Hepatitis C virus: immunosuppression by complement regulatory pathway.
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 Clq complement receptor, gC1qR, can bind to the HCV core. Clq is a ligand of gClqR and is involved in the early defense against viral infection as well as regulation of adaptive immune response. Similar to Clq, the HCV core can inhibit human T-lymphocyte proliferative response through its interaction with the gC1qR. It implicates that HCV core/gClqR-induced immune suppression may play a critical role in the establishment of persistent infection.
Yao
Z Q
ZQ
Beirne Carter Center for Immunology Research, University of Virginia, Charlottesville 22908, USA.
Ray
S
S
Eisen-Vandervelde
A
A
Waggoner
S
S
Hahn
Y S
YS
D000818:Animals; D002352:Carrier Proteins; D015922:Complement C1q / Q000276:immunology*; D016174:Hepacivirus / Q000276:immunology / Q000472:pathogenicity*; D019698:Hepatitis C, Chronic / Q000209:etiology*; D006801:Humans; D018960:Hyaluronan Receptors; D007108:Immune Tolerance; D008213:Lymphocyte Activation / Q000276:immunology; D008562:Membrane Glycoproteins; D024101:Mitochondrial Proteins; D011951:Receptors, Complement / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D014758:Viral Core Proteins / Q000276:immunology* / Q000494:pharmacology
C087299:C1QBP protein, human; D002352:Carrier Proteins; D018960:Hyaluronan Receptors; D008562:Membrane Glycoproteins; D024101:Mitochondrial Proteins; D011951:Receptors, Complement; D014758:Viral Core Proteins; C032402:complement 1q receptor; D015922:Complement C1q