV) and assess the ancestor of HEVs in China’s Shandong Province.
METHODS: A total of 2028 serum, 60 fecal and 82 bile samples were collected from the general human population, patients and swine, respectively. This seroepidemiological study was conducted using an immunnosorbent assay and HEV RNA was detected by the reverse transcription-nested polymerase chain reaction (RT-nPCR) method. Complete genome sequences of the prevalent strains (CH-YT-HEV01, CH-YT-HEV02 and CH-YT-sHEV01) were determined, and the sequences were analyzed phylogenetically. In addition, the evolutionary dynamics of three HEV isolates were determined using the framework of coalescent analysis in the program package BEAST, and the time of the most recent common ancestors (TMRCAs) of China-indigenous genotype 4 HEV isolates was calculated.
RESULTS: The overall viral burden in the general human population was 0.1%, and the positive rates of anti-HEV IgG and IgM in the serum specimens were 25.1% (509/2028) and 2.3% (51/2028), respectively. In addition, IgG positivity increased with age. The phylogenetic analysis based on the full-length nucleotide sequences showed that the strain CH-YT-HEV02 was directly related to CH-YT-sHEV01 with a 94% identity, suggesting that they were involved in cross-species transmission. The isolate CH-YT-HEV01 was close to HB-3 and CHN-SD-sHEV with a bootstrap value of 100%, sharing a 96.1%-96.4% identity with each other. Surprisingly, the HB-3 strain was a representative strain prevalent in swine in Hubei, and the isolate CHN-SD-sHEV was obtained from swine in Shandong in a previous report. TMRCA for the clade of CH-YT-HEV01 and HB-3 was 2003, which was consistent with the TMRCA for the clade of CHN-SD-sHEV and HB-3, and they were both earlier than the TMRCA for the clade of CH-YT-HEV01 and CHN-SD-sHEV (2004).
CONCLUSION: The strains CH-YT-HEV01, CHN-SD-sHEV and HB-3 are involved in trans-regional transmission, and the ancestors of HEVs in Shandong come from Hubei Province.
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Lara J, Purdy MA, Khudyakov YE. Genetic host specificity of hepatitis E virus. INFECTION, GENETICS AND EVOLUTION : JOURNAL OF MOLECULAR EPIDEMIOLOGY AND EVOLUTIONARY GENETICS IN INFECTIOUS DISEASES 2014; 24:127-39. [PMID: 24667049 PMCID: PMC5745802 DOI: 10.1016/j.meegid.2014.03.011] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/20/2013] [Revised: 02/24/2014] [Accepted: 03/16/2014] [Indexed: 01/06/2023]
Abstract
Hepatitis E virus (HEV) causes epidemic and sporadic cases of hepatitis worldwide. HEV genotypes 3 (HEV3) and 4 (HEV4) infect humans and animals, with swine being the primary reservoir. The relevance of HEV genetic diversity to host adaptation is poorly understood. We employed a Bayesian network (BN) analysis of HEV3 and HEV4 to detect epistatic connectivity among protein sites and its association with the host specificity in each genotype. The data imply coevolution among ∼70% of polymorphic sites from all HEV proteins and association of numerous coevolving sites with adaptation to swine or humans. BN models for individual proteins and domains of the nonstructural polyprotein detected the host origin of HEV strains with accuracy of 74-93% and 63-87%, respectively. These findings, taken together with lack of phylogenetic association to host, suggest that the HEV host specificity is a heritable and convergent phenotypic trait achievable through variety of genetic pathways (abundance), and explain a broad host range for HEV3 and HEV4.
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Affiliation(s)
- James Lara
- Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, GA, USA.
| | - Michael A Purdy
- Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, GA, USA
| | - Yury E Khudyakov
- Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, GA, USA
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Hepatitis E: an emerging disease. INFECTION GENETICS AND EVOLUTION 2014; 22:40-59. [PMID: 24434240 DOI: 10.1016/j.meegid.2014.01.002] [Citation(s) in RCA: 89] [Impact Index Per Article: 8.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/17/2013] [Revised: 12/09/2013] [Accepted: 01/04/2014] [Indexed: 02/07/2023]
Abstract
Currently, the infection with the hepatitis E virus represents the most frequent cause for acute hepatitis and jaundice in the world. According to WHO estimations, around two billion people, representing one third of the world's population, live in endemic areas for HEV and, therefore, are at risk of infection. In developed countries, the circulation of the virus in both human and animal (swine, boar, deer) sewage has been confirmed; however, the incidence rate is low compared to that of developing countries where outbreaks of acute hepatitis transmitted via the fecal-oral route are originated, more frequently in the flooding season or after natural disasters, combined with deficient sanitary conditions. There are currently 4 known genotypes of HEV. Genotypes 1 and 2 are isolated in all human epidemic outbreaks in developing countries, while genotypes 3 and 4 are isolated not only in humans but also in animals, in both developing and industrialized countries. These data support genotypes 3 and 4 having zoonotic nature. The diagnosis of this disease is based in the detection of anti-HEV IgG and IgM in blood serum using enzyme-linked immunosorbent methods. However, the method that best confirms the diagnosis is the RT-PCR, which detects HEV RNA in blood serum and also provides the genotype. The clinical course is generally that of an acute hepatitis which in some cases may require hospitalization and that, in transplant patients or HIV infected individuals can become a chronic hepatitis. Furthermore, the virus constitutes an important risk for pregnant women. The hepatitis E can present a wide range of symptoms, from a subclinical case to chronic liver disease with extrahepatic manifestations. For this reason, the diagnostic is challenging if no differential diagnosis is included. There is no specific antiviral drug for hepatitis E, but satisfactory results have been observed in some patients treated with pegylated interferon alfa2a and/or ribavirin. This revision is an update of all the molecular, epidemiological, clinic and preventive knowledge on this emergent disease up to date.
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Mulyanto, Suparyatmo JB, Andayani IGAS, Khalid, Takahashi M, Ohnishi H, Jirintai S, Nagashima S, Nishizawa T, Okamoto H. Marked genomic heterogeneity of rat hepatitis E virus strains in Indonesia demonstrated on a full-length genome analysis. Virus Res 2013; 179:102-12. [PMID: 24231359 DOI: 10.1016/j.virusres.2013.10.029] [Citation(s) in RCA: 50] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2013] [Revised: 10/30/2013] [Accepted: 10/30/2013] [Indexed: 12/26/2022]
Abstract
Rat hepatitis E virus (HEV) strains have recently been isolated in several areas of Germany, Vietnam, the United States, Indonesia and China. However, genetic information regarding these rat HEV strains is limited. A total of 369 wild rats (Rattus rattus) captured in Central Java (Solo) and on Lombok Island, Indonesia were tested for the presence of rat HEV-specific antibodies and RNA. Overall, 137 rats (37.1%) tested positive for rat anti-HEV antibodies, while 97 (26.3%) had rat HEV RNA detectable on reverse transcription-PCR with primers targeting the ORF1-ORF2 junctional region. The 97 HEV strains recovered from these viremic rats were 76.3-100% identical to each other in an 840-nucleotide sequence and 75.4-88.4% identical to the rat HEV strains reported in Germany and Vietnam. Five representative Indonesian strains, one from each of five phylogenetic clusters, whose entire genomic sequence was determined, were segregated into three genetic groups (a German type, Vietnamese type and novel type), which differed from each other by 19.5-23.5 (22.0 ± 1.7)% over the entire genome. These results suggest the presence of at least three genetic groups of rat HEV and indicate the circulation of polyphyletic strains of rat HEV belonging to three distinct genetic groups in Indonesia.
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Affiliation(s)
- Mulyanto
- West Nusa Tenggara Hepatitis Laboratory, Mataram, Indonesia; Immunobiology Laboratory, Faculty of Medicine, University of Mataram, Mataram, Indonesia
| | | | | | - Khalid
- Immunobiology Laboratory, Faculty of Medicine, University of Mataram, Mataram, Indonesia
| | - Masaharu Takahashi
- Division of Virology, Department of Infection and Immunity, Jichi Medical University School of Medicine, 3311-1 Yakushiji, Shimotsuke-Shi, Tochigi-Ken 329-0498, Japan
| | - Hiroshi Ohnishi
- Division of Virology, Department of Infection and Immunity, Jichi Medical University School of Medicine, 3311-1 Yakushiji, Shimotsuke-Shi, Tochigi-Ken 329-0498, Japan
| | - Suljid Jirintai
- Division of Virology, Department of Infection and Immunity, Jichi Medical University School of Medicine, 3311-1 Yakushiji, Shimotsuke-Shi, Tochigi-Ken 329-0498, Japan
| | - Shigeo Nagashima
- Division of Virology, Department of Infection and Immunity, Jichi Medical University School of Medicine, 3311-1 Yakushiji, Shimotsuke-Shi, Tochigi-Ken 329-0498, Japan
| | - Tsutomu Nishizawa
- Division of Virology, Department of Infection and Immunity, Jichi Medical University School of Medicine, 3311-1 Yakushiji, Shimotsuke-Shi, Tochigi-Ken 329-0498, Japan
| | - Hiroaki Okamoto
- Division of Virology, Department of Infection and Immunity, Jichi Medical University School of Medicine, 3311-1 Yakushiji, Shimotsuke-Shi, Tochigi-Ken 329-0498, Japan.
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Ma H, Geng Y, Li Z, Harrison TJ, Huang W, Zhao C, Wang Y. Analysis of the complete genome sequences of one swine and two human hepatitis E virus genotype 4 strains isolated in Beijing, China. INFECTION GENETICS AND EVOLUTION 2013; 18:42-7. [PMID: 23684630 DOI: 10.1016/j.meegid.2013.04.038] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/12/2012] [Revised: 04/26/2013] [Accepted: 04/29/2013] [Indexed: 12/28/2022]
Abstract
Full-length sequences were determined and analyzed for two human (MO and W3) and one swine (W2-5) hepatitis E virus (HEV) isolates from Beijing, China. The genomes of the three strains were composed of 7242, 7239, 7239 nucleotides, respectively, excluding the poly (A) tails, and were 84% identical to each other. All were classified into genotype 4. Sequence analysis shows that the 2 human isolates have up to 91-94% nucleotide identity in full length genome with swine strains isolated in China, while the swine isolate share 92% identity with the human strain T1 from Beijing. At the amino acid level, the three strains share 94%, 97% and 89-92% identity in the ORF1, ORF2 and ORF3, proteins respectively. The human strains MO and W3 have the highest identity, 97%, 98-99% and 96-98% in ORFs 1-3, respectively, to swine strains CHN-XJ-SW13 and CHN-XJ-SW33 from Xinjiang, China, while swine strain W2-5 has highest identity with the human strain HE-JA2, 96%, 99% and 91% in ORFs 1-3, respectively. Genotype specific amino acid substitutions were found at a single site in all three ORFs by sequences alignment, and genotype specific short sequences (5-10aa in length) were found in ORF1 and the C-terminus of ORF3. However, no difference was found at any amino acid position that discriminates between human and swine HEVs within genotype 4 for any of the three ORFs. These results indicated that the genotype 4 HEV strains from humans and pigs in China may evolve from the common ancestor.
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Affiliation(s)
- Hongxia Ma
- Department of Cell Biology, National Institutes for Food and Drug Control, No. 2, Tiantanxili, Beijing 100050, China
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Abstract
The classification of hepatitis E virus (HEV) variants is currently in transition without agreed definitions for genotypes and subtypes or for deeper taxonomic groupings into species and genera that could incorporate more recently characterized viruses assigned to the Hepeviridae family that infect birds, bats, rodents, and fish. These conflicts arise because of differences in the viruses and genomic regions compared and in the methodology used. We have reexamined published sequences and found that synonymous substitutions were saturated in comparisons between and within virus genotypes. Analysis of complete genome sequences or concatenated ORF1/ORF2 amino acid sequences indicated that HEV variants most closely related to those infecting humans can be consistently divided into six genotypes (types 1 to 4 and two additional genotypes from wild boar). Variants isolated from rabbits, closely related to genotype 3, occupy an intermediate position. No consistent criteria could be defined for the assignment of virus subtypes. Analysis of amino acid sequences from these viruses with the more divergent variants from chickens, bats, and rodents in three conserved subgenomic regions (residues 1 to 452 or 974 to 1534 of ORF1 or residues 105 to 458 of ORF2) provided consistent support for a division into 4 groups, corresponding to HEV variants infecting humans and pigs, those infecting rats and ferrets, those from bats, and those from chickens. This approach may form the basis for a future genetic classification of HEV into four species, with the more divergent HEV-like virus from fish (cutthroat trout virus) representing a second genus.
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Kaba M, Moal V, Gérolami R, Colson P. Epidemiology of mammalian hepatitis E virus infection. Intervirology 2013; 56:67-83. [PMID: 23343760 DOI: 10.1159/000342301] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2011] [Accepted: 07/28/2012] [Indexed: 12/26/2022] Open
Abstract
Mammalian hepatitis E virus (HEV), the etiological agent of hepatitis E in humans, is a recently discovered infectious agent. It was identified for the first time in 1983 using electron microscopy on a faecal specimen of a person infected with non-A, non-B enterically-transmitted hepatitis. Based on retrospective and prospective studies, HEV was long described as one of the leading causes of acute viral hepatitis in tropical and subtropical countries, whereas in developed countries hepatitis E was considered an imported disease from HEV hyperendemic countries. Data from studies conducted during the past decade have greatly shifted our knowledge on the epidemiology and clinical spectrum of HEV. Recently, it has been shown that contrary to previous beliefs, hepatitis E is also an endemic disease in several developed countries, particularly in Japan and in Europe, as evidenced by reports of high anti-HEV immunoglobulin G prevalence in healthy individuals and an increasing number of non-travel-related acute hepatitis E cases. Moreover, a porcine reservoir and growing evidence of zoonotic transmission have been reported in these countries. This review summarizes the current knowledge on the epidemiology and prevention of transmission of mammalian HEV.
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Affiliation(s)
- Mamadou Kaba
- Aix-Marseille Université, URMITE UM63 CNRS 7278 IRD 198 INSERM U1095, IHU Méditerranée Infection, Facultés de Médecine et de Pharmacie, Marseille, France
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26
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Rodríguez-Frias F, Jardi R, Buti M. [Hepatitis E: molecular virology, epidemiology and pathogenesis]. Enferm Infecc Microbiol Clin 2012; 30:624-634. [PMID: 22386306 DOI: 10.1016/j.eimc.2012.01.014] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2011] [Revised: 01/11/2012] [Accepted: 01/18/2012] [Indexed: 02/07/2023]
Abstract
Hepatitis E represents a significant proportion of enteric transmitted liver diseases and poses a major public health problem, mainly associated with epidemics due to contamination of water supplies, especially in developing countries. Hepatitis E virus (HEV) is responsible for self-limiting acute liver oral-faecal infections. In industrialised countries, acute hepatitis E is sporadic, detected in travellers from endemic areas but also in sporadic cases with no risk factors. HEV is a non-enveloped virus with a single-stranded RNA genome classified into 4 genotypes and a single serotype. Genotypes 1 and 2 only infect humans, and are predominant in the developing countries, while 3 and 4 are predominant in industrialised countries, and also infect other species of mammals, especially pigs, and multiple evidence classifies HEV as a zoonotic agent. Some HEV chronic infections have recently been reported in kidney and liver transplant patients. The mortality rate of HEV infection is greater than hepatitis A. In addition to faecal-oral transmission, parenteral transmission of HEV has also been reported. Several vaccines are currently in development. The severity of this infection in some groups of patients, especially pregnant women, and the occurrence of chronic hepatitis, even with progression to cirrhosis, have raised interest in the application of interferon and/or ribavirin therapy.
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Affiliation(s)
- Francisco Rodríguez-Frias
- Unidad de Proteínas Hepatitis, Servicio de Bioquímica, Hospital Universitario Vall d'Hebron, Barcelona, España.
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27
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Bouquet J, Tessé S, Lunazzi A, Eloit M, Rose N, Nicand E, Pavio N. Close similarity between sequences of hepatitis E virus recovered from humans and swine, France, 2008-2009. Emerg Infect Dis 2012; 17:2018-25. [PMID: 22099089 PMCID: PMC3311115 DOI: 10.3201/eid1711.110616] [Citation(s) in RCA: 86] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023] Open
Affiliation(s)
- Jérôme Bouquet
- Anses, Laboratoire de Santé Animale, Maisons-Alfort, France
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28
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Identical consensus sequence and conserved genomic polymorphism of hepatitis E virus during controlled interspecies transmission. J Virol 2012; 86:6238-45. [PMID: 22457521 DOI: 10.1128/jvi.06843-11] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
High-throughput sequencing of bile and feces from two pigs experimentally infected with human hepatitis E virus (HEV) of genotype 3f revealed the same full-length consensus sequence as in the human sample. Twenty-nine percent of polymorphic sites found in HEV from the human sample were conserved throughout the infection of the heterologous host. The interspecies transmission of HEV quasispecies is the result of a genomic negative-selection pressure on random mutations which can be deleterious to the viral population. HEV intrahost nucleotide diversity was found to be in the lower range of other human RNA viruses but correlated with values found for zoonotic viruses. HEV transmission between humans and pigs does not seem to be modulated by host-specific mutations, suggesting that adaptation is mainly regulated by ecological drivers.
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29
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Moal V, Gerolami R, Colson P. First human case of co-infection with two different subtypes of hepatitis E virus. Intervirology 2012; 55:484-7. [PMID: 22398950 DOI: 10.1159/000335664] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2011] [Accepted: 12/01/2011] [Indexed: 01/19/2023] Open
Abstract
Hepatitis E virus (HEV), the main etiologic agent of enterically transmitted acute hepatitis in developing countries, is now recognized as an emerging agent of autochthonous disease and chronic hepatitis E in immunocompromised patients in Europe where HEV infection is probably zoonotically acquired. We describe the first human case of acute HEV infection with two genotype 3 viruses in a French kidney transplant recipient, probably acquired through consumption of uncooked pig liver sausage (figatellu). The patient presented two viral sequences nearly identical to sequences recovered from figatelli. Autochthonous co-infections with different genotype 3 HEV strains can occur in our geographical area.
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Affiliation(s)
- Valérie Moal
- Centre de Néphrologie et Transplantation Rénale, Hôpital Conception, Assistance Publique des Hôpitaux de Marseille, Aix-Marseille Université, Marseille, France.
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30
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Kamal SM, Mahmoud S, Hafez T, EL-Fouly R. Viral hepatitis a to e in South mediterranean countries. Mediterr J Hematol Infect Dis 2010; 2:e2010001. [PMID: 21415943 PMCID: PMC3033107 DOI: 10.4084/mjhid.2010.001] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2010] [Accepted: 02/04/2010] [Indexed: 02/06/2023] Open
Abstract
Viral hepatitis represents an important health problem in the South Mediterranean countries, Egypt, Libya, Tunisia, Algeria and Morocco. Emerging natural history and epidemiological information reveal differences in the overall epidemiology, risk factors and modes of transmission of viral hepatitis A, B, C, D, E infections in the South Mediterranean region. The differences in the in incidence and prevalence of viral hepatitis across North African countries is attributed to variations in health care and sanitation standards, risk factors and immunization strategies. The active continuous population movement through travel, tourism and migration from and to the South Mediterranean countries contribute to the spread of infections due to hepatitis viruses across borders leading to outbreaks and emergence of new patterns of infection or introduction of uncommon genotypes in other countries, particularly in Europe.
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Affiliation(s)
- Sanaa M. Kamal
- Department of Tropical Medicine, Gastroenterology and Liver Disease, Ain Shams University, Cairo, Egypt
| | - Sara Mahmoud
- Department of Tropical Medicine, Gastroenterology and Liver Disease, Ain Shams University, Cairo, Egypt
| | - Tamer Hafez
- Department of Tropical Medicine, Gastroenterology and Liver Disease, Ain Shams University, Cairo, Egypt
| | - Runia EL-Fouly
- Department of Tropical Medicine, Gastroenterology and Liver Disease, Ain Shams University, Cairo, Egypt
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31
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Inhibition of Hepatitis E virus replication using short hairpin RNA (shRNA). Antiviral Res 2010; 85:541-50. [PMID: 20105445 DOI: 10.1016/j.antiviral.2010.01.005] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2009] [Revised: 01/04/2010] [Accepted: 01/20/2010] [Indexed: 02/07/2023]
Abstract
Hepatitis E virus (HEV) is a non-enveloped, single-stranded, positive sense RNA virus, which is a major cause of water-borne hepatitis. RNA interference (RNAi) is a sequence-specific cellular antiviral defence mechanism, induced by double-stranded RNA, which we used to investigate knockdown of several genes and the 3' cis-acting element (CAE) of HEV. In the present report, shRNAs were developed against the putative helicase and replicase domains and the 3'CAE region of HEV. Production of siRNA was confirmed by northern hybridization. The possible innate response induction due to shRNA expressions was verified by transcript analysis for interferon-beta and 2',5'-oligoadenylate synthetase genes and was found to be absent. Initially, the selected shRNAs were tested for their efficiency against the respective genes/3'CAE using inhibition of fused viral subgenomic target domain-renilla luciferase reporter constructs. The effective shRNAs were studied for their inhibitory effects on HEV replication in HepG2 cells using HEV replicon and reporter replicon. RNAi mediated silencing was demonstrated by reduction of luciferase activity in subgenomic target-reporter constructs and reporter replicon. The real time PCR was used to demonstrate inhibition of native replicon replication in transfected cells. Designed shRNAs were found to be effective in inhibiting virus replication to a variable extent (45-93%).
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32
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Kobayashi Y, Suzuki Y, Itou T, Carvalho AAB, Cunha EMS, Ito FH, Gojobori T, Sakai T. Low genetic diversities of rabies virus populations within different hosts in Brazil. INFECTION GENETICS AND EVOLUTION 2009; 10:278-83. [PMID: 20018256 DOI: 10.1016/j.meegid.2009.12.003] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/11/2009] [Revised: 12/03/2009] [Accepted: 12/05/2009] [Indexed: 01/21/2023]
Abstract
The low rates of nonsynonymous evolution observed in natural rabies virus (RABV) isolates are suggested to have arisen in association with the structural and functional constraints operating on the virus protein and the infection strategies employed by RABV within infected hosts to avoid strong selection by the immune response. In order to investigate the relationship between the genetic characteristics of RABV populations within hosts and the virus evolution, the present study examined the genetic heterogeneities of RABV populations within naturally infected dogs and foxes in Brazil, as well as those of bat RABV populations that were passaged once in suckling mice. Sequence analyses of complete RABV glycoprotein (G) genes showed that RABV populations within infected hosts were genetically highly homogeneous whether they were infected naturally or experimentally (nucleotide diversities of 0-0.95x10(-3)). In addition, amino acid mutations were randomly distributed over the entire region of the G protein, and the nonsynonymous/synonymous rate ratios (d(N)/d(S)) for the G protein gene were less than 1. These findings suggest that the low genetic diversities of RABV populations within hosts reflect the stabilizing selection operating on the virus, the infection strategies of the virus, and eventually, the evolutionary patterns of the virus.
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Affiliation(s)
- Yuki Kobayashi
- Nihon University Veterinary Research Center, 1866 Kameino, Fujisawa, Kanagawa 252-8510, Japan
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33
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Chandra V, Taneja S, Kalia M, Jameel S. Molecular biology and pathogenesis of hepatitis E virus. J Biosci 2009; 33:451-64. [PMID: 19208971 DOI: 10.1007/s12038-008-0064-1] [Citation(s) in RCA: 134] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
The hepatitis E virus (HEV) is a small RNA virus and the etiological agent for hepatitis E, a form of acute viral hepatitis. The virus has a feco-oral transmission cycle and is transmitted through environmental contamination, mainly through drinking water. Recent studies on the isolation of HEV-like viruses from animal species also suggest zoonotic transfer of the virus. The absence of small animal models of infection and efficient cell culture systems has precluded virological studies on the replication cycle and pathogenesis of HEV. A vaccine against HEV has undergone successful clinical testing and diagnostic tests are available. This review describes HEV epidemiology, clinical presentation, pathogenesis, molecular virology and the host response to HEV infection. The focus is on published literature in the past decade.
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Affiliation(s)
- Vivek Chandra
- Virology Group, International Centre for Genetic Engineering and Biotechnology (ICGEB), New Delhi 110 067, India
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34
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Bilic I, Jaskulska B, Basic A, Morrow CJ, Hess M. Sequence analysis and comparison of avian hepatitis E viruses from Australia and Europe indicate the existence of different genotypes. J Gen Virol 2009; 90:863-873. [PMID: 19264623 DOI: 10.1099/vir.0.007179-0] [Citation(s) in RCA: 92] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
Avian hepevirus infections were detected in chickens suffering from big liver and spleen disease or hepatitis-splenomegaly syndrome in Australia, the USA and Europe. Available data indicate their genetic relationship to mammalian hepatitis E virus (HEV). In the present study, the near-complete genomic sequences of an Australian and a European isolate of avian hepatitis E virus (avian HEV) are reported for the first time. Furthermore, the phylogenetic relationship to other avian HEVs is determined. Sequence analyses of these isolates identified major genetic differences among avian HEVs. Most of them are located within the open reading frame (ORF)1 region, although only a few lie within conserved motifs of predicted domains. Non-silent mutations in the ORF2 region suggest the presence of potentially different epitopes among avian HEV isolates. Finally, phylogenetic analysis confirmed the distant relationship to mammalian HEV and additionally suggested that the avian HEVs can be separated into three different genotypes: 1 (Australia), 2 (USA) and 3 (Europe), indicating a geographical distribution pattern.
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Affiliation(s)
- Ivana Bilic
- Clinic for Avian, Reptile and Fish Medicine, Department for Farm Animals and Veterinary Public Health, University of Veterinary Medicine, Vienna, Austria
| | - Barbara Jaskulska
- Clinic for Avian, Reptile and Fish Medicine, Department for Farm Animals and Veterinary Public Health, University of Veterinary Medicine, Vienna, Austria
| | - Ana Basic
- Clinic for Avian, Reptile and Fish Medicine, Department for Farm Animals and Veterinary Public Health, University of Veterinary Medicine, Vienna, Austria
| | | | - Michael Hess
- Clinic for Avian, Reptile and Fish Medicine, Department for Farm Animals and Veterinary Public Health, University of Veterinary Medicine, Vienna, Austria
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35
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Pelosi E, Clarke I. Hepatitis E: a complex and global disease. EMERGING HEALTH THREATS JOURNAL 2008; 1:e8. [PMID: 22460217 PMCID: PMC3167588 DOI: 10.3134/ehtj.08.008] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/12/2007] [Revised: 03/12/2008] [Accepted: 04/10/2008] [Indexed: 12/13/2022]
Abstract
Thirty years after its discovery, the hepatitis E virus (HEV) continues to represent a major public health problem in developing countries. In developed countries, it has emerged as a significant cause of non-travel-associated acute hepatitis. HEV infects a wide range of mammalian species and a key reservoir worldwide appears to be swine. Genomic sequence similarity between some human HEV genotypes and swine HEV strains has been identified and we know that humans can acquire HEV infection from animals. Although for the most part the clinical course of HEV infection is asymptomatic or mild, significant risk of serious disease exists in pregnant women and those with chronic liver disease. In addition, there are data on the threat of chronic infections in immunocompromised patients. Beyond management of exposure by public health measures, recent data support that active immunisation can prevent hepatitis E, highlighting the need for vaccination programmes. Here we review the current knowledge on HEV, its epidemiology, and the management and prevention of human disease.
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Affiliation(s)
- E Pelosi
- Department of Microbiology and Virology, Health Protection Agency, Southeast Regional Laboratory, Southampton General Hospital, Southampton, UK
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36
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Bosch A, Guix S, Sano D, Pintó RM. New tools for the study and direct surveillance of viral pathogens in water. Curr Opin Biotechnol 2008; 19:295-301. [PMID: 18508257 PMCID: PMC7126527 DOI: 10.1016/j.copbio.2008.04.006] [Citation(s) in RCA: 151] [Impact Index Per Article: 8.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2008] [Revised: 04/14/2008] [Accepted: 04/17/2008] [Indexed: 12/05/2022]
Abstract
Half a century ago scientists attempted the detection of poliovirus in water. Since then other enteric viruses responsible for gastroenteritis and hepatitis have replaced enteroviruses as the main target for detection. However, most viral outbreaks are restricted to norovirus and hepatitis A virus, making them the main targets in water. The inclusion of virus analysis in regulatory standards for viruses in water samples must overcome several shortcomings such as the technical difficulties and high costs of virus monitoring, the lack of harmonised and standardised assays and the challenge posed by the ever-changing nature of viruses. However, new tools are nowadays available for the study and direct surveillance of viral pathogens in water that may contribute to fulfil these requirements.
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Affiliation(s)
- Albert Bosch
- Enteric Virus Laboratory, Department of Microbiology, University of Barcelona, Spain.
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37
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Renou C, Cadranel JF, Bourlière M, Halfon P, Ouzan D, Rifflet H, Carenco P, Harafa A, Bertrand JJ, Boutrouille A, Muller P, Igual JP, Decoppet A, Eloit M, Pavio N. Possible zoonotic transmission of hepatitis E from pet pig to its owner. Emerg Infect Dis 2008; 13:1094-6. [PMID: 18214190 PMCID: PMC2878240 DOI: 10.3201/eid1307.070063] [Citation(s) in RCA: 67] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023] Open
Abstract
Hepatitis E is transmitted mainly by water or food, but in industrialized countries, all routes of transmission have not been identified. We describe possible zoonotic transmission of hepatitis E virus that involved direct contact between a pet pig and its owner.
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38
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Jiménez de Oya N, Escribano-Romero E, Blázquez AB, Saiz JC. [Hepatitis E virus: zoonotic implications]. GASTROENTEROLOGIA Y HEPATOLOGIA 2008; 30:408-18. [PMID: 17692200 DOI: 10.1157/13108819] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
The Hepatitis E virus (HEV) is transmitted primarily by the feco-oral route throughout contaminated water and/or food, and is one of the main causes of acute hepatitis worldwide. Hepatitis E shows a high mobility but a low mortality rate, except in pregnant women, where it can be as high as 30%. HEV causes sporadic cases and epidemic outbreaks, mainly in Africa, Asia and Central America. In Europe, there is an increase in the number of reported autochthonous cases no related with travel to endemic areas. In addition, HEV also infects animals, including pigs, and its zoonotic potential has been recently demonstrated. In fact, porcine and human strains of the same area are genetically more closely related to each other than to strains of the same species but a different geographical region, and there are data suggesting that people in close contact with pigs presents a higher prevalence of specific anti-HEV antibodies. All together, these data have drove to an increase interest in determining the incidence of the disease in animals, its possible zoonotic risk, and its implications for human health. In the present article we revised the current knowledge about HEV, with special emphasis in the possible consequences of its zoonotic potential.
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Affiliation(s)
- Nereida Jiménez de Oya
- Laboratorio de Zoonosis y Virología Medioambiental, Departamento de Biotecnología, Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA), Madrid, España
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39
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Quer J, Martell M, Rodriguez F, Bosch A, Jardi R, Buti M, Esteban J. The Impact of Rapid Evolution of Hepatitis Viruses. ORIGIN AND EVOLUTION OF VIRUSES 2008:303-349. [DOI: 10.1016/b978-0-12-374153-0.00015-1] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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40
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Okamoto H. Genetic variability and evolution of hepatitis E virus. Virus Res 2007; 127:216-28. [PMID: 17363102 DOI: 10.1016/j.virusres.2007.02.002] [Citation(s) in RCA: 255] [Impact Index Per Article: 14.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2006] [Revised: 01/13/2007] [Accepted: 02/03/2007] [Indexed: 01/14/2023]
Abstract
Hepatitis E virus (HEV) is the sole member of the genus Hepevirus in the family Hepeviridae. HEV is transmitted primarily by the fecal-oral route, and water-borne epidemics are characteristic of hepatitis E in many developing countries in Asia, Africa and Latin America where sanitation conditions are suboptimal. Accumulating lines of evidence indicate that HEV-associated hepatitis also occurs domestically among individuals in industrialized countries, that there are animal reservoirs of HEV such as domestic pigs and wild boars, and that hepatitis E is a zoonosis. Based on the extensive genomic variability among HEV isolates, HEV sequences have been classified into four genotypes: genotype 1 consists of epidemic strains in developing countries in Asia and Africa; genotype 2 has been described in Mexico and several African countries; genotype 3 HEV is widely distributed and has been isolated from sporadic cases of acute hepatitis E and/or domestic pigs in many countries in the world, except for countries in Africa; and genotype 4 contains strains isolated from humans and/or domestic pigs exclusively in Asian countries. This paper reviews current knowledge on the genomic variability, geographic distribution and zoonotic aspects of HEV as well as the clinical significance of genotype and evolution of HEV.
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Affiliation(s)
- Hiroaki Okamoto
- Division of Virology, Department of Infection and Immunity, Jichi Medical University, School of Medicine, Tochigi-Ken 329-0498, Japan.
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41
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Albetkova A, Drobeniuc J, Yashina T, Musabaev E, Robertson B, Nainan O, Favorov M. Characterization of hepatitis E virus from outbreak and sporadic cases in Turkmenistan. J Med Virol 2007; 79:1696-702. [PMID: 17854031 DOI: 10.1002/jmv.20991] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022]
Abstract
Large outbreaks and sporadic cases of hepatitis E have been reported in Central Asia. We assessed the genetic relatedness of hepatitis E virus (HEV) strains from outbreak and sporadic cases in Turkmenistan. Specimens from outbreak and sporadic cases of acute hepatitis non-A, non-B were tested by reverse transcription (RT)-polymerase chain reaction (PCR) to identify the presence of HEV RNA; nucleotide sequences were analyzed. HEV RNA was detected from 23/156 (15%) outbreak cases and 2/23 (9%) sporadic cases. The HEV outbreak isolates represented 14 unique sequences with genetic distances varying between 0.3% and 8.6%, 12 of which were closely related, with distances between 0.3% and 5.6%. Two unique sequences from outbreak cases 32 and 42 were closely related (99.7%) and shared 91.8-93.4% of sequence with the other 12 strains. The two strains were closely related to the previously published isolates from Burma (99.7-100%) and India-Madras (95.7-96.1%). The two 1994 sporadic HEV strains were 97.4% distinct, wile revealing 91.4-94.1% homology to 1985 strains, and 94.4-94.7% to HEV from the neighboring China and Pakistan. Genetic diversity of HEV that caused the hepatitis E outbreak in Turkmenistan in 1985 suggests heterogeneity of viral sources. Sporadic hepatitis E that occurred in 1994 was caused by viral strains genetically distinct from those causing the outbreak in 1985, yet closely related to HEV from neighboring countries. The study suggests that circulation of a broad variety of strains of HEV may occur in Central Asia, regardless of international borders, presenting a significant public health threat to the population of the region.
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Affiliation(s)
- Adilya Albetkova
- CDC Central Asia Office, Division of International Health, Office of Global Health, Centers for Disease Control and Prevention, Atlanta, Georgia
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42
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Dong C, Dai X, Shao JS, Hu K, Meng JH. Identification of genetic diversity of hepatitis E virus (HEV) and determination of the seroprevalence of HEV in eastern China. Arch Virol 2006; 152:739-46. [PMID: 17131064 DOI: 10.1007/s00705-006-0882-0] [Citation(s) in RCA: 33] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2006] [Accepted: 10/23/2006] [Indexed: 01/02/2023]
Abstract
Hepatitis E, caused by the hepatitis E virus (HEV), is endemic in China. However, the molecular characteristics of HEV circulating in eastern China and the seroprevalence of HEV infection in eastern China are relatively unknown. In this study, 25 HEV strains, isolated from sporadic hepatitis E cases in eastern China, were sequenced in the RNA-dependent RNA polymerase region and subjected to phylogenetic analysis. These HEV strains were 74.6-98.7% identical in nucleotides and were all clustered into HEV genotype 4. Most of them formed new sub-genotypes and revealed a high degree of genetic variance. In addition, 12,052 serum samples were collected from people of different ages, living in urban or rural areas in eastern China. Anti-HEV IgG activity was detected in 2073 (17.20%). The prevalence of anti-HEV IgG significantly increased with age (P<0.0001), ranging from 7.92% in children (<10 years old) to 21.48% among older persons (>or=60 years old). Moreover, statistical analysis showed that there was a significant difference between rural and urban areas, with higher prevalence for people living in rural neighborhoods (P<0.001).
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Affiliation(s)
- C Dong
- Department of Microbiology and Immunology, School of Medicine, Southeast University, Nanjing, China
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43
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Vabret A, Dina J, Mourez T, Gouarin S, Petitjean J, van der Werf S, Freymuth F. Inter- and intra-variant genetic heterogeneity of human coronavirus OC43 strains in France. J Gen Virol 2006; 87:3349-3353. [PMID: 17030869 DOI: 10.1099/vir.0.82065-0] [Citation(s) in RCA: 18] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022] Open
Abstract
Human coronavirus OC43 (HCoV-OC43) causes acute, self-limited respiratory infections. A close relationship between bovine coronaviruses (BCoVs) and HCoV-OC43 has recently been demonstrated. This study includes seven clinical, non-cell culture-adapted, contemporary HCoV-OC43 strains detected in France in 2003. By using RT-PCR and clonal sequencing of the S1 gene of HCoV-OC43, the inter-variant heterogeneity of the HCoV-OC43 circulating strains was studied and the intra-variant diversity was assessed by investigation of a quasispecies cloud. This paper brings to the forefront a high genetic diversity of circulating HCoV-OC43 variants. Genetically different groups are defined among the variants described in this study. One of these variants holds characteristics of an outlier and presents a deletion of 12 nt, also found in BCoV strains. Moreover, the presence of HCoV-OC43 as a quasispecies cloud in vivo during an acute respiratory-tract illness was discovered. It has also been revealed that quasispecies-cloud sizes are similar for the two viral populations tested.
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Affiliation(s)
- Astrid Vabret
- Laboratory of Virology, University Hospital of Caen, Avenue Georges Clemenceau, 14033 Caen cedex, France
| | - Julia Dina
- Laboratory of Virology, University Hospital of Caen, Avenue Georges Clemenceau, 14033 Caen cedex, France
| | - Thomas Mourez
- Laboratory of Virology, University Hospital of Caen, Avenue Georges Clemenceau, 14033 Caen cedex, France
| | - Stéphanie Gouarin
- Laboratory of Virology, University Hospital of Caen, Avenue Georges Clemenceau, 14033 Caen cedex, France
| | - Joëlle Petitjean
- Laboratory of Virology, University Hospital of Caen, Avenue Georges Clemenceau, 14033 Caen cedex, France
| | - Sylvie van der Werf
- Laboratoire de Génétique Moléculaire des Virus Respiratoires, Institut Pasteur, 25-28 rue du Docteur Roux, 75015 Paris, France
| | - François Freymuth
- Laboratory of Virology, University Hospital of Caen, Avenue Georges Clemenceau, 14033 Caen cedex, France
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44
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Tolari F, Chiaro LD, Card R, Mazzei M, Bandecchi P, Banks M. Phylogenetic Study of Viral Isolates of Swine and Human Hepatitis E Virus. Vet Res Commun 2006. [DOI: 10.1007/s11259-006-0059-z] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
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Lu L, Li C, Hagedorn CH. Phylogenetic analysis of global hepatitis E virus sequences: genetic diversity, subtypes and zoonosis. Rev Med Virol 2006; 16:5-36. [PMID: 16175650 DOI: 10.1002/rmv.482] [Citation(s) in RCA: 592] [Impact Index Per Article: 31.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Nucleotide sequences from a total of 421 HEV isolates were retrieved from Genbank and analysed. Phylogenetically, HEV was classified into four major genotypes. Genotype 1 was more conserved and classified into five subtypes. The number of genotype 2 sequences was limited but can be classified into two subtypes. Genotypes 3 and 4 were extremely diverse and can be subdivided into ten and seven subtypes. Geographically, genotype 1 was isolated from tropical and several subtropical countries in Asia and Africa, and genotype 2 was from Mexico, Nigeria, and Chad; whereas genotype 3 was identified almost worldwide including Asia, Europe, Oceania, North and South America. In contrast, genotype 4 was found exclusively in Asia. It is speculated that genotype 3 originated in the western hemisphere and was imported to several Asian countries such as Japan, Korea and Taiwan, while genotype 4 has been indigenous and likely restricted to Asia. Genotypes 3 and 4 were not only identified in swine but also in wild animals such as boar and a deer. Furthermore, in most areas where genotypes 3 and 4 were characterised, sequences from both humans and animals were highly conserved, indicating they originated from the same infectious sources. Based upon nucleotide differences from five phylogenies, it is proposed that five, two, ten and seven subtypes for HEV genotypes 1, 2, 3 and 4 be designated alphabetised subtypes. Accordingly, a total of 24 subtypes (1a, 1b, 1c, 1d, 1e, 2a, 2b, 3a, 3b, 3c, 3d, 3e, 3f, 3g, 3h, 3i, 3j, 4a, 4b, 4c, 4d, 4e, 4f and 4g) were given.
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Affiliation(s)
- Ling Lu
- Division of Gastroenterology/Hepatology, Department of Medicine, Kansas University Medical Center, Kansas City, Kansas 66160, USA.
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Nicand E, Armstrong GL, Enouf V, Guthmann JP, Guerin JP, Caron M, Nizou JY, Andraghetti R. Genetic heterogeneity of hepatitis E virus in Darfur, Sudan, and neighboring Chad. J Med Virol 2006; 77:519-21. [PMID: 16254969 DOI: 10.1002/jmv.20487] [Citation(s) in RCA: 50] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
The within-outbreak diversity of hepatitis E virus (HEV) was studied during the outbreak of hepatitis E that occurred in Sudan in 2004. Specimens were collected from internally displaced persons living in a Sudanese refugee camp and two camps implanted in Chad. A comparison of the sequences in the ORF2 region of 23 Sudanese isolates and five HEV samples from the two Chadian camps displayed a high similarity (>99.7%) to strains belonging to Genotype 1. But four isolates collected in one of the Chadian camps were close to Genotype 2. Circulation of divergent strains argues for possible multiple sources of infection.
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Affiliation(s)
- Elisabeth Nicand
- National Reference Centre for Hepatitis E, Teaching Military Hospital Val de Grâce, Paris, France.
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