Amino acid sequence analysis in patients with chronic HCV genotype 1b infection during pegylated interferon-α2a and ribavirin therapy

Abstract

Background: Amino acid variations in several HCV genomic regions have been reported to be associated with response to interferon (IFN)-α plus ribavirin (RBV) combination therapy. However, the results remain controversial. In this study, we further investigated the amino acid variation of full-length HCV genome and its correlation to the response to pegylated interferon (PEG-IFN)-α2a and RBV combination therapy in patients with HCV genotype 1b (HCV-1b).

Methods: We retrospectively analysed 18 chronic HCV-1b patients (9 with rapid virological response and 9 non-response to therapy) treated with PEG-IFN-α2a plus RBV for 48 weeks. The nearly full-length HCV genome sequence was amplified by reverse transcription (RT)-PCR followed by cloning and sequencing. Genetic diversity differences between two groups were analysed including the number of amino acid variations in the HCV polyprotein and the mean pair-wise protein distance.

Results: No single amino acid variations were closely associated with treatment outcome. However, the number of amino acid mutations in the NS5B region especially in the thumb domain and in the NS5A-V3 region was associated with the response to PEG-IFN-α/RBV therapy (P=0.002 and P=0.029, respectively). The number of substitutions in the NS5B region was significantly correlated with the numbers of substitutions in the V3 region (r=0.568, P=0.027).

Conclusions: Amino acid substitutions in the NS5B region especially in the thumb domain and the NS5A-V3 region may play a role in the response to combined PEG-IFN-α2a and RBV therapy in HCV-1b patients.