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Open Access 01-12-2013 | Research article

Analysis of HCV quasispecies dynamic under selective pressure of combined therapy

Authors: Ana CG Jardim, Cíntia Bittar, Renata PA Matos, Lílian HT Yamasaki, Rafael A Silva, João RR Pinho, Roberta M Fachini, Claudia MA Carareto, Isabel MVG de Carvalho-Mello, Paula Rahal

Published in: BMC Infectious Diseases | Issue 1/2013

Abstract

Background

The quasispecies composition of Hepatitis C virus (HCV) could have important implications with regard to viral persistence and response to interferon-based therapy. The complete NS5A was analyzed to evaluate whether the composition of NS5A quasispecies of HCV 1a/1b is related to responsiveness to combined interferon pegylated (PEG-IFN) and ribavirin therapy.

Methods

Viral RNA was isolated from serum samples collected before, during and after treatment from virological sustained responder (SVR), non-responder (NR) and the end-of-treatment responder patients (ETR). NS5A region was amplified, cloned and sequenced. Six hundred and ninety full-length NS5A sequences were analyzed.

Results

This study provides evidence that lower nucleotide diversity of the NS5A region pre-therapy is associated with viral clearance. Analysis of samples of NRs and the ETRs time points showed that genetic diversity of populations tend to decrease over time. Post-therapy population of ETRs presented higher genetic distance from baseline probably due to the bottleneck phenomenon observed for those patients in the end of treatment. The viral effective population of those patients also showed a strong decrease after therapy. Otherwise, NRs demonstrated a continuous variation or stability of effective populations and genetic diversity over time that did not seem to be related to therapy. Phylogenetic relationships concerning complete NS5A sequences obtained from patients did not demonstrate clustering associated with specific response patterns. However, distinctive clustering of pre/post-therapy sequences was observed. In addition, the evolution of quasispecies over time was subjected to purifying or relaxed purifying selection. Codons 157 (P03), 182 and 440 (P42), 62 and 404 (P44) were found to be under positive selective pressure but it failed to be related to the therapy.

Conclusion

These results confirm the hypothesis that a relationship exists between NS5A heterogeneity and response to therapy in patients infected with chronic hepatitis C.

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The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2334/13/61/prepub

Title: Analysis of HCV quasispecies dynamic under selective pressure of combined therapy
Authors: Ana CG Jardim
Cíntia Bittar
Renata PA Matos
Lílian HT Yamasaki
Rafael A Silva
João RR Pinho
Roberta M Fachini
Claudia MA Carareto
Isabel MVG de Carvalho-Mello
Paula Rahal
Publication date: 01-12-2013
Publisher: BioMed Central
Published in: BMC Infectious Diseases / Issue 1/2013
Electronic ISSN: 1471-2334
DOI: https://doi.org/10.1186/1471-2334-13-61

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