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Hepatitis E Virus Molecular Epidemiology and Evolution

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A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "Animal Viruses".

Deadline for manuscript submissions: closed (31 December 2020) | Viewed by 20799

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Special Issue Editor

Prof. Helene Norder

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Guest Editor

Department of Clinical Microbiology- Virology, Sahlgrenska University Hospital – Sahlgrenska Academy, Guldhedsg 10B, 413 45 Gothenburg, Sweden
Interests: hepatitis viruses; picornaviruses; virus evolution; molecular epidemiology

Special Issue Information

Dear Colleagues,

Even if much progress has been achieved in our understanding of hepatitis E virus (HEV), many gaps in our knowledge remain. HEV has a broad host range being isolated from fish, birds, and mammals, such as bats, rodents, ungulates, and humans. Most likely, other vertebrate hosts still remain to be identified. Viruses belonging to the same genus have the potential to cross species barriers, apart from HEV1 and HEV2, which only infect humans. These two types, which cause large waterborne outbreaks with high mortality rates in the pregnant female, are also associated with pancreatitis. HEV3 and HEV4 also infect humans with pigs as their natural hosts and are thus zoonotic. Human infections by HEV3 and 4 may in addition to acute or chronic hepatitis also cause different extrahepatic manifestations, in particular neurological illnesses.

The virus is mostly transmitted by the fecal–oral route, but vertical transmission through contaminated blood products also occurs. Water may be a source of infection, not only for HEV1 and 2, but also for HEV3, which has been detected in drinking water. However, ingestion of contaminated pork is probably the major route for HEV3 and 4 infections, although other so-far unidentified routes may also exist.

In this Special Issue of Viruses, we welcome research papers, short communications, and reviews in the field of HEV research. The scope is to assemble an up-to-date view on molecular epidemiology and evolution of HEV, including the HEV life cycle, host range and host–pathogen interactions, transmission, disease manifestations, treatment, and prevention.

Prof. Helene Norder
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Viruses is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

hepatitis E virus
HEV
molecular epidemiology of HEV
evolution of HEV
HEV life cycle
HEV host range
HEV transmission
host–HEV interactions
disease manifestations of HEV infections
treatment and prevention of HEV

Published Papers (7 papers)

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Research

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9 pages, 2712 KiB

Open AccessArticle

Comparison of Hepatitis E Virus Sequences from Humans and Swine, The Netherlands, 1998–2015

by Boris M. Hogema, Renate W. Hakze-van der Honing, Michel Molier, Hans L. Zaaijer and Wim H. M. van der Poel

Viruses 2021, 13(7), 1265; https://doi.org/10.3390/v13071265 - 29 Jun 2021

Cited by 6 | Viewed by 1938

Abstract

Pigs are suspected to be a major source of zoonotic hepatitis E virus (HEV) infection in industrialized countries, but the transmission route(s) from pigs to humans are ill-defined. Sequence comparison of HEV isolates from pigs with those from blood donors and patients in 372 samples collected in The Netherlands in 1998 and 1999 and between 2008 and 2015 showed that all sequences were genotype 3 except for six patients (with travel history). Subgenotype 3c (gt3c) was the most common subtype. While the proportion of gt3c increased significantly between 1998 and 2008, it remained constant between 2008 and 2015. Among the few circulating HEV subtypes, there was no difference observed between the human and the pig isolates. Hepatitis E viruses in humans are very likely to originate from pigs, but it is unclear why HEV gt3c has become the predominant subtype in The Netherlands. Full article

(This article belongs to the Special Issue Hepatitis E Virus Molecular Epidemiology and Evolution)

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19 pages, 3299 KiB

Open AccessArticle

Characterization of a Cell Culture System of Persistent Hepatitis E Virus Infection in the Human HepaRG Hepatic Cell Line

by Marie Pellerin, Edouard Hirchaud, Yannick Blanchard, Nicole Pavio and Virginie Doceul

Viruses 2021, 13(3), 406; https://doi.org/10.3390/v13030406 - 4 Mar 2021

Cited by 8 | Viewed by 2077

Abstract

Hepatitis E virus (HEV) is considered as an emerging global health problem. In most cases, hepatitis E is a self-limiting disease and the virus is cleared spontaneously without the need of antiviral therapy. However, immunocompromised individuals can develop chronic infection and liver fibrosis that can progress rapidly to cirrhosis and liver failure. The lack of efficient and relevant cell culture system and animal models has limited our understanding of the biology of HEV and the development of effective drugs for chronic cases. In the present study, we developed a model of persistent HEV infection in human hepatocytes in which HEV replicates efficiently. This HEV cell culture system is based on differentiated HepaRG cells infected with an isolate of HEV-3 derived from a patient suffering from acute hepatitis E. Efficient replication was maintained for several weeks to several months as well as after seven successive passages on HepaRG naïve cells. Moreover, after six passages onto HepaRG, we found that the virus was still infectious after oral inoculation into pigs. We also showed that ribavirin had an inhibitory effect on HEV replication in HepaRG. In conclusion, this system represents a relevant and efficient in vitro model of HEV replication that could be useful to study HEV biology and identify effective antiviral drugs against chronic HEV infection. Full article

(This article belongs to the Special Issue Hepatitis E Virus Molecular Epidemiology and Evolution)

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14 pages, 1582 KiB

Open AccessArticle

Anti-HEV IgG Avidity Testing: Utility for Diagnosing Acute and Resolved Genotype 3 Infections

by Claudia Minosse, Daniele Lapa, Antonio Coppola, Federica Rapagna, Gianpiero D’Offizi, Chiara Taibi, Raffaella Lionetti, Maria Rosaria Capobianchi, Fiona McPhee and Anna Rosa Garbuglia

Viruses 2021, 13(2), 236; https://doi.org/10.3390/v13020236 - 3 Feb 2021

Cited by 2 | Viewed by 1992

Abstract

European Association of the Study of the Liver (EASL) guidelines specify HEV RNA, as well as anti-HEV IgG and IgM as positive markers for acute HEV infection. HEV RNA assay sensitivity limitations may lead to false negative test results in patients with low levels of viremia. Moreover, anti-HEV IgM positivity is not a reliable indicator for distinguishing between acute and resolved infections given the ability of this antibody to persist several months after a resolved infection. Our study aims were to assess HEV IgG avidity for diagnosing acute and resolved infections, regardless of the anti-HEV IgM serostatus, and examine assay reliability when evaluating different genotype 3 (GT3) HEV subtypes. Patient serum samples (n = 104) were tested for HEV IgG avidity by utilizing the DIA.PRO kit on a DSX automated instrument. Among patients identified with acute HEV infections, 32 were infected with GT3: GT3c (n = 5), GT3e (n = 8), 3f (n = 17) and GT3-unsubtyped (n = 2). Avidity sensitivity was 91.2% and specificity was 100%. For patients with long-lasting anti-HEV IgM persistence, an Avidity Index >70% was observed. Thus, the DIA.PRO avidity assay may be utilized to distinguish between recently acquired and resolved HEV GT3 infections. However, for equivocal results (Avidity Index > 40–70%), HEV RNA molecular testing will be required to confirm a recent infection. Full article

(This article belongs to the Special Issue Hepatitis E Virus Molecular Epidemiology and Evolution)

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6 pages, 217 KiB

Open AccessCommunication

Evidence of Hepatitis E Virus in Goat and Sheep Milk

by Radka Dziedzinska, Miroslava Krzyzankova, Marcel Bena and Petra Vasickova

Viruses 2020, 12(12), 1429; https://doi.org/10.3390/v12121429 - 12 Dec 2020

Cited by 22 | Viewed by 2329

Abstract

Hepatitis E virus (HEV) is the etiological agent behind hepatitis E infection. Domestic pigs and wild boars are the main animal reservoirs of HEV. Very few papers describe HEV infection in goats and sheep. As the data pertaining to the presence of HEV virus in the milk of small ruminants in Europe are lacking, the aim of this paper was to examine a representative number of milk samples from these animals. The detection of HEV genome (HEV RNA) was performed using reverse transcriptase real-time polymerase chain reaction (RT-qPCR). HEV RNA was found in 2.8% of the examined samples. Positivity ranged from 10¹ to 10³ genome equivalents/mL (GE/mL) with a median of 9.99 × 10² GE/mL. On the basis of these results, the milk of small ruminants could represent a source of HEV infection to consumers. Full article

(This article belongs to the Special Issue Hepatitis E Virus Molecular Epidemiology and Evolution)

7 pages, 219 KiB

Open AccessArticle

Seroprevalence of Dromedary Camel HEV in Domestic and Imported Camels from Saudi Arabia

by Sherif Aly El-Kafrawy, Ahmed Mohamed Hassan, Mai Mohamed El-Daly, Ishtiaq Qadri, Ahmed Majdi Tolah, Tagreed Lafi Al-Subhi, Abdulrahman A. Alzahrani, Ghaleb A. Alsaaidi, Nabeela Al-Abdullah, Reham Mohammed Kaki, Tian-Cheng Li and Esam Ibraheem Azhar

Viruses 2020, 12(5), 553; https://doi.org/10.3390/v12050553 - 18 May 2020

Cited by 13 | Viewed by 3541

Abstract

Hepatitis E Virus (HEV) imposes a major health concern in areas with very poor sanitation in Africa and Asia. The pathogen is transmitted mainly through ingesting contaminated water or food, coming into contact with affected people, and blood transfusions. Very few reports including old reports are available on the prevalence of HEV in Saudi Arabia in humans and no reports exist on HEV prevalence in camels. Dromedary camel trade and farming are increasing in Saudi Arabia with importation occurring unidirectionally from Africa to Saudi Arabia. DcHEV transmission to humans has been reported in one case from the United Arab Emeritus (UAE). This instigated us to perform this investigation of the seroprevalence of HEV in imported and domestic camels in Saudi Arabia. Serum samples were collected from imported and domestic camels. DcHEV-Abs were detected in collected sera using ELISA. The prevalence of DcHEV in the collected samples was 23.1% with slightly lower prevalence in imported camels than domestic camels (22.4% vs. 25.4%, p value = 0.3). Gender was significantly associated with the prevalence of HEV in the collected camels (p value = 0.015) where males (31.6%) were more infected than females (13.4%). This study is the first study to investigate the prevalence of HEV in dromedary camels from Saudi Arabia. The high seroprevalence of DcHEV in dromedaries might indicate their role as a zoonotic reservoir for viral infection to humans. Future HEV seroprevalence studies in humans are needed to investigate the role of DcHEV in the Saudi human population. Full article

(This article belongs to the Special Issue Hepatitis E Virus Molecular Epidemiology and Evolution)

Review

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23 pages, 1333 KiB

Open AccessReview

Advances in Hepatitis E Virus Biology and Pathogenesis

by Shaoli Lin and Yan-Jin Zhang

Viruses 2021, 13(2), 267; https://doi.org/10.3390/v13020267 - 9 Feb 2021

Cited by 15 | Viewed by 4475

Abstract

Hepatitis E virus (HEV) is one of the causative agents for liver inflammation across the world. HEV is a positive-sense single-stranded RNA virus. Human HEV strains mainly belong to four major genotypes in the genus Orthohepevirus A, family Hepeviridae. Among the four genotypes, genotype 1 and 2 are obligate human pathogens, and genotype 3 and 4 cause zoonotic infections. HEV infection with genotype 1 and 2 mainly presents as acute and self-limiting hepatitis in young adults. However, HEV infection of pregnant women with genotype 1 strains can be exacerbated to fulminant hepatitis, resulting in a high rate of case fatality. As pregnant women maintain the balance of maternal-fetal tolerance and effective immunity against invading pathogens, HEV infection with genotype 1 might dysregulate the balance and cause the adverse outcome. Furthermore, HEV infection with genotype 3 can be chronic in immunocompromised patients, with rapid progression, which has been a challenge since it was reported years ago. The virus has a complex interaction with the host cells in downregulating antiviral factors and recruiting elements to generate a conducive environment of replication. The virus-cell interactions at an early stage might determine the consequence of the infection. In this review, advances in HEV virology, viral life cycle, viral interference with the immune response, and the pathogenesis in pregnant women are discussed, and perspectives on these aspects are presented. Full article

(This article belongs to the Special Issue Hepatitis E Virus Molecular Epidemiology and Evolution)

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17 pages, 2509 KiB

Open AccessReview

Review of Hepatitis E Virus in Rats: Evident Risk of Species Orthohepevirus C to Human Zoonotic Infection and Disease

by Gábor Reuter, Ákos Boros and Péter Pankovics

Viruses 2020, 12(10), 1148; https://doi.org/10.3390/v12101148 - 9 Oct 2020

Cited by 44 | Viewed by 3770

Abstract

Hepatitis E virus (HEV) (family Hepeviridae) is one of the most common human pathogens, causing acute hepatitis and an increasingly recognized etiological agent in chronic hepatitis and extrahepatic manifestations. Recent studies reported that not only are the classical members of the species Orthohepevirus A (HEV-A) pathogenic to humans but a genetically highly divergent rat origin hepevirus (HEV-C1) in species Orthohepevirus C (HEV-C) is also able to cause zoonotic infection and symptomatic disease (hepatitis) in humans. This review summarizes the current knowledge of hepeviruses in rodents with special focus of rat origin HEV-C1. Cross-species transmission and genetic diversity of HEV-C1 and confirmation of HEV-C1 infections and symptomatic disease in humans re-opened the long-lasting and full of surprises story of HEV in human. This novel knowledge has a consequence to the epidemiology, clinical aspects, laboratory diagnosis, and prevention of HEV infection in humans. Full article

(This article belongs to the Special Issue Hepatitis E Virus Molecular Epidemiology and Evolution)

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