COMPARISON OF FULL-LENGTH SEQUENCES OF INTERFERON-SENSITIVE AND RESISTANT HEPATITIS-C VIRUS 1B - SENSITIVITY TO INTERFERON IS CONFERRED BY AMINO-ACID SUBSTITUTIONS IN THE NS5A REGION

被引:550
作者
ENOMOTO, N
SAKUMA, I
ASAHINA, Y
KUROSAKI, M
MURAKAMI, T
YAMAMOTO, C
IZUMI, N
MARUMO, F
SATO, C
机构
[1] TOKYO MED & DENT UNIV, FAC MED, DEPT INTERNAL MED 2, BUNKYO KU, TOKYO 113, JAPAN
[2] TOKYO MED & DENT UNIV, FAC MED, DIV HLTH SCI, BUNKYO KU, TOKYO 113, JAPAN
[3] MUSASHINO RED CROSS HOSP, DEPT INTERNAL MED, MUSASHINO, TOKYO 180, JAPAN
关键词
CHRONIC ACTIVE HEPATITIS; INTERFERON SENSITIVITY DETERMINING REGION; POLYMERASE CHAIN REACTION; QUASI-SPECIES; SINGLE STRAND CONFORMATION;
D O I
10.1172/JCI118025
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
We have previously demonstrated that sensitivity to interferon is different among hepatitis C virus (HCV) quasispecies simultaneously detected in same individuals and that interferon-resistant HCV quasispecies are selected during the treatment, To determine the genetic basis of their resistance to interferon, HCV genotype-1b was obtained from serum of three patients before and during interferon therapy, and their full-length nucleotide and deduced amino acid sequences were determined, Comparison of the pairs of interferon-resistant and interferon-sensitive HCV isolates in respective individuals demonstrated clusters of amino acid differences in the COOH-terminal half of the NS5A region (codon 2154-2383), which contained a common unique amino acid difference at codon 2218, Additional sequence data of the COOH-terminal half of the NS5A region obtained from six interferon-resistant and nine interferon-sensitive HCV confirmed the exclusive existence of missense mutations in a 40 amino acid stretch of the NS5A region around codon 2218 (from codon 2209 to 2248) in interferon-sensitive HCV, On the other hand, this region of interferon-resistant HCV was identical to that of prototype HCV genotype-1b (HCV-J, HCV-JTa, or HC-J4), We designated this region as the interferon sensitivity determining region, Thus, HCV genotype-lb with the prototype interferon sensitivity determining region appears to be interferon-resistant strains, The specific nature of these mutations might make it possible to predict prognostic effects of interferon treatment.
引用
收藏
页码:224 / 230
页数:7
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