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

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

Autor Bittar, Cintia Google Scholar
Gomes Jardim, Ana Carolina Google Scholar
Tomonari Yamasaki, Lilian Hiromi Google Scholar
Aparecida Carareto, Claudia Marcia Google Scholar
Rebello Pinho, Joao Renato Google Scholar
Lemey, Philippe Google Scholar
Mello, Isabel Maria Vicente Guedes de Carvalho Autor UNIFESP Google Scholar
Rahal, Paula Google Scholar
Instituição UNESP São Paulo State Univ
Universidade de São Paulo (USP)
Albert Einstein Israeli Hosp
Katholieke Univ Leuven
Universidade Federal de São Paulo (UNIFESP)
Resumo 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.
Idioma Inglês
Financiador Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Número do financiamento FAPESP: 2008/51165-1
FAPESP: 2006/60012-9
Data de publicação 2013-04-25
Publicado em Plos One. San Francisco: Public Library Science, v. 8, n. 4, 13 p., 2013.
ISSN 1932-6203 (Sherpa/Romeo, fator de impacto)
Publicador Public Library Science
Extensão 13
Fonte http://dx.doi.org/10.1371/journal.pone.0062393
Direito de acesso Acesso aberto Open Access
Tipo Artigo
Web of Science WOS:000318341400053
Endereço permanente http://repositorio.unifesp.br/handle/11600/36220

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