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Hepatitis E Virus
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Hepatitis E Virus

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

Deadline for manuscript submissions: closed (30 April 2019) | Viewed by 79887

Special Issue Editor

Prof. Dr. Alexander Ploss

grade E-Mail Website
Guest Editor
Department of Molecular Biology, Princeton University, 119 Lewis Thomas Laboratory Washington Road, Princeton, NJ 08544-1014, USA
Interests: HBV; HCV; HEV; HDV; flaviviruses; animal models; viral hepatitis

Special Issue Information

Dear Colleagues,

Infections with hepatitis E virus (HEV), a member of the hepeviridae, remain a major medical concern in developing countries but have also emerged as a health threat in specific patient populations in industrialized countries. HEV causes a broad range of clinical manifestations and disease severities, which remain incompletely understood. In contrast to the other human hepatitis viruses, HEV is found in an ever-increasing range of species, which raises interesting questions about the restrictions—or the lack thereof—of the zoonotic reservoir. Although a vaccine for HEV has been developed, it is only licensed in China. Additionally, no effective, non-teratogenic, or specific treatments against HEV infections are currently available. Although progress has been made in characterizing HEV biology, the scarcity of adequate experimental platforms has previously hampered research. With the advent of new model systems, a clearer picture of the mechanistic details of the HEV life-cycle starts to emerge, along with how this virus interacts with its different hosts.

This Special Issue is designed to provide an up-to-date view of HEV biology, including the molecular biology of the virus, virus–host interactions, and the development of new therapies.

Prof. Dr. Alexander Ploss
Guest Editor

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Published Papers (16 papers)

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Research

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13 pages, 1208 KiB  
Article
Plasma Hepatitis E Virus Kinetics in Solid Organ Transplant Patients Receiving Ribavirin
by Sebastien Lhomme, Swati DebRoy, Nassim Kamar, Florence Abravanel, David Metsu, Olivier Marion, Chloé Dimeglio, Scott J. Cotler, Jacques Izopet and Harel Dahari
Viruses 2019, 11(7), 630; https://0-doi-org.brum.beds.ac.uk/10.3390/v11070630 - 09 Jul 2019
Cited by 8 | Viewed by 2988
Abstract
Hepatitis E virus (HEV) infection causes chronic hepatitis in solid organ transplant (SOT) recipients. Antiviral therapy consists of three months of ribavirin, although response rates are not optimal. We characterized plasma HEV kinetic patterns in 41 SOT patients during ribavirin therapy. After a [...] Read more.
Hepatitis E virus (HEV) infection causes chronic hepatitis in solid organ transplant (SOT) recipients. Antiviral therapy consists of three months of ribavirin, although response rates are not optimal. We characterized plasma HEV kinetic patterns in 41 SOT patients during ribavirin therapy. After a median pharmacological delay of three (range: 0–21) days, plasma HEV declined from a median baseline level of 6.12 (3.53–7.45) log copies/mL in four viral kinetic patterns: (i) monophasic (n = 18), (ii) biphasic (n = 13), (iii) triphasic (n = 8), and (iv) flat-partial response (n = 2). The mean plasma HEV half-life was estimated to be 2.0 ± 0.96 days. Twenty-five patients (61%) had a sustained virological response (SVR) 24 weeks after completion of therapy. Viral kinetic patterns (i)–(iii) were not associated with baseline characteristics or outcome of therapy. A flat-partial response was associated with treatment failure. All patients with a log concentration decrease of plasma HEV at day seven of >15% from baseline achieved SVR. In conclusion, viral kinetic modeling of plasma HEV under ribavirin therapy showed, for the first time, four distinct kinetic profiles, a median pharmacologic delay of three days, and an estimated HEV half-life of two days. Viral kinetic patterns were not associated with response to therapy, with the exception of a flat-partial response. Full article
(This article belongs to the Special Issue Hepatitis E Virus)
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10 pages, 716 KiB  
Article
Hepatitis E and Allogeneic Hematopoietic Stem Cell Transplantation: A French Nationwide SFGM-TC Retrospective Study
by Aliénor Xhaard, Anne-Marie Roque-Afonso, Vincent Mallet, Patricia Ribaud, Stéphanie Nguyen-Quoc, Pierre-Simon Rohrlich, Reza Tabrizi, Johanna Konopacki, Séverine Lissandre, Florence Abravanel, Régis Peffault de Latour and Anne Huynh
Viruses 2019, 11(7), 622; https://0-doi-org.brum.beds.ac.uk/10.3390/v11070622 - 05 Jul 2019
Cited by 10 | Viewed by 2409
Abstract
Usually self-limited, hepatitis E virus (HEV) infection may evolve to chronicity and cirrhosis in immunosuppressed patients. HEV infection has been described in solid-organ transplantation and hematology patients, but for allogeneic hematopoietic stem cell transplant (alloHSCT) recipients, only small cohorts are available. This retrospective [...] Read more.
Usually self-limited, hepatitis E virus (HEV) infection may evolve to chronicity and cirrhosis in immunosuppressed patients. HEV infection has been described in solid-organ transplantation and hematology patients, but for allogeneic hematopoietic stem cell transplant (alloHSCT) recipients, only small cohorts are available. This retrospective nationwide multi-center series aimed to describe HEV diagnostic practices in alloHSCT French centers, and the course of infection in the context of alloHSCT. Twenty-nine out of 37 centers participated. HEV search in case of liver function tests (LFT) abnormalities was never performed in 24% of centers, occasionally in 55%, and systematically in 21%. Twenty-five cases of active HEV infection were diagnosed in seven centers, all because of LFT abnormalities, by blood nucleic acid testing. HEV infection was diagnosed in three patients before alloHSCT; HEV infection did not influence transplantation planning, and resolved spontaneously before or after alloHSCT. Twenty-two patients were diagnosed a median of 283 days after alloHSCT. Nine patients (41%) had spontaneous viral clearance, mostly after immunosuppressive treatment decrease. Thirteen patients (59%) received ribavirin, with sustained viral clearance in 11/12 evaluable patients. We observed three HEV recurrences but no HEV-related death or liver failure, nor evolution to cirrhosis. Full article
(This article belongs to the Special Issue Hepatitis E Virus)
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9 pages, 1546 KiB  
Article
Hepatitis E Virus Infections among Patients with Acute Febrile Jaundice in Burkina Faso
by Chloé Dimeglio, Dramane Kania, Judith Mbombi Mantono, Thérèse Kagoné, Sylvie Zida, Souleymane Tassembedo, Amadou Dicko, Bachirou Tinto, Seydou Yaro, Hervé Hien, Jérémi Rouamba, Brice Bicaba, Isaïe Medah, Nicolas Meda, Oumar Traoré, Edouard Tuaillon, Florence Abravanel and Jacques Izopet
Viruses 2019, 11(6), 554; https://0-doi-org.brum.beds.ac.uk/10.3390/v11060554 - 14 Jun 2019
Cited by 7 | Viewed by 3439
Abstract
Hepatitis E virus infection is a significant public health problem in many parts of the world including Africa. We tested serum samples from 900 patients in Burkina Faso presenting with febrile icterus. They all tested negative for yellow fever, but those from 23/900 [...] Read more.
Hepatitis E virus infection is a significant public health problem in many parts of the world including Africa. We tested serum samples from 900 patients in Burkina Faso presenting with febrile icterus. They all tested negative for yellow fever, but those from 23/900 (2.6%) patients contained markers of acute HEV infection (anti-HEV IgM and HEV RNA positive). Genotyping indicated that 14 of the strains were HEV genotype 2b. There was an overall HEV IgG seroprevalence of 18.2% (164/900). In a bivariate analysis, the factors linked to HEV exposure were climate and patient age. Older patients and those living in arid regions were more likely to have HEV infection. HEV genotype 2b circulating only in humans can be involved in some acute febrile icterus cases in Burkina Faso. Better access to safe water, sanitation, and improved personal hygiene should improve control of HEV infection in this country. Full article
(This article belongs to the Special Issue Hepatitis E Virus)
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17 pages, 2171 KiB  
Article
Isolation of Subtype 3c, 3e and 3f-Like Hepatitis E Virus Strains Stably Replicating to High Viral Loads in an Optimized Cell Culture System
by Mathias Schemmerer, Reimar Johne, Monika Erl, Wolfgang Jilg and Jürgen J. Wenzel
Viruses 2019, 11(6), 483; https://0-doi-org.brum.beds.ac.uk/10.3390/v11060483 - 28 May 2019
Cited by 35 | Viewed by 4158
Abstract
The hepatitis E virus (HEV) is transmitted via the faecal–oral route in developing countries (genotypes 1 and 2) or through contaminated food and blood products worldwide (genotypes 3 and 4). In Europe, HEV subtypes 3c, 3e and 3f are predominant. HEV is the [...] Read more.
The hepatitis E virus (HEV) is transmitted via the faecal–oral route in developing countries (genotypes 1 and 2) or through contaminated food and blood products worldwide (genotypes 3 and 4). In Europe, HEV subtypes 3c, 3e and 3f are predominant. HEV is the leading cause of acute hepatitis globally and immunocompromised patients are particularly at risk. Because of a lack of cell culture systems efficiently propagating wild-type viruses, research on HEV is mostly based on cell culture-adapted isolates carrying uncommon insertions in the hypervariable region (HVR). While optimizing the cell culture system using the cell culture-adapted HEV strain 47832c, we isolated three wild-type strains derived from clinical specimens representing the predominant spectrum of HEV in Europe. The novel isolates 14-16753 (3c), 14-22707 (3e) and 15-22016 (3f-like) replicate to high viral loads of 108, 109 and 106.5 HEV RNA copies/mL at 14 days post-inoculation, respectively. In addition, they could be kept as persistently infected cell cultures with constant high viral loads (~109 copies/mL) for more than a year. In contrast to the latest isolates 47832c, LBPR-0379 and Kernow-C1, the new isolates do not carry genome insertions in the HVR. Optimization of HEV cell culture identified amphotericin B, distinct salts and fetal calf serum (FCS) as important medium supplements. Overconfluent cell layers increased infectivity and virus production. PLC/PRF/5, HuH-7-Lunet BLR, A549 and HepG2/C3A supported replication with different efficiencies. The novel strains and optimized cell culture system may be useful for studies on the HEV life cycle, inactivation, specific drug and vaccine development. Full article
(This article belongs to the Special Issue Hepatitis E Virus)
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10 pages, 393 KiB  
Article
Chronic Hepatitis E in Rheumatology and Internal Medicine Patients: A Retrospective Multicenter European Cohort Study
by Sven Pischke, Jean-Marie Peron, Moritz von Wulffen, Johann von Felden, Christoph Höner zu Siederdissen, Sophie Fournier, Marc Lütgehetmann, Christoph Iking-Konert, Dominik Bettinger, Gabriella Par, Robert Thimme, Alain Cantagrel, Ansgar W. Lohse, Heiner Wedemeyer, Robert de Man and Vincent Mallet
Viruses 2019, 11(2), 186; https://0-doi-org.brum.beds.ac.uk/10.3390/v11020186 - 22 Feb 2019
Cited by 32 | Viewed by 4033
Abstract
Objectives: Hepatitis E virus (HEV) infection is a pandemic with regional outbreaks, including in industrialized countries. HEV infection is usually self-limiting but can progress to chronic hepatitis E in transplant recipients and HIV-infected patients. Whether other immunocompromised hosts, including rheumatology and internal medicine [...] Read more.
Objectives: Hepatitis E virus (HEV) infection is a pandemic with regional outbreaks, including in industrialized countries. HEV infection is usually self-limiting but can progress to chronic hepatitis E in transplant recipients and HIV-infected patients. Whether other immunocompromised hosts, including rheumatology and internal medicine patients, are at risk of developing chronic HEV infection is unclear. Methods: We conducted a retrospective European multicenter cohort study involving 21 rheumatology and internal medicine patients with HEV infection between April 2014 and April 2016. The underlying diseases included rheumatoid arthritis (n = 5), psoriatic arthritis (n = 4), other variants of chronic arthritis (n = 4), primary immunodeficiency (n = 3), systemic granulomatosis (n = 2), lupus erythematosus (n = 1), Erdheim–Chester disease (n = 1), and retroperitoneal fibrosis (n = 1). Results: HEV infection lasting longer than 3 months was observed in seven (33%) patients, including two (40%) patients with rheumatoid arthritis, three (100%) patients with primary immunodeficiency, one (100%) patient with retroperitoneal fibrosis and one (100%) patient with systemic granulomatosis. Patients with HEV infection lasting longer than 3 months were treated with methotrexate without corticosteroids (n = 2), mycophenolate mofetil/prednisone (n = 1), and sirolimus/prednisone (n = 1). Overall, 8/21 (38%) and 11/21 (52%) patients cleared HEV with and without ribavirin treatment, respectively. One patient experienced an HEV relapse after initially successful ribavirin therapy. One patient (5%) was lost to follow-up, and no patients died from hepatic complications. Conclusion: Rheumatology and internal medicine patients, including patients treated with methotrexate without corticosteroids, are at risk of developing chronic HEV infection. Rheumatology and internal medicine patients with abnormal liver tests should be screened for HEV infection. Full article
(This article belongs to the Special Issue Hepatitis E Virus)
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Review

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10 pages, 738 KiB  
Review
Hepatitis E Virus Entry
by Xin Yin and Zongdi Feng
Viruses 2019, 11(10), 883; https://0-doi-org.brum.beds.ac.uk/10.3390/v11100883 - 20 Sep 2019
Cited by 27 | Viewed by 7228
Abstract
Hepatitis E virus (HEV) infection is a major cause of acute hepatitis worldwide. It is transmitted enterically but replicates in the liver. Recent studies indicate that HEV exists in two forms: naked, nonenveloped virions that are shed into feces to mediate inter-host transmission, [...] Read more.
Hepatitis E virus (HEV) infection is a major cause of acute hepatitis worldwide. It is transmitted enterically but replicates in the liver. Recent studies indicate that HEV exists in two forms: naked, nonenveloped virions that are shed into feces to mediate inter-host transmission, and membrane-cloaked, quasienveloped virions that circulate in the bloodstream to mediate virus spread within a host. Both virion types are infectious, but differ in the way they infect cells. Elucidating the entry mechanism for both virion types is essential to understand HEV biology and pathogenesis, and is relevant to the development of treatments and preventions for HEV. This review summarizes the current understanding of the cell entry mechanism for these two HEV virion types. Full article
(This article belongs to the Special Issue Hepatitis E Virus)
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17 pages, 798 KiB  
Review
Hepatitis E Virus Replication
by Robert LeDesma, Ila Nimgaonkar and Alexander Ploss
Viruses 2019, 11(8), 719; https://0-doi-org.brum.beds.ac.uk/10.3390/v11080719 - 06 Aug 2019
Cited by 34 | Viewed by 6528
Abstract
Hepatitis E virus (HEV) is a small quasi-enveloped, (+)-sense, single-stranded RNA virus belonging to the Hepeviridae family. There are at least 20 million HEV infections annually and 60,000 HEV-related deaths worldwide. HEV can cause up to 30% mortality in pregnant women and progress [...] Read more.
Hepatitis E virus (HEV) is a small quasi-enveloped, (+)-sense, single-stranded RNA virus belonging to the Hepeviridae family. There are at least 20 million HEV infections annually and 60,000 HEV-related deaths worldwide. HEV can cause up to 30% mortality in pregnant women and progress to liver cirrhosis in immunocompromised individuals and is, therefore, a greatly underestimated public health concern. Although a prophylactic vaccine for HEV has been developed, it is only licensed in China, and there is currently no effective, non-teratogenic treatment. HEV encodes three open reading frames (ORFs). ORF1 is the largest viral gene product, encoding the replicative machinery of the virus including a methyltransferase, RNA helicase, and an RNA-dependent RNA polymerase. ORF1 additionally contains a number of poorly understood domains including a hypervariable region, a putative protease, and the so-called ‘X’ and ‘Y’ domains. ORF2 is the viral capsid essential for formation of infectious particles and ORF3 is a small protein essential for viral release. In this review, we focus on the domains encoded by ORF1, which collectively mediate the virus’ asymmetric genome replication strategy. We summarize what is known, unknown, and hotly debated regarding the coding and non-coding regions of HEV ORF1, and present a model of how HEV replicates its genome. Full article
(This article belongs to the Special Issue Hepatitis E Virus)
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19 pages, 1034 KiB  
Review
The Clinical Perspective on Hepatitis E
by Thomas Horvatits, Julian Schulze zur Wiesch, Marc Lütgehetmann, Ansgar W. Lohse and Sven Pischke
Viruses 2019, 11(7), 617; https://0-doi-org.brum.beds.ac.uk/10.3390/v11070617 - 05 Jul 2019
Cited by 73 | Viewed by 6449
Abstract
Every year, there are an estimated 20 million hepatitis E virus (HEV) infections worldwide, leading to an estimated 3.3 million symptomatic cases of hepatitis E. HEV is largely circulating in the west and is associated with several hepatic and extrahepatic diseases. HEV Genotype [...] Read more.
Every year, there are an estimated 20 million hepatitis E virus (HEV) infections worldwide, leading to an estimated 3.3 million symptomatic cases of hepatitis E. HEV is largely circulating in the west and is associated with several hepatic and extrahepatic diseases. HEV Genotype 1 and 2 infections are waterborne and causative for epidemics in the tropics, while genotype 3 and 4 infections are zoonotic diseases and are mainly transmitted by ingestion of undercooked pork in industrialized nations. The clinical course of these infections differs: genotype 1 and 2 infection can cause acute illness and can lead to acute liver failure (ALF) or acute on chronic liver failure (ACLF) with a high mortality rate of 20% in pregnant women. In contrast, the majority of HEV GT-3 and -4 infections have a clinically asymptomatic course and only rarely lead to acute on chronic liver failure in elderly or patients with underlying liver disease. Immunosuppressed individuals infected with genotype 3 or 4 may develop chronic hepatitis E, which then can lead to life-threatening cirrhosis. Furthermore, several extra-hepatic manifestations affecting various organs have been associated with ongoing or previous HEV infections but the causal link for many of them still needs to be proven. There is no approved specific therapy for the treatment of acute or chronic HEV GT-3 or -4 infections but off-label use of ribavirin has been demonstrated to be safe and effective in the majority of patients. However, in approximately 15% of chronically HEV infected patients, cure is not possible. Full article
(This article belongs to the Special Issue Hepatitis E Virus)
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22 pages, 1248 KiB  
Review
Cell Culture Models for Hepatitis E Virus
by Rebecca Menhua Fu, Charlotte Caroline Decker and Viet Loan Dao Thi
Viruses 2019, 11(7), 608; https://0-doi-org.brum.beds.ac.uk/10.3390/v11070608 - 03 Jul 2019
Cited by 32 | Viewed by 6092
Abstract
Despite a growing awareness, hepatitis E virus (HEV) remains understudied and investigations have been historically hampered by the absence of efficient cell culture systems. As a result, the pathogenesis of HEV infection and basic steps of the HEV life cycle are poorly understood. [...] Read more.
Despite a growing awareness, hepatitis E virus (HEV) remains understudied and investigations have been historically hampered by the absence of efficient cell culture systems. As a result, the pathogenesis of HEV infection and basic steps of the HEV life cycle are poorly understood. Major efforts have recently been made through the development of HEV infectious clones and cellular systems that significantly advanced HEV research. Here, we summarize these systems, discussing their advantages and disadvantages for HEV studies. We further capitalize on the need for HEV-permissive polarized cell models to better recapitulate the entire HEV life cycle and transmission. Full article
(This article belongs to the Special Issue Hepatitis E Virus)
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20 pages, 564 KiB  
Review
Animal Models for Hepatitis E Virus
by Laura Corneillie, Dominic H. Banda and Philip Meuleman
Viruses 2019, 11(6), 564; https://0-doi-org.brum.beds.ac.uk/10.3390/v11060564 - 18 Jun 2019
Cited by 19 | Viewed by 6531
Abstract
Hepatitis E virus (HEV) is an underdiagnosed pathogen with approximately 20 million infections each year and currently the most common cause of acute viral hepatitis. HEV was long considered to be confined to developing countries but there is increasing evidence that it is [...] Read more.
Hepatitis E virus (HEV) is an underdiagnosed pathogen with approximately 20 million infections each year and currently the most common cause of acute viral hepatitis. HEV was long considered to be confined to developing countries but there is increasing evidence that it is also a medical problem in the Western world. HEV that infects humans belongs to the Orthohepevirus A species of the Hepeviridae family. Novel HEV-like viruses have been observed in a variety of animals and some have been shown to be able to cross the species barrier, causing infection in humans. Several cell culture models for HEV have been established in the past years, but their efficiency is usually relatively low. With the circulation of this virus and related viruses in a variety of species, several different animal models have been developed. In this review, we give an overview of these animal models, indicate their main characteristics, and highlight how they may contribute to our understanding of the basic aspects of the viral life cycle and cross-species infection, the study of pathogenesis, and the evaluation of novel preventative and therapeutic strategies. Full article
(This article belongs to the Special Issue Hepatitis E Virus)
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12 pages, 1075 KiB  
Review
The Interplay between Host Innate Immunity and Hepatitis E Virus
by Yang Li, Changbo Qu, Peifa Yu, Xumin Ou, Qiuwei Pan and Wenshi Wang
Viruses 2019, 11(6), 541; https://0-doi-org.brum.beds.ac.uk/10.3390/v11060541 - 11 Jun 2019
Cited by 18 | Viewed by 4527
Abstract
Hepatitis E virus (HEV) infection represents an emerging global health issue, whereas the clinical outcomes vary dramatically among different populations. The host innate immune system provides a first-line defense against the infection, but dysregulation may partially contribute to severe pathogenesis. A growing body [...] Read more.
Hepatitis E virus (HEV) infection represents an emerging global health issue, whereas the clinical outcomes vary dramatically among different populations. The host innate immune system provides a first-line defense against the infection, but dysregulation may partially contribute to severe pathogenesis. A growing body of evidence has indicated the active response of the host innate immunity to HEV infection both in experimental models and in patients. In turn, HEV has developed sophisticated strategies to counteract the host immune system. In this review, we aim to comprehensively decipher the processes of pathogen recognition, interferon, and inflammatory responses, and the involvement of innate immune cells in HEV infection. We further discuss their implications in understanding the pathogenic mechanisms and developing antiviral therapies. Full article
(This article belongs to the Special Issue Hepatitis E Virus)
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13 pages, 988 KiB  
Review
Hepatitis E Virus Assembly and Release
by Xiaohui Ju and Qiang Ding
Viruses 2019, 11(6), 539; https://0-doi-org.brum.beds.ac.uk/10.3390/v11060539 - 09 Jun 2019
Cited by 18 | Viewed by 4662
Abstract
Hepatitis E is an underestimated threat to public health, caused by the hepatitis E virus (HEV). HEV is the most common cause of acute viral hepatitis in the world, with no available direct-acting antiviral treatment. According to a recent WHO report, 20 million [...] Read more.
Hepatitis E is an underestimated threat to public health, caused by the hepatitis E virus (HEV). HEV is the most common cause of acute viral hepatitis in the world, with no available direct-acting antiviral treatment. According to a recent WHO report, 20 million people become infected with HEV annually, resulting in 44,000 deaths. However, due to the scarcity of efficient in vitro cell culture systems for HEV, our knowledge of the life cycle of HEV is incomplete. Recently, significant progress has been made towards gaining a more comprehensive view of the HEV life cycle, as several in vitro culturing systems have been developed in recent years. Here, we review current knowledge and recent advances with regard to the HEV life cycle, with a particular focus on the assembly and release of viral particles. We also discuss the knowledge gaps in HEV assembly and release. Meanwhile, we highlight experimental platforms that could potentially be utilized to fill these gaps. Lastly, we offer perspectives on the future of research into HEV virology and its interaction with host cells. Full article
(This article belongs to the Special Issue Hepatitis E Virus)
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16 pages, 2631 KiB  
Review
Hepatitis E Virus Drug Development
by Volker Kinast, Thomas L Burkard, Daniel Todt and Eike Steinmann
Viruses 2019, 11(6), 485; https://0-doi-org.brum.beds.ac.uk/10.3390/v11060485 - 28 May 2019
Cited by 39 | Viewed by 5177
Abstract
Hepatitis E virus (HEV) is an underestimated disease, leading to estimated 20 million infections and up to 70,000 deaths annually. Infections are mostly asymptomatic but can reach mortality rates up to 25% in pregnant women or become chronic in immunocompromised patients. The current [...] Read more.
Hepatitis E virus (HEV) is an underestimated disease, leading to estimated 20 million infections and up to 70,000 deaths annually. Infections are mostly asymptomatic but can reach mortality rates up to 25% in pregnant women or become chronic in immunocompromised patients. The current therapy options are limited to the unspecific antivirals Ribavirin (RBV) and pegylated Interferon-α (pegIFN-α). RBV leads to viral clearance in only 80% of patients treated, and is, similar to pegIFN-α, contraindicated in the major risk group of pregnant women, emphasizing the importance of new therapy options. In this review, we focus on the urgent need and current efforts in HEV drug development. We provide an overview of the current status of HEV antiviral research. Furthermore, we discuss strategies for drug development and the limitations of the approaches with respect to HEV. Full article
(This article belongs to the Special Issue Hepatitis E Virus)
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28 pages, 1325 KiB  
Review
Genetic Variability and Evolution of Hepatitis E Virus
by Putu Prathiwi Primadharsini, Shigeo Nagashima and Hiroaki Okamoto
Viruses 2019, 11(5), 456; https://0-doi-org.brum.beds.ac.uk/10.3390/v11050456 - 18 May 2019
Cited by 71 | Viewed by 5410
Abstract
Hepatitis E virus (HEV) is a single-stranded positive-sense RNA virus. HEV can cause both acute and chronic hepatitis, with the latter usually occurring in immunocompromised patients. Modes of transmission range from the classic fecal–oral route or zoonotic route, to relatively recently recognized but [...] Read more.
Hepatitis E virus (HEV) is a single-stranded positive-sense RNA virus. HEV can cause both acute and chronic hepatitis, with the latter usually occurring in immunocompromised patients. Modes of transmission range from the classic fecal–oral route or zoonotic route, to relatively recently recognized but increasingly common routes, such as via the transfusion of blood products or organ transplantation. Extrahepatic manifestations, such as neurological, kidney and hematological abnormalities, have been documented in some limited cases, typically in patients with immune suppression. HEV has demonstrated extensive genomic diversity and a variety of HEV strains have been identified worldwide from human populations as well as growing numbers of animal species. The genetic variability and constant evolution of HEV contribute to its physiopathogenesis and adaptation to new hosts. This review describes the recent classification of the Hepeviridae family, global genotype distribution, clinical significance of HEV genotype and genomic variability and evolution of HEV. Full article
(This article belongs to the Special Issue Hepatitis E Virus)
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21 pages, 302 KiB  
Review
The Current Host Range of Hepatitis E Viruses
by Scott P Kenney
Viruses 2019, 11(5), 452; https://0-doi-org.brum.beds.ac.uk/10.3390/v11050452 - 17 May 2019
Cited by 71 | Viewed by 4788
Abstract
Hepatitis E virus (HEV) is an emerging zoonotic pathogen transmitting both human to human via the fecal oral route and from animals to humans through feces, direct contact, and consumption of contaminated meat products. Understanding the host range of the virus is critical [...] Read more.
Hepatitis E virus (HEV) is an emerging zoonotic pathogen transmitting both human to human via the fecal oral route and from animals to humans through feces, direct contact, and consumption of contaminated meat products. Understanding the host range of the virus is critical for determining where potential threats to human health may be emerging from and where potential reservoirs for viral persistence in the environment may be hiding. Initially thought to be a human specific disease endemic to developing countries, the identification of swine as a primary host for genotypes 3 and 4 HEV in industrialized countries has begun a long journey of discovering novel strains of HEV and their animal hosts. As we continue identifying new strains of HEV in disparate animal species, it is becoming abundantly clear that HEV has a broad host range and many of these HEV strains can cross between differing animal species. These cross-species transmitting strains pose many unique challenges to human health as they are often unrecognized as sources of viral transmission. Full article
(This article belongs to the Special Issue Hepatitis E Virus)
16 pages, 1438 KiB  
Review
Meta-Analysis of Human IgG anti-HEV Seroprevalence in Industrialized Countries and a Review of Literature
by Lisandru Capai, Alessandra Falchi and Rémi Charrel
Viruses 2019, 11(1), 84; https://0-doi-org.brum.beds.ac.uk/10.3390/v11010084 - 20 Jan 2019
Cited by 34 | Viewed by 4526
Abstract
Although Hepatitis E is increasingly described as a major cause of liver disease in industrialized countries, the epidemiology is far from being fully elucidated. We provide here a comprehensive review of documented clusters of cases, and of serological studies conducted in populations with [...] Read more.
Although Hepatitis E is increasingly described as a major cause of liver disease in industrialized countries, the epidemiology is far from being fully elucidated. We provide here a comprehensive review of documented clusters of cases, and of serological studies conducted in populations with distinct types of exposure. Seroprevalence rates range from <5% to >50% depending on the countries and the groups of population. Such discrepancies can be attributed to the type of serological assay used, but this solves only a part of the problem. We performed a meta-analysis of studies performed with the broadly used Wantai HEV-IgG ELISA and found striking differences that remain difficult to understand with the current knowledge of transmission pathways. Full article
(This article belongs to the Special Issue Hepatitis E Virus)
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