This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Donlin, M. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Donlin, M. J.

 Previous Article  |  Next Article 

Journal of Virology, August 2007, p. 8211-8224, Vol. 81, No. 15
0022-538X/07/$08.00+0     doi:10.1128/JVI.00487-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Pretreatment Sequence Diversity Differences in the Full-Length Hepatitis C Virus Open Reading Frame Correlate with Early Response to Therapy{triangledown}

Maureen J. Donlin,1 Nathan A. Cannon,1 Ermei Yao,1,{dagger} Jia Li,4 Abdus Wahed,4 Milton W. Taylor,5 Steven H. Belle,4 Adrian M. Di Bisceglie,2,3 Rajeev Aurora,1 John E. Tavis,1,3* for the Virahep-C Study Group

Department of Molecular Microbiology and Immunology,1 Department of Internal Medicine,2 Saint Louis University Liver Center, Saint Louis University School of Medicine, 1402 S. Grand Blvd., Saint Louis, Missouri 63104,3 Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania,4 Department of Biology, Indiana University, Bloomington, Indiana5

Received 7 March 2007/ Accepted 11 May 2007

Pegylated alpha interferon and ribavirin therapy for hepatitis C virus (HCV) genotype 1 infection fails for half of Caucasian American patients (CA) and more often for African Americans (AA). The reasons for these low response rates are unknown. HCV is highly genetically variable, but it is unknown how this variability affects response to therapy. To assess effects of viral diversity on response to therapy, the complete pretreatment genotype 1 HCV open reading frame was sequenced using samples from 94 participants in the Virahep-C study. Sequences from patients with >3.5 log declines in viral RNA levels by day 28 (marked responders) were more variable than those from patients with declines of <1.4 log (poor responders) in NS3 and NS5A for genotype 1a and in core and NS3 for genotype 1b. These correlations remained when all T-cell epitopes were excluded, indicating that these differences were not due to differential immune selection. When the sequences were compared by race of the patients, higher diversity in CA patients was found in E2 and NS2 but only for genotype 1b. Core, NS3, and NS5A can block the action of alpha interferon in vitro; hence, these genetic patterns are consistent with multiple amino acid variations independently impairing the function of HCV proteins that counteract interferon responses in humans, resulting in HCV strains with variable sensitivity to therapy. No evidence was found for novel HCV strains in the AA population, implying that AA patients may be infected with a higher proportion of the same resistant strains that are found in CA patients.

* Corresponding author. Mailing address: Department of Molecular Microbiology and Immunology, Saint Louis University School of Medicine, 1402 S. Grand Blvd., Saint Louis, MO 63104. Phone: (314) 977-8893. Fax: (314) 977-8717. E-mail: tavisje{at}slu.edu

{triangledown} Published ahead of print on 23 May 2007.

{dagger} Present address: College of Medicine, University of Iowa, Iowa City, IA.

Journal of Virology, August 2007, p. 8211-8224, Vol. 81, No. 15
0022-538X/07/$08.00+0     doi:10.1128/JVI.00487-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Ford, D., Matsen, F. A., Stadler, T. (2009). A Method for Investigating Relative Timing Information on Phylogenetic Trees. Syst Biol 0: syp018v1-syp018 [Abstract] [Full Text]  
  • Fishman, S. L., Factor, S. H., Balestrieri, C., Fan, X., DiBisceglie, A. M., Desai, S. M., Benson, G., Branch, A. D. (2009). Mutations in the Hepatitis C Virus core Gene Are Associated with Advanced Liver Disease and Hepatocellular Carcinoma. Clin. Cancer Res. 15: 3205-3213 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»