Hepatitis C Virus: Immunosuppression by Complement Regulatory Pathway

Abstract

Hepatitis C virus (HCV) infection in humans is almost invariably associated with viral persistence and chronic hepatitis. HCV-induced chronic hepatitis is a major risk factor for the development of hepatocellular carcinoma. The high incidence of HCV persistence suggests that this virus has evolved one or more mechanisms to evade and possibly suppress host immune responses. To understand the mechanism(s) involved in the establishment of HCV persistence, we have identified an HCV core protein as an immunomodulatory molecule to suppress host immune response. We have further determined a molecular mechanism of HCV core-mediated immune suppression by searching for a potential host protein(s) capable of associating with the HCV core protein. Interestingly, the C1q complement receptor, gC1qR, can bind to the HCV core. C1q is a ligand of gC1qR and is involved in the early defense against viral infection as well as regulation of adaptive immune response. Similar to C1q, the HCV core can inhibit human T-lymphocyte proliferative response through its interaction with the gC1qR. It implicates that HCV core/gC1qR-induced immune suppression may play a critical role in the establishment of persistent infection.