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

Hepatitis C virus (HCV) is an important human pathogen that is remarkably e fficient at establishing persistent infection. The HCV core protein is the first protein expressed during the early phase of HCV infection. Our previo us work demonstrated that the HCV core protein suppresses host immune respo nses, including anti-viral cytotoxic T-lymphocyte responses in a murine mod el. To investigate the mechanism of HCV core-mediated immunosuppression, we searched for host proteins capable of associating with the core protein us ing 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 t he gC1q receptor (gC1qR). C1q is a ligand of gC1qR and is involved in the e arly host defense against infection. Like Clq, HCV core can inhibit T-cell proliferative responses in vitro. This core-induced anti-T-cell proliferati on is reversed by addition of anti-gC1qR Ab in a T-cell proliferation assay . Furthermore, biochemical analysis of the interaction between core and gC1 qR indicates that HCV core binds the region spanning amino acids 188 to 259 of gC1qR, a site distinct From the binding region of Clq. The inhibition o f T-cell responsiveness by HCV core may have important implications for HCV persistence in humans.