Amino acid substitutions in the nonstructural region 5A of hepatitis C virus genotypes 2a and 2b and its relation to viral load and response to interferon.
OBJECTIVE
The interferon sensitivity-determining region (ISDR) in nonstructural region 5A (NS5A) of hepatitis C virus genotype 1b has been reported to correlate with response to interferon therapy and viral load. Recently the correlation between NS5A and response to interferon in genotype 2a was also reported. We examined the region of genotypes 2a and 2b corresponding to the ISDR of genotype lb to elucidate its correlation with response to interferon and viral load.


METHODS
The sequences of amino acid positions 2213-2248 in NS5A were determined in 39 patients with genotype 2a and 12 patients with genotype 2b.


RESULTS
In the patients infected with genotype 2a, the number of amino acid substitutions in the ISDR-corresponding region compared with the consensus sequence of genotype 2a was significantly correlated with viral load (p = -0.541, p < 0.001) and with response to interferon therapy (p < 0.05); 83% of the patients with three or more substitutions obtained sustained responses, whereas only 44% of those with less than three substitutions obtained sustained responses. Multivariate analysis confirmed that the number of substitutions in the ISDR-corresponding region of genotype 2a was one of the independent predictors of response to interferon therapy (discriminant coefficient = 1.35, p < 0.001).


CONCLUSIONS
Substitutions in the ISDR-corresponding region in NS5A of hepatitis C virus genotype 2a was confirmed to correlate to viral load and response to interferon therapy. In genotype 2b, further work must be considered because of the small number of patients studied.
Kobayashi
Makoto
M
Third Department of Internal Medicine, Nagoya University School of Medicine, Japan.
Watanabe
Kazumasa
K
Ishigami
Masatoshi
M
Murase
Kenichi
K
Ito
Hiroshi
H
Ukai
Koji
K
Yano
Motoyoshi
M
Takagi
Kenji
K
Hattori
Masaki
M
Kakumu
Shinichi
S
Yoshioka
Kentaro
K
D024506:5' Flanking Region / Q000187:drug effects* / Q000235:genetics*; D000328:Adult; D019943:Amino Acid Substitution / Q000187:drug effects* / Q000235:genetics*; D000998:Antiviral Agents / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000187:drug effects* / Q000235:genetics*; D006526:Hepatitis C / Q000188:drug therapy / Q000235:genetics*; D006801:Humans; D007372:Interferons / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D019562:Viral Load; D017361:Viral Nonstructural Proteins / Q000187:drug effects* / Q000235:genetics*
D000998:Antiviral Agents; D017361:Viral Nonstructural Proteins; D007372:Interferons