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

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.