Journal article
Screening for hepatitis C virus non-nucleotide resistance mutations in treatment-naive women
Journal of antimicrobial chemotherapy, Vol.64(5), pp.945-948
11/01/2009
DOI: 10.1093/jac/dkp328
PMCID: PMC2766823
PMID: 19767319
Abstract
Objectives Hepatitis C virus (HCV) non-nucleoside inhibitors (NNIs) target the viral RNA-dependent RNA polymerase encoded by the NS5B gene. Several NNIs share a similar allosteric binding site, and their antiviral efficacy is attenuated by a cysteine-to-tyrosine mutation at amino acid 316 (C316Y). In the current study, we assessed NS5B resistance mutations in treatment-naive individuals from a prospective natural history study of viral infections in women. Methods Partial NS5B sequences from HCV-positive women were amplified by RT–PCR. Additionally, subcloning was performed to evaluate intrapatient variability in selected samples. Results HCV NS5B genotypes were 45 genotype 1a (57.0%), 11 genotype 1b (13.9%), 5 genotype 2a (6.3%), 3 genotype 2b (3.8%), 9 genotype 3a (11.4%) and 6 genotype 4a (7.6%). One HCV genotype 1a-infected patient was found to have the C316Y mutation (1.3%). Clonal analysis further revealed that all NS5B sequences from this individual—representing three serum samples collected 4 years apart—contained the C316Y mutation. In contrast, the S282T resistance mutation was not found in any samples. Conclusions The C316Y polymerase resistance mutation was found in 1.3% of samples from HCV-infected women. The presence of this mutation over time suggests significant replicative fitness of this variant and has implications for development of new specifically targeted antiviral therapies against HCV (STAT-C) targeting this region.
Details
- Title: Subtitle
- Screening for hepatitis C virus non-nucleotide resistance mutations in treatment-naive women
- Creators
- Peter D. Dryer - University of CincinnatiBerkeley N. Limketkai - University of CincinnatiChristina M. Martin - University of CincinnatiGang Ma - University of CincinnatiKenneth E. Sherman - University of CincinnatiLynn E. Taylor - Brown UniversityKenneth H. Mayer - Brown UniversityDenise J. Jamieson - Centers for Disease Control and PreventionJason T. Blackard - University of Cincinnati
- Resource Type
- Journal article
- Publication Details
- Journal of antimicrobial chemotherapy, Vol.64(5), pp.945-948
- Publisher
- Oxford University Press
- DOI
- 10.1093/jac/dkp328
- PMID
- 19767319
- PMCID
- PMC2766823
- ISSN
- 0305-7453
- eISSN
- 1460-2091
- Language
- English
- Date published
- 11/01/2009
- Academic Unit
- Obstetrics and Gynecology; VPMA - Administration
- Record Identifier
- 9984446440402771
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