Phylogenetic and structural analysis of HCV nonstructural protein 4A from Pakistani patients.

Hepatitis C virus nonstructural protein, NS4A, is a small protein comprising of about 54 amino acids. Despite its small size, it plays key role in many viral and cellular functions. The most important of which is its role as the co-factor of viral serine protease and helicase (NS3). Our study examines the phylogenetic and structural analysis of this coding region after isolation from Pakistani HCV patient samples. Phylogenetic analysis of the gene revealed that Pakistani 3a HCV strains do not show significant divergence from those reported from the rest of the world. The findings of this study also depict that NS4A sequence is conserved within genotypes, whereas it shows variations among different genotypes. While predicting the tertiary structure of the protein two important mutations (H28Y & E32G) were observed when comparing the Pakistani sequences with that of a reference HCV (genotype 3a) strain NZL (D17763). These mutations were observed in the central domain of NS4A which is responsible for interaction with NS3. Taken together, these mutations within the NS4A coding region can play an important role in the binding capacity of NS4A with HCV serine protease NS3.