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      Determination of the full-genome sequence of hepatitis E virus (HEV) SAAS-FX17 and use as a reference to identify putative HEV genotype 4 virulence determinants

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          Abstract

          Background

          Four major genotypes of hepatitis E virus (HEV), the causative agent of hepatitis E, have so far been recognized. While genotypes 3 and 4 are both zoonotic, the disease symptoms caused by the latter tend to be more severe. To examine if specific nucleotide/amino acid variations between genotypes 3 and 4 play a role in determining the severity of hepatitis E disease, the complete genome of one swine HEV genotype 4 isolate, SAAS-FX17, was determined and compared with other genotype 4 and genotype 3 genomes to identify putative HEV genotype 4 virulence determinants.

          Results

          A total of 42 conformable nt/aa variations between genotype 3 and 4 HEVs were detected, of which 19 were proposed to be potential disease severity determinants for genotype 4 strains.

          Conclusions

          One potential determinant was located in each of the 5'-UTR and 3'-UTR, 3 and 12 within ORF1 and ORF2 respectively, and 2 in the junction region.

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          Most cited references28

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          A novel virus in swine is closely related to the human hepatitis E virus.

          X. J. Meng, R Purcell, P G Halbur … (1997)
          A novel virus, designated swine hepatitis E virus (swine HEV), was identified in pigs. Swine HEV crossreacts with antibody to the human HEV capsid antigen. Swine HEV is a ubiquitous agent and the majority of swine >/=3 months of age in herds from the midwestern United States were seropositive. Young pigs naturally infected by swine HEV were clinically normal but had microscopic evidence of hepatitis, and developed viremia prior to seroconversion. The entire ORFs 2 and 3 were amplified by reverse transcription-PCR from sera of naturally infected pigs. The putative capsid gene (ORF2) of swine HEV shared about 79-80% sequence identity at the nucleotide level and 90-92% identity at the amino acid level with human HEV strains. The small ORF3 of swine HEV had 83-85% nucleotide sequence identity and 77-82% amino acid identity with human HEV strains. Phylogenetic analyses showed that swine HEV is closely related to, but distinct from, human HEV strains. The discovery of swine HEV not only has implications for HEV vaccine development, diagnosis, and biology, but also raises a potential public health concern for zoonosis or xenozoonosis following xenotransplantation with pig organs.
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            Cross-species infections of cultured cells by hepatitis E virus and discovery of an infectious virus-host recombinant.

            Suzanne Emerson, Udana Torian, Lan T H Nguyễn … (2011)
            The RNA virus, hepatitis E virus (HEV) is the most or second-most important cause of acute clinical hepatitis in adults throughout much of Asia, the Middle East, and Africa. In these regions it is an important cause of acute liver failure, especially in pregnant women who have a mortality rate of 20-30%. Until recently, hepatitis E was rarely identified in industrialized countries, but Hepatitis E now is reported increasingly throughout Western Europe, some Eastern European countries, and Japan. Most of these cases are caused by genotype 3, which is endemic in swine, and these cases are thought to be zoonotically acquired. However, transmission routes are not well understood. HEV that infect humans are divided into nonzoonotic (types 1, 2) and zoonotic (types 3, 4) genotypes. HEV cell culture is inefficient and limited, and thus far HEV has been cultured only in human cell lines. The HEV strain Kernow-C1 (genotype 3) isolated from a chronically infected patient was used to identify human, pig, and deer cell lines permissive for infection. Cross-species infections by genotypes 1 and 3 were studied with this set of cultures. Adaptation of the Kernow-C1 strain to growth in human hepatoma cells selected for a rare virus recombinant that contained an insertion of 174 ribonucleotides (58 amino acids) of a human ribosomal protein gene.
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              Hepatitis E virus (HEV): molecular cloning and sequencing of the full-length viral genome.

              A W Tam, M M Smith, M E Guerra … (1991)
              We have recently described the cloning of a portion of the hepatitis E virus (HEV) and confirmed its etiologic association with enterically transmitted (waterborne, epidemic) non-A, non-B hepatitis. The virus consists of a single-stranded, positive-sense RNA genome of approximately 7.5 kb, with a polyadenylated 3' end. We now report on the cloning and nucleotide sequencing of an overlapping, contiguous set of cDNA clones representing the entire genome of the HEV Burma strain [HEV(B)]. The largest open reading frame extends approximately 5 kb from the 5' end and contains the RNA-directed RNA polymerase and nucleoside triphosphate binding motifs. The second major open reading frame (ORF2) begins 37 bp downstream of the first and extends approximately 2 kb to the termination codon present 65 bp from the 3' terminal stretch of poly(A) residues. ORF2 contains a consensus signal peptide sequence at its amino terminus and a capsid-like region with a high content of basic amino acids similar to that seen with other virus capsid proteins. A third open reading frame partially overlaps the first and second and encompasses only 369 bp. In addition to the 7.5-kb full-length genomic transcript, two subgenomic polyadenylated messages of approximately 3.7 and 2.0 kb were detected in infected liver using a probe from the 3' third of the genome. The genomic organization of the virus is consistent with the 5' end encoding nonstructural and the 3' end encoding the viral structural gene(s). The expression strategy of the virus involves the use of three different open reading frames and at least three different transcripts. HEV was previously determined to be a nonenveloped particle with a diameter of 27-34 nm. These findings on the genetic organization and expression strategy of HEV suggest that it is the prototype human pathogen for a new class of RNA virus or perhaps a separate genus within the Caliciviridae family.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Virol J
                Journal ID (iso-abbrev): Virol. J
                Title: Virology Journal
                Publisher: BioMed Central
                ISSN (Electronic): 1743-422X
                Publication date Collection: 2012
                Publication date (Electronic): 8 November 2012
                Volume: 9
                Page: 264
                Affiliations
                [1 ]Institute of Animal Science and Veterinary Medicine, Shanghai Academy of Agricultural Sciences, Shanghai, 201106, China
                [2 ]Shanghai Key Laboratory of Agricultural Genetics and Breeding, Shanghai, 201106, China
                [3 ]Veterinary College, Nanjing Agricultural University, Nanjing, Jiangsu, 210095, China
                [4 ]College of Animal Science and Technology, Jiangxi Agricultural University, Nanchang, Jiangxi, 330000, China
                Article
                Publisher ID: 1743-422X-9-264
                DOI: 10.1186/1743-422X-9-264
                PMC ID: 3546022
                PubMed ID: 23134633
                SO-VID: 6cbec3ab-972d-4065-9594-10c03d3e154b
                Copyright © Copyright ©2012 Zhu et al.; licensee BioMed Central Ltd.
                License:

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 15 June 2012
                Date accepted : 30 October 2012
                Categories
                Subject: Research

                ScienceOpen disciplines: Microbiology & Virology
                Keywords: disease severity determinant,zoonosis,genotype,hepatitis e virus,subtype
                Data availability:
                ScienceOpen disciplines: Microbiology & Virology
                Keywords: disease severity determinant, zoonosis, genotype, hepatitis e virus, subtype

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