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Title: gC1qR expression in chimpanzees with resolved and chronic infection: Potential role of HCV core/gC1qR-mediated T cell suppression in the outcome of HCV infection

Abstract

Chimpanzee is a unique animal model for HCV infection, in which about 50% of infections resolve spontaneously. It has been reported that the magnitude of T cell responses to HCV core in recovered chimpanzees is greater than that in chronically infected ones. However, the mechanism(s) by which the chimpanzees with resolved infection overcome core-mediated immunosuppression remains unknown. In this study, we examined the effect of HCV core on T cell responsiveness in chimpanzees with resolved and chronic HCV infection. We found that core protein strongly inhibited T cell activation and proliferation in chimpanzees with chronic infection, while this inhibition was limited in chimpanzees with resolved infection. Notably, the level of gC1qR, as well as the binding of core protein, on the surface of T cells was lower in recovered chimpanzees when compared to chimpanzees with chronic HCV infection. Intriguingly, the observed differences in gC1qR expression levels and susceptibility to core-induced suppression amongst HCV-chronically infected and recovered chimpanzees were observed prior to HCV challenge, suggesting a possible genetic determination of the outcome of infection. These findings suggest that gC1qR expression on the surface of T cells is crucial for HCV core-mediated T cell suppression and viral clearance, and that represents amore » novel mechanism by which a virus usurps host machinery for persistence.« less

Authors:
 [1];  [2];  [3];  [3];  [3];  [3];  [4];  [3]
  1. Department of Microbiology and Pathology, Beirne Carter Center for Immunology Research, University of Virginia, Charlottesville, VA 22908 (United States)
  2. Viral Immunology Laboratory, Division of Digestive Diseases, Department of Internal Medicine, University of Cincinnati Medical Center Cincinnati, OH 45267 (United States)
  3. Laboratory of Virology, Lindsley F. Kimball Research Institute, New York Blood Center, NY 10021 (United States)
  4. Department of Microbiology and Pathology, Beirne Carter Center for Immunology Research, University of Virginia, Charlottesville, VA 22908 (United States). E-mail: ysh5e@virginia.edu
Publication Date:
OSTI Identifier:
20779467
Resource Type:
Journal Article
Resource Relation:
Journal Name: Virology; Journal Volume: 346; Journal Issue: 2; Other Information: DOI: 10.1016/j.virol.2005.11.020; PII: S0042-6822(05)00768-3; Copyright (c) 2005 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; CELL PROLIFERATION; IMMUNOSUPPRESSION; INHIBITION; PROTEINS; VIRUSES

Citation Formats

Yao Zhiqang, Shata, Mohamed Tarek, Tricoche, Nancy, Shan, M.M., Brotman, Betsy, Pfahler, Wolfram, Hahn, Young S., and Prince, Alfred M. gC1qR expression in chimpanzees with resolved and chronic infection: Potential role of HCV core/gC1qR-mediated T cell suppression in the outcome of HCV infection. United States: N. p., 2006. Web. doi:10.1016/J.VIROL.2005.1.
Yao Zhiqang, Shata, Mohamed Tarek, Tricoche, Nancy, Shan, M.M., Brotman, Betsy, Pfahler, Wolfram, Hahn, Young S., & Prince, Alfred M. gC1qR expression in chimpanzees with resolved and chronic infection: Potential role of HCV core/gC1qR-mediated T cell suppression in the outcome of HCV infection. United States. doi:10.1016/J.VIROL.2005.1.
Yao Zhiqang, Shata, Mohamed Tarek, Tricoche, Nancy, Shan, M.M., Brotman, Betsy, Pfahler, Wolfram, Hahn, Young S., and Prince, Alfred M. Wed . "gC1qR expression in chimpanzees with resolved and chronic infection: Potential role of HCV core/gC1qR-mediated T cell suppression in the outcome of HCV infection". United States. doi:10.1016/J.VIROL.2005.1.
@article{osti_20779467,
title = {gC1qR expression in chimpanzees with resolved and chronic infection: Potential role of HCV core/gC1qR-mediated T cell suppression in the outcome of HCV infection},
author = {Yao Zhiqang and Shata, Mohamed Tarek and Tricoche, Nancy and Shan, M.M. and Brotman, Betsy and Pfahler, Wolfram and Hahn, Young S. and Prince, Alfred M.},
abstractNote = {Chimpanzee is a unique animal model for HCV infection, in which about 50% of infections resolve spontaneously. It has been reported that the magnitude of T cell responses to HCV core in recovered chimpanzees is greater than that in chronically infected ones. However, the mechanism(s) by which the chimpanzees with resolved infection overcome core-mediated immunosuppression remains unknown. In this study, we examined the effect of HCV core on T cell responsiveness in chimpanzees with resolved and chronic HCV infection. We found that core protein strongly inhibited T cell activation and proliferation in chimpanzees with chronic infection, while this inhibition was limited in chimpanzees with resolved infection. Notably, the level of gC1qR, as well as the binding of core protein, on the surface of T cells was lower in recovered chimpanzees when compared to chimpanzees with chronic HCV infection. Intriguingly, the observed differences in gC1qR expression levels and susceptibility to core-induced suppression amongst HCV-chronically infected and recovered chimpanzees were observed prior to HCV challenge, suggesting a possible genetic determination of the outcome of infection. These findings suggest that gC1qR expression on the surface of T cells is crucial for HCV core-mediated T cell suppression and viral clearance, and that represents a novel mechanism by which a virus usurps host machinery for persistence.},
doi = {10.1016/J.VIROL.2005.1},
journal = {Virology},
number = 2,
volume = 346,
place = {United States},
year = {Wed Mar 15 00:00:00 EST 2006},
month = {Wed Mar 15 00:00:00 EST 2006}
}
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