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.