Sequence comparison and phylogenetic analysis of Hepatitis C virus genotype 3 polymerase

Abstract

Hepatitis C virus (HCV) is a worldwide health problem with high morbidity and mortality. HCV polymerase is an attractive target for the development of antiviral strategies. The aim of the present study was to report the sequence variation in the HCV NS5B gene from genotype 3 patient samples. The gene was amplified, cloned and sequenced. A nucleotide and amino acid sequence comparison of conserved motifs of HCV NS5B from the current reported sequences and previously reported genotype 3 sequences was performed. The sequence comparison indicated that the motifs A, B, C and F and β loop sequences are conserved in the reported sequences, while sequence variation was observed in motifs D and E. Amino acids E18, Y191, C274, Y276 and H502, which are involved in the interaction between template and primer, are highly conserved in the reported sequences. R48, R158, D225, S367, R386 and R394 amino acids interact with initiating GTP, and are also highly conserved in the reported sequences. A phylogenetic tree revealed that the sequences are clustered with sequences from India. HCV polymerase lacks proofreading ability and has high error rates. The present study revealed that the residues that form the important motifs of HCV NS5B remain conserved. However, it was observed that numerous place changes in the nucleotide sequences did not affect the amino acid sequences of HCV NS5B. The conserved motifs are strong targets for the development of peptide vaccines against HCV.