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Journal of Virology, December 2005, p. 15417-15429, Vol. 79, No. 24
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.24.15417-15429.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

SOCS1 and SOCS3 Are Targeted by Hepatitis C Virus Core/gC1qR Ligation To Inhibit T-Cell Function

Zhi Qiang Yao,1 Stephen N. Waggoner,1 Michael W. Cruise,1 Caroline Hall,1 Xuefang Xie,1 David W. Oldach,2 and Young S. Hahn1*

Beirne Carter Center for Immunology Research, Department of Microbiology and Pathology, University of Virginia, Charlottesville, Virginia 22908,1 Institute of Human Virology, University of Maryland, Baltimore, Maryland 212012

Received 22 April 2005/ Accepted 22 September 2005

T cells play an important role in the control of hepatitis C virus (HCV) infection. We have previously demonstrated that the HCV core inhibits T-cell responses through interaction with gC1qR. We show here that core proteins from chronic and resolved HCV patients differ in sequence, gC1qR-binding ability, and T-cell inhibition. Specifically, chronic core isolates bind to gC1qR more efficiently and inhibit T-cell proliferation as well as gamma interferon (IFN-{gamma}) production more profoundly than resolved core isolates. This inhibition is mediated by the disruption of STAT phosphorylation through the induction of SOCS molecules. Silencing either SOCS1 or SOCS3 by small interfering RNA dramatically augments the production of IFN-{gamma} in T cells, thereby abrogating the inhibitory effect of core. Additionally, the ability of core proteins from patients with chronic infections to induce SOCS proteins and suppress STAT activation greatly exceeds that of core proteins from patients with resolved infections. These results suggest that the HCV core/gC1qR-induced T-cell dysfunction involves the induction of SOCS, a powerful inhibitor of cytokine signaling, which represents a novel mechanism by which a virus usurps the host machinery for persistence.

* Corresponding author. Mailing address: Beirne Carter Center for Immunology Research, Department of Microbiology and Pathology, University of Virginia, Charlottesville, VA 22908. Phone: (434) 924-1155. Fax: (434) 924-1221. E-mail: ysh5e{at}virginia.edu.

Journal of Virology, December 2005, p. 15417-15429, Vol. 79, No. 24
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.24.15417-15429.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Ye, Y., Hauns, K., Langland, J. O., Jacobs, B. L., Hogue, B. G. (2007). Mouse Hepatitis Coronavirus A59 Nucleocapsid Protein Is a Type I Interferon Antagonist. J. Virol. 81: 2554-2563 [Abstract] [Full Text]  
  • Lin, W., Kim, S. S., Yeung, E., Kamegaya, Y., Blackard, J. T., Kim, K. A., Holtzman, M. J., Chung, R. T. (2006). Hepatitis C Virus Core Protein Blocks Interferon Signaling by Interaction with the STAT1 SH2 Domain.. J. Virol. 80: 9226-9235 [Abstract] [Full Text]  


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