Hepatitis E Virus Mutations: Functional and Clinical Relevance

Tong, Hoang Van; Hoàn, Nghiêm Xuân; Wang, Bo; Wedemeyer, Heiner; Bock, C.‐Thomas; Velavan, Thirumalaisamy P.

doi:10.1016/j.ebiom.2016.07.039

Cited by 60 publications

(60 citation statements)

References 117 publications

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“…41 HEV genome is composed of a set of 3 overlapping open reading frames (ORFs), 5′-untranslated and 3′-untranslated regions (UTRs), and 2 essential cis-reactive elements (CRE), which are all essential for HEV replication. 61 HEV has 4 main established genotypes(1 to 4) that are globally distributed into different epidemiological patterns based on socioeconomic factors and ecology ( Figure 2). 62 Generally, genotype 1 (HEV-1) accounts for epidemics in parts of Asia, while genotype 2 (HEV-2) is more prevalent in Africa, Mexico, and other developing countries.…”

Section: Molecular Epidemiology Of Hev Genotypesmentioning

confidence: 99%

Seroprevalence and incidence of hepatitis E virus among blood donors: A review

2017

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Hepatitis E virus (HEV) is an RNA virus with 4 main genotypes. HEV-1 and HEV-2 infect solely humans, while HEV-3 and HEV-4 infect humans and various animals such as pigs, deer, and rabbits. HEV-5 and HEV-6 infect mainly wild boar. Recently, new genotypes, known as HEV-7 and HEV-8, were found to infect camels and humans. HEV is globally distributed into different epidemiological patterns based on socioeconomic factors and ecology. Although HEV is mainly transmitted through the fecal-oral route, it was also recognized as a transfusion-transmitted virus. Transmission through blood donation was documented worldwide with rising annual observations, accounting for more than 2.5% of all transmissions. HEV infection is usually asymptomatic or subclinical in immunocompetent individuals, so it remains questionable whether there is an urgent need to screen for HEV prior to blood transfusion. Moreover, recent studies conducted in the Middle East and North Africa (MENA) region indicate that HEV is highly endemic. Here, we provide a review on HEV epidemiology, transmission, and laboratory diagnosis, giving special emphasis to the newly discovered genotypes, HEV-7 and HEV-8. Furthermore, we underscore the findings of recent HEV seroprevalence and viremia studies among blood donors worldwide. We also shed light on similar studies performed among blood donors in the MENA region.

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Section: Molecular Epidemiology Of Hev Genotypesmentioning

confidence: 99%

Seroprevalence and incidence of hepatitis E virus among blood donors: A review

2017

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“…HEV is a nonenveloped virus with an approximately 7.2-kb positive-sense, singlestranded RNA genome that consists of three open reading frames (ORF1, ORF2, and ORF3), 5= and 3= untranslated regions (UTRs), and a poly(A) tract at the 3= end. ORF1 encodes the nonstructural proteins; ORF2 expresses the capsid protein; and ORF3 partially overlaps ORF2 and encodes a multifunctional phosphoprotein (16,17). The latest consensus proposals for HEV classification by the International Committee on Taxonomy of Viruses (ICTV) have divided the family Hepeviridae into two genera, Orthohepevirus and Piscihepevirus.…”

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confidence: 99%

Comprehensive Molecular Approach for Characterization of Hepatitis E Virus Genotype 3 Variants

et al. 2018

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Autochthonous hepatitis E virus genotype 3 (HEV-3) infections in industrialized countries are more frequent than previously assumed. HEV-3 is zoonotic and the causal pathogen of chronic hepatitis E. According to the latest classification of the family , 10 designated HEV-3 subtypes (HEV-3a to HEV-3j) and 7 unassigned HEV-3 subtypes are proposed. In order to identify and characterize the HEV-3 variants in circulation, we developed a molecular approach combining a sensitive HEV-specific real-time reverse transcription-PCR (RT-PCR) targeting the overlapping region of HEV ORF2 and ORF3 (the ORF2/3 region) and two newly designed consensus nested RT-PCRs targeting the HEV ORF1 and ORF2 genes, respectively. Since complete genome sequences are required for new HEV-3 subtype assignment, we implemented a straightforward approach for full-length HEV-3 genome amplification. Twenty-nine human serum samples and six human feces samples from chronic hepatitis E patients were selected for evaluation of the system. Viral loads ranged from 1 × 10 to 1.9 × 10 copies/ml of serum and from 1.8 × 10 to 1 × 10 copies/g of feces. Sequence and phylogenetic analyses of partial ORF1 and ORF2 sequences showed that HEV strains had considerable genetic diversity and clustered into the HEV-3c (29/35), HEV-3e (2/35), HEV-3f (2/35), and unassigned HEV-3 (2/35) subtypes. Moreover, from these strains, three full-length HEV-3 genome sequences were generated and characterized. DE/15-0030 represents a typical HEV-3c strain (95.7% nucleotide identity to wbGER27), while DE/15-0031 and SW/16-0282 have <89.2% homology to known HEV-3 strains and are phylogenetically divergent, indicating novel HEV-3 subtypes. In summary, our approach will significantly facilitate the detection, quantification, and determination of HEV-3 strains and will thus help to improve molecular diagnostics and our knowledge of HEV diversity and evolution.

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“…However, it is unknown whether this vaccine provide protection against genotype 3 virus strains and patients at risk for chronic HEV [11]. In addition, antiviral treatment in immunocompromised patients might induce mutations in ORF2 gene, that could lead to the emergence of HEV vaccine escape mutants, as it has been reported for HBV [28][29][30].…”

Section: Introductionmentioning

confidence: 95%

Phage-displayed peptides that mimic epitopes of hepatitis E virus capsid

Larralde

Petrík

2017

Med Microbiol Immunol

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Hepatitis E is an emerging zoonotic infection of increasing public health threat for the UK, especially for immunosuppressed individuals. A human recombinant vaccine has been licensed only in China and is not clear whether it protects against hepatitis E virus (HEV) genotype 3, the most prevalent in Europe. The aim of this study was to use phage display technology as a tool to identify peptides that mimic epitopes of HEV capsid (mimotopes). We identified putative linear and conformational mimotopes using sera from Scottish blood donors that have the immunological imprint of past HEV infection. Four mimotopes did not have homology with the primary sequence of HEV ORF2 capsid but competed effectively with a commercial HEV antigen for binding to anti-HEV reference serum. When the reactivity profile of each mimotope was compared with Wantai HEV-IgG ELISA, the most sensitive HEV immunoassay, mimotopes showed 95.2-100% sensitivity while the specificity ranged from 81.5 to 95.8%. PepSurf algorithm was used to map affinity-selected peptides onto the ORF2 crystal structure of HEV genotype 3, which predicted that these four mimototopes are clustered in the P domain of ORF2 capsid, near conformational epitopes of anti-HEV neutralising monoclonal antibodies. These HEV mimotopes may have potential applications in the design of structural vaccines and the development of new diagnostic tests.

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Hepatitis E Virus Mutations: Functional and Clinical Relevance

Cited by 60 publications

References 117 publications

Seroprevalence and incidence of hepatitis E virus among blood donors: A review

Seroprevalence and incidence of hepatitis E virus among blood donors: A review

Comprehensive Molecular Approach for Characterization of Hepatitis E Virus Genotype 3 Variants

Phage-displayed peptides that mimic epitopes of hepatitis E virus capsid

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