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dc.contributor.authorCao, Dianjunen
dc.contributor.authorNi, Yan-Yanen
dc.contributor.authorMeng, Xiang-Jinen
dc.date.accessioned2018-02-12T13:52:24Zen
dc.date.available2018-02-12T13:52:24Zen
dc.date.issued2018-02-08en
dc.identifier.citationVirology Journal. 2018 Feb 08;15(1):32en
dc.identifier.urihttp://hdl.handle.net/10919/82058en
dc.description.abstractBackground Genotype 3 hepatitis E virus (HEV) infection is generally associated with mild disease. However, recently eight genotype 3 HEV isolates were identified from patients with severe hepatitis. Importantly, three mutations (S605P, I978V and V1213A) in these genotype 3 isolates were found to be typical of genotype 4 HEV, which is sometime associated with more severe hepatitis. Therefore in this study we seek to determine if these unique mutations contribute to enhanced virus replication and thus potentially severe disease. Methods In the lack of an efficient cell culture system to study the effect of mutations on HEV replication, we developed a genotype 3 HEV replicon with Renilla luciferase (Rluc) as reporter and subsequently used it to construct numerous mutants, including swMu-1 (V1213A), swMu-2 (Q1246H), swMu-3 (V1213A and Q1246H), swMu-4 (S605P and I978V), and swMu-5 (V1213A, S605P and I978V). RNA transcripts from mutant replicons were transfected into Huh7 S10–3 liver cells to measure the effect of mutations on HEV replication efficiency. Results The results showed that the V1213A mutant had the highest reduction in HEV replication efficiency than other mutants. The V1213A and S605P + I978V mutations have a cumulative, if not synergistic, effect on HEV replication. The Q1246H mutant decreased HEV replication compared to the wild-type HEV Rluc replicon but replicated better than the V1213A mutant. The amino acid residue V1213 favors the replication of both genotypes 3 and 4 HEV strains, but not genotype 1 HEV. Conclusion The results suggested that the V1213A mutation reduced HEV replication, but is likely not associated with the reported severe hepatitis caused by genotype 3 HEV isolates containing this mutation.en
dc.format.mimetypeapplication/pdfen
dc.language.isoen_USen
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.titleSubstitution of amino acid residue V1213 in the helicase domain of the genotype 3 hepatitis E virus reduces virus replicationen
dc.typeArticle - Refereeden
dc.date.updated2018-02-11T04:35:54Zen
dc.description.versionPublished versionen
dc.rights.holderThe Author(s)en
dc.title.serialVirology Journalen
dc.identifier.doihttps://doi.org/10.1186/s12985-018-0943-5en
dc.type.dcmitypeTexten


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Creative Commons Attribution 4.0 International
License: Creative Commons Attribution 4.0 International