Relation of pretreatment sequence diversity in NS5A region of HCV genotype 1 with immune response between pegylated-INF/ribavirin therapy outcomes

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dc.contributor.authorde Queiroz, A. T. L.
dc.contributor.authorMaracaja-Coutinho, V.
dc.contributor.authorJardim, A. C. G. [UNESP]
dc.contributor.authorRahal, Paula [UNESP]
dc.contributor.authorde Carvalho-Mello, I. M. V. G.
dc.contributor.authorMatioli, S. R.
dc.contributor.institutionInstituto Butantan
dc.contributor.institutionUniversidade de São Paulo (USP)
dc.contributor.institutionUniversidade Estadual Paulista (Unesp)
dc.date.accessioned2014-05-20T14:01:03Z
dc.date.available2014-05-20T14:01:03Z
dc.date.issued2011-02-01
dc.description.abstractHepatitis C virus (HCV) infection frequently persists despite substantial virus-specific immune responses and the combination of pegylated interferon (INF)-alpha and ribavirin therapy. Major histocompatibility complex class I restricted CD8+ T cells are responsible for the control of viraemia in HCV infection, and several studies suggest protection against viral infection associated with specific HLAs. The reason for low rates of sustained viral response (SVR) in HCV patients remains unknown. Escape mutations in response to cytotoxic T lymphocyte are widely described; however, its influence in the treatment outcome is ill understood. Here, we investigate the differences in CD8 epitopes frequencies from the Los Alamos database between groups of patients that showed distinct response to pegylated alpha-INF with ribavirin therapy and test evidence of natural selection on the virus in those who failed treatment, using five maximum likelihood evolutionary models from PAML package. The group of sustained virological responders showed three epitopes with frequencies higher than Non-responders group, all had statistical support, and we observed evidence of selection pressure in the last group. No escape mutation was observed. Interestingly, the epitope VLSDFKTWL was 100% conserved in SVR group. These results suggest that the response to treatment can be explained by the increase in immune pressure, induced by interferon therapy, and the presence of those epitopes may represent an important factor in determining the outcome of therapy.en
dc.description.affiliationInst Butantan, Viral Immunol Lab, BR-05503900 São Paulo, Brazil
dc.description.affiliationUniv São Paulo, Biosci Inst, Dept Genet & Evolut Biol, BR-05508 São Paulo, Brazil
dc.description.affiliationUniv São Paulo, Inst Chem, Dept Biochem, BR-05508 São Paulo, Brazil
dc.description.affiliationSão Paulo State Univ, UNESP Inst Biociencias Letras & Ciencias Exatas, Dept Biol, São Paulo, Brazil
dc.description.affiliationUnespSão Paulo State Univ, UNESP Inst Biociencias Letras & Ciencias Exatas, Dept Biol, São Paulo, Brazil
dc.description.sponsorshipCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
dc.format.extent142-148
dc.identifierhttp://dx.doi.org/10.1111/j.1365-2893.2010.01294.x
dc.identifier.citationJournal of Viral Hepatitis. Malden: Wiley-blackwell Publishing, Inc, v. 18, n. 2, p. 142-148, 2011.
dc.identifier.doi10.1111/j.1365-2893.2010.01294.x
dc.identifier.issn1352-0504
dc.identifier.lattes7991082362671212
dc.identifier.orcid0000-0001-5693-6148
dc.identifier.urihttp://hdl.handle.net/11449/21574
dc.identifier.wosWOS:000286257200009
dc.language.isoeng
dc.publisherWiley-Blackwell Publishing, Inc
dc.relation.ispartofJournal of Viral Hepatitis
dc.relation.ispartofjcr4.237
dc.relation.ispartofsjr1,683
dc.rights.accessRightsAcesso restrito
dc.sourceWeb of Science
dc.subjectGenotype 1en
dc.subjectHepatitis C virusen
dc.subjecthepatitisen
dc.subjectImmune responseen
dc.subjectNS5Aen
dc.titleRelation of pretreatment sequence diversity in NS5A region of HCV genotype 1 with immune response between pegylated-INF/ribavirin therapy outcomesen
dc.typeArtigo
dcterms.licensehttp://olabout.wiley.com/WileyCDA/Section/id-406071.html
dcterms.rightsHolderWiley-blackwell Publishing, Inc
unesp.author.lattes7991082362671212[4]
unesp.author.orcid0000-0001-5693-6148[4]
unesp.campusUniversidade Estadual Paulista (Unesp), Instituto de Biociências Letras e Ciências Exatas, São José do Rio Pretopt

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