Quasispecies of hepatitis C virus genotype 1 and treatment outcome with Peginterferon and Ribavirin

dc.contributor.authorGomes Jardim, Ana Carolina [UNESP]
dc.contributor.authorTomonari Yamasaki, Lilian Hiromi [UNESP]
dc.contributor.authorLopo de Queiroz, Artur Trancoso
dc.contributor.authorBittar, Cintia [UNESP]
dc.contributor.authorRebello Pinho, Joao Renato
dc.contributor.authorAparecida Carareto, Claudia Marcia [UNESP]
dc.contributor.authorRahal, Paula [UNESP]
dc.contributor.authorGuedes de Carvalho Mello, Isabel Maria Vicente
dc.contributor.institutionUniversidade Estadual Paulista (Unesp)
dc.contributor.institutionUniversidade de São Paulo (USP)
dc.contributor.institutionInstituto Butantan
dc.date.accessioned2014-05-20T14:00:50Z
dc.date.available2014-05-20T14:00:50Z
dc.date.issued2009-07-01
dc.description.abstractThe majority of patients with chronic hepatitis C fail to respond to antiviral therapy. The genetic basis of this resistance is unknown. The quasispecies nature of HCV may have an important implication concerning viral persistence and response to therapy. The HCV nonstructural 5A (NS5A) protein has been controversially implicated in the inherent resistance of HCV to interferon (IFN) antiviral therapy. To evaluate whether the NS5A quasispecies pre-treatment composition of HCV 1a/1b is related to responsiveness to combined pegylated interferon (PEG-IFN) and Ribavirin therapy, detailed analyses of the complete NS5A were performed. Fifteen full-length NS5A clones were sequenced from 11 pretreatment samples of patients infected with genotype 1 HCV (3 virological sustained responders, 4 non-responders, and 4 end-of-treatment responders). Our study could not show a significant correlation between the mean number of mutations in HCV NS5A before treatment and treatment outcome, and the phylogenetic construction of complete NS5A sequences obtained from all patients failed to show any clustering associated with a specific response pattern. No single amino acid position was associated with different responses to therapy in any of the NS5A regions analyzed, and mutations were clustered downstream the ISDR, primarily in the V3 region. We observed that the CRS and NLS regions of the NS5A protein were conflicting for some variables analyzed, although no significant differences were found. If these two regions can have antagonistic functions, it seems viable that they present different mutation profiles when compared with treatment response. The patient sample that presented the lowest genetic distance values also presented the smallest number of variants, and the most heterogeneous pattern was seen in the end-of-treatment patients. These results suggest that a detailed molecular analysis of the NS5A region on a larger sample size may be necessary for understanding its role in the therapy outcome of HCV 1a/1b infection. (C) 2008 Elsevier B.V. All rights reserved.en
dc.description.affiliationUniv Estadual Paulista, Inst Biociencias Letras & Ciencias Exatas, São Paulo State Univ,Dept Biol, Inst Biosci Language & Literature & Exact Sci, BR-15054000 Sao Jose do Rio Preto, SP, Brazil
dc.description.affiliationUniv São Paulo, Inst Biosci, São Paulo, Brazil
dc.description.affiliationUniv São Paulo, Inst Math & Stat, São Paulo, Brazil
dc.description.affiliationUniv São Paulo, Fac Med, Inst Trop Med, Lab Hepatol & Gastroenterol,Dept Gastroenterol, São Paulo, Brazil
dc.description.affiliationInstituto Butantan, Viral Immunol Lab, São Paulo, Brazil
dc.description.affiliationUnespUniv Estadual Paulista, Inst Biociencias Letras & Ciencias Exatas, São Paulo State Univ,Dept Biol, Inst Biosci Language & Literature & Exact Sci, BR-15054000 Sao Jose do Rio Preto, SP, Brazil
dc.format.extent689-698
dc.identifierhttp://dx.doi.org/10.1016/j.meegid.2008.11.001
dc.identifier.citationInfection Genetics and Evolution. Amsterdam: Elsevier B.V., v. 9, n. 4, p. 689-698, 2009.
dc.identifier.doi10.1016/j.meegid.2008.11.001
dc.identifier.issn1567-1348
dc.identifier.lattes7991082362671212
dc.identifier.orcid0000-0001-5693-6148
dc.identifier.urihttp://hdl.handle.net/11449/21489
dc.identifier.wosWOS:000267044800038
dc.language.isoeng
dc.publisherElsevier B.V.
dc.relation.ispartofInfection, Genetics and Evolution
dc.relation.ispartofjcr2.545
dc.relation.ispartofsjr1,278
dc.rights.accessRightsAcesso aberto
dc.sourceWeb of Science
dc.subjectHepatitis C virusen
dc.subjectGenotype 1en
dc.subjectQuasispeciesen
dc.subjectNonstructural 5A regionen
dc.subjectPegylated interferonen
dc.subjectRibavirinen
dc.subjectSequence analysisen
dc.titleQuasispecies of hepatitis C virus genotype 1 and treatment outcome with Peginterferon and Ribavirinen
dc.typeTrabalho apresentado em evento
dcterms.licensehttp://www.elsevier.com/about/open-access/open-access-policies/article-posting-policy
dcterms.rightsHolderElsevier B.V.
unesp.author.lattes7991082362671212[7]
unesp.author.orcid0000-0001-5693-6148[7]
unesp.campusUniversidade Estadual Paulista (Unesp), Instituto de Biociências Letras e Ciências Exatas, São José do Rio Pretopt

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