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

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Citações na Scopus
10
Tipo de produção
article
Data de publicação
2013
Título da Revista
ISSN da Revista
Título do Volume
Editora
PUBLIC LIBRARY SCIENCE
Autores
BITTAR, Cintia
JARDIM, Ana Carolina Gomes
YAMASAKI, Lilian Hiromi Tomonari
CARARETO, Claudia Marcia Aparecida
LEMEY, Philippe
CARVALHO-MELLO, Isabel Maria Vicente Guedes de
RAHAL, Paula
Citação
PLOS ONE, v.8, n.4, article ID e62393, 13p, 2013
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
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.
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