title: 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.
abstract: 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.
authors.affiliation: Department of Internal Medicine, Division of Gastroenterology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Kazumasa
authors.initials: K
authors.lastname: Watanabe
authors.forename: Kentaro
authors.initials: K
authors.lastname: Yoshioka
authors.forename: Motoyoshi
authors.initials: M
authors.lastname: Yano
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Ishigami
authors.forename: Koji
authors.initials: K
authors.lastname: Ukai
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ito
authors.forename: Fumiyuki
authors.initials: F
authors.lastname: Miyata
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Mizutani
authors.forename: Hidemi
authors.initials: H
authors.lastname: Goto
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000145:classification / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D006526:Hepatitis C / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D007372:Interferons / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D010802:Phylogeny; D017422:Sequence Analysis, DNA; D016896:Treatment Outcome; D019562:Viral Load; D017361:Viral Nonstructural Proteins / Q000737:chemistry / Q000235:genetics; D012324:RNA-Dependent RNA Polymerase
chemical_list: D000998:Antiviral Agents; D007372:Interferons; D017361:Viral Nonstructural Proteins; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase