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 Chambers, T. J.
Right arrow Articles by DiBisceglie, A. M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Chambers, T. J.
Right arrow Articles by DiBisceglie, A. M.

 Previous Article  |  Next Article 

Journal of Virology, March 2005, p. 3071-3083, Vol. 79, No. 5
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.5.3071-3083.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Quasispecies Heterogeneity within the E1/E2 Region as a Pretreatment Variable during Pegylated Interferon Therapy of Chronic Hepatitis C Virus Infection

Thomas J. Chambers,1* Xiaofeng Fan,2 Deborah A. Droll,1 Edgardo Hembrador,1 Tiffany Slater,1 Michael W. Nickells,1 Lynn B. Dustin,3 and Adrian M. DiBisceglie2

Department of Molecular Microbiology and Immunology, St. Louis University School of Medicine,1 Department of Medicine, Division of Gastroenterology and Hepatology, St. Louis University Health Sciences Center, St. Louis, Missouri,2 Center for the Study of Hepatitis C, The Rockefeller University, New York, New York3

Received 7 July 2004/ Accepted 18 October 2004

A series of 29 patients undergoing treatment for chronic hepatitis C virus (HCV) genotype 1 infection with pegylated alpha-2a interferon plus ribavirin were studied for patterns of response to antiviral therapy and viral quasispecies evolution. All patients were treatment naive and had chronic inflammation and fibrosis on biopsy. As part of an analysis of pretreatment variables that might affect the outcome of treatment, genetic heterogeneity within the viral E1-E2 glycoprotein region (nucleotides 851 to 2280) was assessed by sequencing 10 to 15 quasispecies clones per patient from serum-derived PCR products. Genetic parameters were examined with respect to response to therapy based on serum viral RNA loads at 12 weeks (early viral response) and at 24 weeks posttreatment (sustained viral response). Nucleotide and amino acid quasispecies complexities of the hypervariable region 1 (HVR-1) were less in the responder group in comparison to the nonresponder group at 12 weeks, and genetic diversity was also less both within and outside of the HVR-1, with the difference being most pronounced for the non-HVR-1 region of E2. However, these genetic parameters did not distinguish responders from nonresponders for sustained viral responses. Follow-up studies of genetic heterogeneity based on the HVR-1 in selected responders and nonresponders while on therapy revealed greater evolutionary drift in the responder subgroup. The pretreatment population sequences for the NS5A interferon sensitivity determinant region were also analyzed for all patients, but no correlations were found between treatment response and any distinct genetic markers. These findings support previous studies indicating a high level of genetic heterogeneity among chronically infected HCV patients. One interpretation of these data is that early viral responses are governed to some extent by viral factors, whereas sustained responses may be more influenced by host factors, in addition to effects of viral complexity and diversity.

* Corresponding author. Mailing address: 1402 South Grand Blvd., St. Louis, MO 63104. Phone: (314) 977-8711. Fax: (314) 977-8717. E-mail: chambetj{at}slu.edu.

Journal of Virology, March 2005, p. 3071-3083, Vol. 79, No. 5
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.5.3071-3083.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Xu, Z., Fan, X., Xu, Y., Di Bisceglie, A. M. (2008). Comparative Analysis of Nearly Full-Length Hepatitis C Virus Quasispecies from Patients Experiencing Viral Breakthrough during Antiviral Therapy: Clustered Mutations in Three Functional Genes, E2, NS2, and NS5a. J. Virol. 82: 9417-9424 [Abstract] [Full Text]  
  • Wohnsland, A., Hofmann, W. P., Sarrazin, C. (2007). Viral Determinants of Resistance to Treatment in Patients with Hepatitis C. Clin. Microbiol. Rev. 20: 23-38 [Abstract] [Full Text]  
  • Wrobel, B., Torres-Puente, M., Jimenez, N., Bracho, M. A., Garcia-Robles, I., Moya, A., Gonzalez-Candelas, F. (2006). Analysis of the Overdispersed Clock in the Short-Term Evolution of Hepatitis C Virus: Using the E1/E2 Gene Sequences to Infer Infection Dates in a Single Source Outbreak. Mol Biol Evol 23: 1242-1253 [Abstract] [Full Text]  
  • Alfonso, V., Mbayed, V. A., Sookoian, S., Campos, R. H. (2005). Intra-host evolutionary dynamics of hepatitis C virus E2 in treated patients. J. Gen. Virol. 86: 2781-2786 [Abstract] [Full Text]  
  • Butera, D., Marukian, S., Iwamaye, A. E., Hembrador, E., Chambers, T. J., Di Bisceglie, A. M., Charles, E. D., Talal, A. H., Jacobson, I. M., Rice, C. M., Dustin, L. B. (2005). Plasma chemokine levels correlate with the outcome of antiviral therapy in patients with hepatitis C. Blood 106: 1175-1182 [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»