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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

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

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Autor(es):
Bittar, Cintia [1] ; Gomes Jardim, Ana Carolina [1] ; Tomonari Yamasaki, Lilian Hiromi [1] ; Aparecida Carareto, Claudia Marcia [1] ; Rebello Pinho, Joao Renato [2, 3] ; Lemey, Philippe [4] ; Vicente Guedes de Carvalho-Mello, Isabel Maria [5] ; Rahal, Paula [1]
Número total de Autores: 8
Afiliação do(s) autor(es):
[1] UNESP Sao Paulo State Univ, IBILCE Inst Biosci Language & Literature & Exact, Dept Biol, Sao Paulo - Brazil
[2] Univ Sao Paulo, Fac Med, Dept Gastroenterol, Lab Hepatol & Gastroenterol, Inst Trop Med, Sao Paulo - Brazil
[3] Albert Einstein Israeli Hosp, Dept Clin Pathol, Sao Paulo - Brazil
[4] Katholieke Univ Leuven, Lab Clin & Epidemiol Virol, Rega Inst, Louvain - Belgium
[5] Univ Fed Sao Paulo, Escola Paulista Med, Dept Med, Disciplina Gastroenterol, Lab Hepatol Mol Aplicada, Sao Paulo - Brazil
Número total de Afiliações: 5
Tipo de documento: Artigo Científico
Fonte: PLoS One; v. 8, n. 4 APR 25 2013.
Citações Web of Science: 8
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. (AU)

Processo FAPESP: 06/60012-9 - Analise das quasiespecies de hcv na regiao ns5a do genotipo 1 e do genotipo 3 antes e apos o tratamento em pacientes nao respondedores ao tratamento.
Beneficiário:Paula Rahal
Modalidade de apoio: Auxílio à Pesquisa - Regular
Processo FAPESP: 08/51165-1 - Estudo da evolucao das quasiespecies da regiao ns5a de hcv genotipo 3a.
Beneficiário:Cintia Bittar Oliva
Modalidade de apoio: Bolsas no Brasil - Doutorado