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Mutations in the nonstructural region 5B of hepatitis C virus genotype 1b: Their relation to viral load, response to interferon, and the nonstructural region 5A
Author(s) -
Watanabe Kazumasa,
Yoshioka Kentaro,
Yano Motoyoshi,
Ishigami Masatoshi,
Ukai Koji,
Ito Hiroshi,
Miyata Fumiyuki,
Mizutani Tetsuya,
Goto Hidemi
Publication year - 2005
Publication title -
journal of medical virology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.782
H-Index - 121
eISSN - 1096-9071
pISSN - 0146-6615
DOI - 10.1002/jmv.20301
Subject(s) - ns5b , ns5a , virology , biology , viral load , interferon , hepatitis c virus , virus , viral replication , mutation , hepacivirus , genetics , gene
The nonstructural 5B (NS5B) protein of hepatitis C virus possesses RNA‐dependent RNA polymerase activity and plays an essential role in viral replication. The mutations in NS5B were determined and the correlation with viral load and response to interferon (IFN) were assessed. The entire NS5B region in 33 patients and its thumb domain in 62 patients was sequenced. The number of amino acid substitutions in the NS5B protein, that in thumb domain and the substitution at aa 389 was correlated with viral load and the response to IFN. Multivariate analysis selected only mutation in IFN sensitivity determining region (ISDR) as a factor associated with the viral load and response to IFN. The number of substitutions in the thumb domain and the substitution at aa 389 correlated with the number of substitutions in the ISDR. These results suggest that mutations in NS5B, especially in the thumb domain and at aa 389, have an important effect on viral load and the response to IFN, although they were dependent on mutations in ISDR. Further studies on the relationship between NS5B and NS5A (ISDR) are necessary to elucidate the mechanism of the correlation with viral load and the response to IFN. J. Med. Virol. 75:504–512, 2005. © 2005 Wiley‐Liss, Inc.