Mutations in nonstructural protein 5A gene and response to interferon in hepatitis C virus genotype 2 infection.
An association has been reported between mutations in the amino acid residues 2209-2248 of the nonstructural protein 5A (NS5A) gene (interferon-sensitivity determining region [ISDR]) and interferon efficacy in hepatitis C virus (HCV)-1b infection. This relationship was analyzed in chronic HCV-2 infection. Forty patients with HCV-2a and 35 with HCV-2b were treated with interferon alfa for 6 months with a total dose of 468 to 860 million units. Pretreatment NS5A sequences were determined by direct sequencing. A higher complete and sustained response rate was observed in HCV-2a than in HCV-2b (70% vs. 34%; P =.003). Serum HCV-RNA levels were lower in complete responders than nonresponders in HCV-2a (P =.049) and HCV-2b (P =. 02). The number of amino acid mutations was greater in complete responders than nonresponders in NS5A2193-2228 (the region corresponding to the ISDR of HCV-1b) alone (P =.049), or NS5A2163-2228 consisting of NS5A2193-2228 plus its upstream region (P =.02) in HCV-2a, but not in HCV-2b. A significant inverse correlation was observed between serum HCV-RNA levels and the number of amino acid mutations in NS5A2193-2228 (P =.003) or NS5A2163-2228 (P =.005) in HCV-2a. With multivariate analysis, the number of substitutions in NS5A was an independent predictor for complete response in HCV-2a (odds ratio: 6.4; P =.03). Interferon efficacy is associated with amino acid variations in the NS5A protein in HCV-2a infection.
Murakami
T
T
Second Department of Internal Medicine, Tokyo Medical and Dental University, Tokyo, Japan.
Enomoto
N
N
Kurosaki
M
M
Izumi
N
N
Marumo
F
F
Sato
C
C
D000328:Adult; D000595:Amino Acid Sequence / Q000235:genetics; D001483:Base Sequence / Q000235:genetics; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics*; D006526:Hepatitis C / Q000097:blood / Q000188:drug therapy* / Q000235:genetics*; D006801:Humans; D007372:Interferons / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D012367:RNA, Viral / Q000097:blood; D012189:Retrospective Studies; D017361:Viral Nonstructural Proteins / Q000235:genetics*; D012324:RNA-Dependent RNA Polymerase
D007372:Interferons; D012367:RNA, Viral; D017361:Viral Nonstructural Proteins; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase