Interaction between complement receptor gC1qR and hepatitis C virus core protein inhibits T-lymphocyte proliferation
David J. Kittlesen, … , Thomas J. Braciale, Young S. Hahn
David J. Kittlesen, … , Thomas J. Braciale, Young S. Hahn
Published November 15, 2000
Citation Information: J Clin Invest. 2000;106(10):1239-1249. https://doi.org/10.1172/JCI10323.
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Article

Interaction between complement receptor gC1qR and hepatitis C virus core protein inhibits T-lymphocyte proliferation

Abstract

Hepatitis C virus (HCV) is an important human pathogen that is remarkably efficient at establishing persistent infection. The HCV core protein is the first protein expressed during the early phase of HCV infection. Our previous work demonstrated that the HCV core protein suppresses host immune responses, including anti-viral cytotoxic T-lymphocyte responses in a murine model. To investigate the mechanism of HCV core-mediated immunosuppression, we searched for host proteins capable of associating with the core protein using a yeast two-hybrid system. Using the core protein as bait, we screened a human T cell–enriched expression library and identified a gene encoding the gC1q receptor (gC1qR). C1q is a ligand of gC1qR and is involved in the early host defense against infection. Like C1q, HCV core can inhibit T-cell proliferative responses in vitro. This core-induced anti–T-cell proliferation is reversed by addition of anti-gC1qR Ab in a T-cell proliferation assay. Furthermore, biochemical analysis of the interaction between core and gC1qR indicates that HCV core binds the region spanning amino acids 188 to 259 of gC1qR, a site distinct from the binding region of C1q. The inhibition of T-cell responsiveness by HCV core may have important implications for HCV persistence in humans.

Authors

David J. Kittlesen, Kimberly A. Chianese-Bullock, Zhi Qiang Yao, Thomas J. Braciale, Young S. Hahn

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Inhibition of T-lymphocyte proliferation by HCV core protein. (a) Effect...
Inhibition of T-lymphocyte proliferation by HCV core protein. (a) Effect of HCV core protein on T-cell proliferation. Standard one-way mixed lymphocyte reactions were performed in the presence of C1q (50 μg/ml), the indicated concentration of purified HCV core protein, or core buffer (control response). After 6 days of coculture, proliferation was measured as 18-hour 3(H)-thymidine incorporation. (b) Effect of HCV NS3 protein on T-cell proliferation. HCV NS3 protein was tested for its ability to modulate the proliferation of T lymphocytes as described above. (c) Effect of HCV core protein on conA-stimulated T-cell proliferation. MLR was performed in the presence of conA (2 μg/ml) and the indicated amount of HCV core protein or control protein, β-gal.