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 Wyatt, C. A.
Right arrow Articles by Prince, A. M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Wyatt, C. A.
Right arrow Articles by Prince, A. M.

 Previous Article  |  Next Article 

J Virol, March 1998, p. 1725-1730, Vol. 72, No. 3
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Immunity in Chimpanzees Chronically Infected with Hepatitis C Virus: Role of Minor Quasispecies in Reinfection

Colby A. Wyatt, Linda Andrus, Betsy Brotman, Fannie Huang, Dong-Hun Lee, and Alfred M. Prince*

Laboratories of Virology and Parasitology and of Microchemistry, The Lindsley F. Kimball Research Institute of the New York Blood Center, New York, New York 10021

Received 30 January 1997/Accepted 18 November 1997

We have previously reported that chimpanzees chronically infected with hepatitis C virus (HCV) could be reinfected, even with the original infecting strain. In this study we tested the hypothesis that this might reflect the presence of minor quasispecies to which there was little or no immunity. To evaluate this hypothesis, we sequenced multiple clones taken at intervals after primary infection and rechallenge from four chronically infected chimpanzees. The inoculum used in these studies (HCV-H, genotype 1a) revealed 17 separate variants among 46 clones sequenced. Following challenge, each of the four challenged animals showed marked alterations of their quasispecies distribution. The new variants, which appeared 1 to 6 weeks after challenge, were either identical to or closely resembled variants present in the challenge inoculum. These results, paralleled by an increase in viremia in some of the challenged animals, suggest that quasispecies in the challenge inoculum were responsible for signs of reinfection and that there was little immunity. However, the newly emerged quasispecies completely took over infection in only one animal. In the remaining three chimpanzees the prechallenge quasispecies were able to persist. The natural evolution of infection within chimpanzees resulted in variants able to compete with the inoculum variants. Whether through reexposure or the natural progression of infection, newly emerged quasispecies are likely to play a role in the pathogenesis of chronic HCV infection.

* Corresponding author. Mailing address: The New York Blood Center, 310 E. 67th St., New York, NY 10021. Phone: (212) 570-3279. Fax: (212) 570-3180. E-mail: aprince{at}NYBC.org.




This article has been cited by other articles:

  • Nainan, O. V., Lu, L., Gao, F.-X., Meeks, E., Robertson, B. H., Margolis, H. S. (2006). Selective transmission of hepatitis C virus genotypes and quasispecies in humans and experimentally infected chimpanzees. J. Gen. Virol. 87: 83-91 [Abstract] [Full Text]  
  • Cabot, B., Martell, M., Esteban, J. I., Piron, M., Otero, T., Esteban, R., Guardia, J., Gomez, J. (2001). Longitudinal Evaluation of the Structure of Replicating and Circulating Hepatitis C Virus Quasispecies in Nonprogressive Chronic Hepatitis C Patients. J. Virol. 75: 12005-12013 [Abstract] [Full Text]  
  • Lauer, G. M., Walker, B. D. (2001). Hepatitis C Virus Infection. NEJM 345: 41-52 [Full Text]  
  • Racanelli, V., Sansonno, D., Piccoli, C., D'Amore, F. P., Tucci, F. A., Dammacco, F. (2001). Molecular Characterization of B Cell Clonal Expansions in the Liver of Chronically Hepatitis C Virus-Infected Patients. J. Immunol. 167: 21-29 [Abstract] [Full Text]  
  • Lai, V. C. H., Zhong, W., Skelton, A., Ingravallo, P., Vassilev, V., Donis, R. O., Hong, Z., Lau, J. Y. N. (2000). Generation and Characterization of a Hepatitis C Virus NS3 Protease-Dependent Bovine Viral Diarrhea Virus. J. Virol. 74: 6339-6347 [Abstract] [Full Text]  
  • Butkiewicz, N., Yao, N., Zhong, W., Wright-Minogue, J., Ingravallo, P., Zhang, R., Durkin, J., Standring, D. N., Baroudy, B. M., Sangar, D. V., Lemon, S. M., Lau, J. Y. N., Hong, Z. (2000). Virus-Specific Cofactor Requirement and Chimeric Hepatitis C Virus/GB Virus B Nonstructural Protein 3. J. Virol. 74: 4291-4301 [Abstract] [Full Text]  
  • Ruiz-Jarabo, C. M., Arias, A., Baranowski, E., Escarmís, C., Domingo, E. (2000). Memory in Viral Quasispecies. J. Virol. 74: 3543-3547 [Abstract] [Full Text]  
  • Ray, S. C., Mao, Q., Lanford, R. E., Bassett, S., Laeyendecker, O., Wang, Y.-M., Thomas, D. L. (2000). Hypervariable Region 1 Sequence Stability during Hepatitis C Virus Replication in Chimpanzees. J. Virol. 74: 3058-3066 [Abstract] [Full Text]  
  • Allain, J.-P., Dong, Y., Vandamme, A.-M., Moulton, V., Salemi, M. (2000). Evolutionary Rate and Genetic Drift of Hepatitis C Virus Are Not Correlated with the Host Immune Response: Studies of Infected Donor-Recipient Clusters. J. Virol. 74: 2541-2549 [Abstract] [Full Text]  
  • Pawlotsky, J.-M., Germanidis, G., Frainais, P.-O., Bouvier, M., Soulier, A., Pellerin, M., Dhumeaux, D. (1999). Evolution of the Hepatitis C Virus Second Envelope Protein Hypervariable Region in Chronically Infected Patients Receiving Alpha Interferon Therapy. J. Virol. 73: 6490-6499 [Abstract] [Full Text]  
  • Major, M. E., Mihalik, K., Fernandez, J., Seidman, J., Kleiner, D., Kolykhalov, A. A., Rice, C. M., Feinstone, S. M. (1999). Long-Term Follow-Up of Chimpanzees Inoculated with the First Infectious Clone for Hepatitis C Virus. J. Virol. 73: 3317-3325 [Abstract] [Full Text]  
  • Ferrari, E., Wright-Minogue, J., Fang, J. W. S., Baroudy, B. M., Lau, J. Y. N., Hong, Z. (1999). Characterization of Soluble Hepatitis C Virus RNA-Dependent RNA Polymerase Expressed in Escherichia coli. J. Virol. 73: 1649-1654 [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»