Insights into the unique characteristics of hepatitis C virus genotype 3 revealed by development of a robust sub-genomic DBN3a replicon

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dc.contributor.authorWard, Joseph C.
dc.contributor.authorBowyer, Sebastian
dc.contributor.authorChen, Shucheng
dc.contributor.authorCampos, Guilherme Rodrigues Fernandes [UNESP]
dc.contributor.authorRamirez, Santseharay
dc.contributor.authorBukh, Jens
dc.contributor.authorHarris, Mark
dc.contributor.institutionUniv Leeds
dc.contributor.institutionHvidovre Univ Hosp
dc.contributor.institutionUniv Copenhagen
dc.contributor.institutionUniversidade Estadual Paulista (Unesp)
dc.date.accessioned2021-06-25T11:44:58Z
dc.date.available2021-06-25T11:44:58Z
dc.date.issued2020-01-01
dc.description.abstractHepatitis C virus (HCV) is an important human pathogen causing 400 000 chronic liver disease-related deaths annually. Until recently, the majority of laboratory-based investigations into the biology of HCV have focused on the genotype 2 isolate, JFH-1, involving replicons and infectious cell culture systems. However, genotype 2 is one of eight major genotypes of HCV and there is great sequence variation among these genotypes (>30% nucleotide divergence). In this regard, genotype 3 is the second most common genotype and accounts for 30% of global HCV cases. Further, genotype 3 is associated with both high levels of inherent resistance to direct-acting antiviral (DAA) therapy, and a more rapid progression to chronic liver diseases. Neither of these two attributes are fully understood, thus robust genotype 3 culture systems to unravel viral replication are required. Here we describe the generation of robust genotype 3 sub-genomic replicons (SGRs) based on the adapted HCV NS3-NS5B replicase from the DBN3a cell culture infectious clone. Such infectious cell culture-adaptive mutations could potentially promote the development of robust SGRs for other HCV strains and genotypes. The novel genotype 3 SGRs have been used both transiently and to establish stable SGR-harbouring cell lines. We show that these resources can be used to investigate aspects of genotype 3 biology, including NS5A function and DAA resistance. They will be useful tools for these studies, circumventing the need to work under the biosafety level 3 (BSL3) containment required in many countries.en
dc.description.affiliationUniv Leeds, Fac Biol Sci, Sch Mol & Cellular Biol, Leeds LS2 9JT, W Yorkshire, England
dc.description.affiliationUniv Leeds, Astbury Ctr Struct Mol Biol, Leeds LS2 9JT, W Yorkshire, England
dc.description.affiliationHvidovre Univ Hosp, Dept Infect Dis, Copenhagen Hepatitis C Program CO HEP, Kettegard Alle 30, DK-2650 Hvidovre, Denmark
dc.description.affiliationUniv Copenhagen, Fac Hlth & Med Sci, Dept Immunol & Microbiol, Blegdamsvej 3, DK-2200 Copenhagen N, Denmark
dc.description.affiliationSao Paulo State Univ, Inst Biosci Languages & Exact Sci, Cristovao Colombo St 2265, BR-15054000 Sao Jose Do Rio Preto, SP, Brazil
dc.description.affiliationUnespSao Paulo State Univ, Inst Biosci Languages & Exact Sci, Cristovao Colombo St 2265, BR-15054000 Sao Jose Do Rio Preto, SP, Brazil
dc.description.sponsorshipMRC
dc.description.sponsorshipChina Scholarship Council
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorshipNovo Nordisk Foundation
dc.description.sponsorshipIdMRC: MR/S001026/1
dc.description.sponsorshipIdFAPESP: 2016/03807-0
dc.description.sponsorshipIdFAPESP: 2018/04678-5
dc.description.sponsorshipIdNovo Nordisk Foundation: NNF19OC0054518
dc.format.extent1182-1190
dc.identifierhttp://dx.doi.org/10.1099/jgv.0.001486
dc.identifier.citationJournal Of General Virology. London: Microbiology Soc, v. 101, n. 11, p. 1182-1190, 2020.
dc.identifier.doi10.1099/jgv.0.001486
dc.identifier.issn0022-1317
dc.identifier.urihttp://hdl.handle.net/11449/208983
dc.identifier.wosWOS:000596371800006
dc.language.isoeng
dc.publisherMicrobiology Soc
dc.relation.ispartofJournal Of General Virology
dc.sourceWeb of Science
dc.subjecthepatitis C virus
dc.subjectsub-genomic replicon
dc.subjectgenotype 3
dc.subjectNS5A
dc.titleInsights into the unique characteristics of hepatitis C virus genotype 3 revealed by development of a robust sub-genomic DBN3a repliconen
dc.typeArtigo
dcterms.rightsHolderMicrobiology Soc
unesp.author.orcid0000-0002-5681-6813[2]
unesp.author.orcid0000-0003-1118-8486[4]
unesp.author.orcid0000-0003-3699-1814[5]
unesp.author.orcid0000-0002-7815-4806[6]
unesp.author.orcid0000-0002-9821-1003[7]

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