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      Hepatitis E Virus Genotypes and Evolution: Emergence of Camel Hepatitis E Variants

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          Abstract

          Hepatitis E virus (HEV) is a major cause of viral hepatitis globally. Zoonotic HEV is an important cause of chronic hepatitis in immunocompromised patients. The rapid identification of novel HEV variants and accumulating sequence information has prompted significant changes in taxonomy of the family Hepeviridae. This family includes two genera: Orthohepevirus, which infects terrestrial vertebrates, and Piscihepevirus, which infects fish. Within Orthohepevirus, there are four species, A–D, with widely differing host range. Orthohepevirus A contains the HEV variants infecting humans and its significance continues to expand with new clinical information. We now recognize eight genotypes within Orthohepevirus A: HEV1 and HEV2, restricted to humans; HEV3, which circulates among humans, swine, rabbits, deer and mongooses; HEV4, which circulates between humans and swine; HEV5 and HEV6, which are found in wild boars; and HEV7 and HEV8, which were recently identified in dromedary and Bactrian camels, respectively. HEV7 is an example of a novel genotype that was found to have significance to human health shortly after discovery. In this review, we summarize recent developments in HEV molecular taxonomy, epidemiology and evolution and describe the discovery of novel camel HEV genotypes as an illustrative example of the changes in this field.

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          Most cited references57

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          Proposed reference sequences for hepatitis E virus subtypes

          The nomenclature of hepatitis E virus (HEV) subtypes is inconsistent and makes comparison of different studies problematic. We have provided a table of proposed complete genome reference sequences for each subtype. The criteria for subtype assignment vary between different genotypes and methodologies, and so a conservative pragmatic approach has been favoured. Updates to this table will be posted on the International Committee on Taxonomy of Viruses website (http://talk.ictvonline.org/r.ashx?C). The use of common reference sequences will facilitate communication between researchers and help clarify the epidemiology of this important human pathogen. This subtyping procedure might be adopted for other taxa of the genus Orthohepevirus.
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            Analysis of the full-length genome of a hepatitis E virus isolate obtained from a wild boar in Japan that is classifiable into a novel genotype.

            While performing a nationwide survey of hepatitis E virus (HEV) infection among 450 wild boars (Sus scrofa leucomystax) that had been captured in Japan between November 2005 and March 2010, we found 16 boars (3.6%) with ongoing HEV infection: 11 had genotype 3 HEV, four had genotype 4 HEV and the remaining boar was infected with HEV of an unrecognized genotype (designated wbJOY_06). The entire wbJOY_06 genome was sequenced and was found to comprise 7246 nt excluding the poly(A) tail. The wbJOY_06 isolate was highly divergent from known genotype 1-4 HEV isolates derived from humans, swine, wild boars, deer, mongoose and rabbits (n=145) by 22.6-27.7%, rat HEV isolates (n=2) by 46.0-46.2%, and avian HEV isolates (n=5) by 52.5-53.1% over the entire genome. A Simplot analysis revealed no significant recombination between the existing HEV strains of genotypes 1-4. Therefore, we propose that the wbJOY_06 isolate is the first member of a previously unidentified genotype.
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              A bicistronic subgenomic mRNA encodes both the ORF2 and ORF3 proteins of hepatitis E virus.

              Hepatitis E virus replicons containing the neomycin resistance gene expressed from open reading frames (ORFs) 2 and 3 were transfected into Huh-7 cells, and stable cell lines containing functional replicons were selected by constant exposure to G418 sulfate. Northern blot analyses detected full-length replicon RNA and a single subgenomic RNA. This subgenomic RNA, which was capped, initiated at nucleotide 5122 downstream of the first two methionine codons in ORF3 and was bicistronic; two closely spaced methionine codons in different reading frames were used for the initiation of ORF3 and ORF2 translation.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                Int J Mol Sci
                Int J Mol Sci
                ijms
                International Journal of Molecular Sciences
                MDPI
                1422-0067
                20 April 2017
                April 2017
                : 18
                : 4
                : 869
                Affiliations
                [1 ]Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China; sid8998@ 123456gmail.com (S.S.); llteng@ 123456hku.hk (J.L.L.T.); tsz.chiu@ 123456uqconnect.edu.au (T.-H.C.); skplau@ 123456hku.hk (S.K.P.L.)
                [2 ]State Key Laboratory of Emerging Infectious Diseases, Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, University Pathology Building, Queen Mary Hospital, Hong Kong, China
                [3 ]Research Centre of Infection and Immunology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
                [4 ]Carol Yu Centre for Infection, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
                Author notes
                [* ]Correspondence: pcywoo@ 123456hku.hk ; Tel.: +852-22-554-892; Fax: +852-28-551-241
                Article
                ijms-18-00869
                10.3390/ijms18040869
                5412450
                28425927
                72c68eb6-2adb-47da-873a-99d24f68b65a
                © 2017 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 27 March 2017
                : 18 April 2017
                Categories
                Review

                Molecular biology
                hepatitis e,zoonosis,hepatitis,taxonomy,molecular evolution,molecular epidemiology,genotypes,dromedary camel,bactrian camel,swine

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