Relation of pretreatment sequence diversity in NS5A region of HCV genotype 1 with immune response between pegylated-INF/ribavirin therapy outcomes.

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J Viral Hepat. 2010 Apr 27. [Epub ahead of print]

Relation of pretreatment sequence diversity in NS5A region of HCV genotype 1

with immune response between pegylated-INF/ribavirin therapy outcomes.

de Queiróz AT, Maracaja-Coutinho V, Jardim AC, Rahal P, de Carvalho-Mello IM,

Matioli SR.

Department of Genetics and Evolutive Biology, Biosciences Institute, USP - São

o University.

Abstract

Summary. Hepatitis C virus (HCV) infection frequently persists despite

substantial virus-specific immune responses and the combination of pegylated

interferon (INF)-alpha and ribavirin therapy. Major histocompatibility complex

class I restricted CD8(+) T cells are responsible for the control of viraemia in

HCV infection, and several studies suggest protection against viral infection

associated with specific HLAs. The reason for low rates of sustained viral

response (SVR) in HCV patients remains unknown. Escape mutations in response to

cytotoxic T lymphocyte are widely described; however, its influence in the

treatment outcome is ill understood. Here, we investigate the differences in CD8

epitopes frequencies from the Los Alamos database between groups of patients

that showed distinct response to pegylated alpha-INF with ribavirin therapy and

test evidence of natural selection on the virus in those who failed treatment,

using five maximum likelihood evolutionary models from PAML package. The group

of sustained virological responders showed three epitopes with frequencies

higher than Non-responders group, all had statistical support, and we observed

evidence of selection pressure in the last group. No escape mutation was

observed. Interestingly, the epitope VLSDFKTWL was 100% conserved in SVR group.

These results suggest that the response to treatment can be explained by the

increase in immune pressure, induced by interferon therapy, and the presence of

those epitopes may represent an important factor in determining the outcome of

therapy.

PMID: 20456637 [PubMed - as supplied by publisher]

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