On Hepatitis C Virus Evolution: the Interaction between Virus and Host towards Treatment Outcome

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dc.contributor.author Bittar, Cintia
dc.contributor.author Gomes Jardim, Ana Carolina
dc.contributor.author Tomonari Yamasaki, Lilian Hiromi
dc.contributor.author Aparecida Carareto, Claudia Marcia
dc.contributor.author Rebello Pinho, Joao Renato
dc.contributor.author Lemey, Philippe
dc.contributor.author Mello, Isabel Maria Vicente Guedes de Carvalho [UNIFESP]
dc.contributor.author Rahal, Paula
dc.date.accessioned 2016-01-24T14:31:36Z
dc.date.available 2016-01-24T14:31:36Z
dc.date.issued 2013-04-25
dc.identifier http://dx.doi.org/10.1371/journal.pone.0062393
dc.identifier.citation Plos One. San Francisco: Public Library Science, v. 8, n. 4, 13 p., 2013.
dc.identifier.issn 1932-6203
dc.identifier.uri http://repositorio.unifesp.br/handle/11600/36220
dc.description.abstract Background: Hepatitis C is a disease spread throughout the world. Hepatitis C virus (HCV), the etiological agent of this disease, is a single-stranded positive RNA virus. Its genome encodes a single precursor protein that yields ten proteins after processing. NS5A, one of the non-structural viral proteins, is most associated with interferon-based therapy response, the approved treatment for hepatitis C in Brazil. HCV has a high mutation rate and therefore high variability, which may be important for evading the immune system and response to therapy. the aim of this study was to analyze the evolution of NS5A quasispecies before, during, and after treatment in patients infected with HCV genotype 3a who presented different therapy responses.Methods: Viral RNA was extracted, cDNA was synthesized, the NS5A region was amplified and cloned, and 15 clones from each time-point were sequenced. the sequences were analyzed for evolutionary history, genetic diversity and selection.Results: This analysis shows that the viral population that persists after treatment for most non-responder patients is present in before-treatment samples, suggesting it is adapted to evade treatment. in contrast, the population found in before treatment samples from most end-of-treatment responder patients either are selected out or appears in low frequency after relapse, therefore changing the population structure. the exceptions illustrate the uniqueness of the evolutionary process, and therefore the treatment resistance process, in each patient.Conclusion: Although evolutionary behavior throughout treatment showed that each patient presented different population dynamics unrelated to therapy outcome, it seems that the viral population from non-responders that resists the treatment already had strains that could evade therapy before it started. en
dc.description.sponsorship Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.format.extent 13
dc.language.iso eng
dc.publisher Public Library Science
dc.relation.ispartof Plos One
dc.rights Acesso aberto
dc.title On Hepatitis C Virus Evolution: the Interaction between Virus and Host towards Treatment Outcome en
dc.type Artigo
dc.contributor.institution UNESP São Paulo State Univ
dc.contributor.institution Universidade de São Paulo (USP)
dc.contributor.institution Albert Einstein Israeli Hosp
dc.contributor.institution Katholieke Univ Leuven
dc.contributor.institution Universidade Federal de São Paulo (UNIFESP)
dc.description.affiliation UNESP São Paulo State Univ, IBILCE Inst Biosci Language & Literature & Exact, Dept Biol, São Paulo, Brazil
dc.description.affiliation Univ São Paulo, Fac Med, Dept Gastroenterol, Lab Hepatol & Gastroenterol,Inst Trop Med, São Paulo, Brazil
dc.description.affiliation Albert Einstein Israeli Hosp, Dept Clin Pathol, São Paulo, Brazil
dc.description.affiliation Katholieke Univ Leuven, Lab Clin & Epidemiol Virol, Rega Inst, Louvain, Belgium
dc.description.affiliation Universidade Federal de São Paulo, Escola Paulista Med, Dept Med, Disciplina Gastroenterol,Lab Hepatol Mol Aplicada, São Paulo, Brazil
dc.description.affiliationUnifesp Universidade Federal de São Paulo, Escola Paulista Med, Dept Med, Disciplina Gastroenterol,Lab Hepatol Mol Aplicada, São Paulo, Brazil
dc.description.sponsorshipID FAPESP: 2008/51165-1
dc.description.sponsorshipID FAPESP: 2006/60012-9
dc.identifier.file WOS000318341400053.pdf
dc.identifier.doi 10.1371/journal.pone.0062393
dc.description.source Web of Science
dc.identifier.wos WOS:000318341400053



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