Natural variability of NS3 protease in patients infected with genotype 4 hepatitis C virus (HCV): implications for antiviral treatment using specifically targeted antiviral therapy for HCV.

To analyze the genetic diversity of the NS3 gene in patients infected with hepatitis C virus (HCV) genotype 4 (HCV-4) and to assess the possible effects of the gene polymorphism (or variability) on drug susceptibility, 43 NS3 gene sequences were determined for 53 selected patients with HCV-4 infection. NS3 sequencing, like NS5B sequencing, allowed correct subtype determination. Most residues that were located within the catalytic triad or the NS4-binding region or that were involved in metal binding were highly conserved and identical to those found in HCV genotype 1. Compared with HCV genotype 1, all HCV-4 NS3 protein presented V36L and C16T residue changes that could potentially reduce antiprotease activity. The efficacy of antiprotease in HCV-4-infected patients remains to be proven in large clinical trials.