JAC Advance Access originally published online on September 18, 2009
Journal of Antimicrobial Chemotherapy 2009 64(5):945-948; doi:10.1093/jac/dkp328
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Original research |
Screening for hepatitis C virus non-nucleotide resistance mutations in treatment-naive women
1 Division of Digestive Diseases, University of Cincinnati College of Medicine, Cincinnati, OH, USA 2 Miriam Hospital and Department of Medicine, Brown University, Providence, RI, USA 3 Division of Reproductive Health, Centers for Disease Control and Prevention, Atlanta, GA, USA
Received 29 June 2009; returned 19 July 2009; revised 8 August 2009; accepted 12 August 2009
* Corresponding author. Tel: +1-513-558-4389; Fax: +1-513-558-1744; E-mail: jason.blackard{at}uc.edu
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.
Keywords: HCV , NS5B , C316Y