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.
Akhavan
S
S
Department of Virology, Hôpital Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris, and Université Pierre et Marie Curie Equipe de Recherche 1 Paris 6 University, Paris, France.
Schnuriger
A
A
Lebray
P
P
Benhamou
Y
Y
Poynard
T
T
Thibault
V
V
D000595:Amino Acid Sequence; D000998:Antiviral Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D015967:Gene Expression Regulation, Viral / Q000502:physiology; D014644:Genetic Variation; D005838:Genotype; D016174:Hepacivirus / Q000145:classification / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D010802:Phylogeny; D016133:Polymerase Chain Reaction; D017361:Viral Nonstructural Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
D000998:Antiviral Agents; D017361:Viral Nonstructural Proteins; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases