title: gC1qR expression in chimpanzees with resolved and chronic infection: potential role of HCV core/gC1qR-mediated T cell suppression in the outcome of HCV infection.
abstract: Chimpanzee is a unique animal model for HCV infection, in which about 50% of infections resolve spontaneously. It has been reported that the magnitude of T cell responses to HCV core in recovered chimpanzees is greater than that in chronically infected ones. However, the mechanism(s) by which the chimpanzees with resolved infection overcome core-mediated immunosuppression remains unknown. In this study, we examined the effect of HCV core on T cell responsiveness in chimpanzees with resolved and chronic HCV infection. We found that core protein strongly inhibited T cell activation and proliferation in chimpanzees with chronic infection, while this inhibition was limited in chimpanzees with resolved infection. Notably, the level of gC1qR, as well as the binding of core protein, on the surface of T cells was lower in recovered chimpanzees when compared to chimpanzees with chronic HCV infection. Intriguingly, the observed differences in gC1qR expression levels and susceptibility to core-induced suppression amongst HCV-chronically infected and recovered chimpanzees were observed prior to HCV challenge, suggesting a possible genetic determination of the outcome of infection. These findings suggest that gC1qR expression on the surface of T cells is crucial for HCV core-mediated T cell suppression and viral clearance, and that represents a novel mechanism by which a virus usurps host machinery for persistence.
authors.affiliation: Department of Microbiology and Pathology, Beirne Carter Center for Immunology Research, University of Virginia, Charlottesville, VA 22908, USA.
authors.forename: Zhi Qiang
authors.initials: ZQ
authors.lastname: Yao
authors.forename: Mohamed Tarek
authors.initials: MT
authors.lastname: Shata
authors.forename: Nancy
authors.initials: N
authors.lastname: Tricoche
authors.forename: Mei Mei
authors.initials: MM
authors.lastname: Shan
authors.forename: Betsy
authors.initials: B
authors.lastname: Brotman
authors.forename: Wolfram
authors.initials: W
authors.lastname: Pfahler
authors.forename: Young S
authors.initials: YS
authors.lastname: Hahn
authors.forename: Alfred M
authors.initials: AM
authors.lastname: Prince
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002452:Cell Count; D049109:Cell Proliferation; D004195:Disease Models, Animal; D004198:Disease Susceptibility; D015870:Gene Expression; D016174:Hepacivirus / Q000472:pathogenicity*; D019698:Hepatitis C, Chronic / Q000276:immunology*; D007108:Immune Tolerance; D008213:Lymphocyte Activation; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000235:genetics; D002679:Pan troglodytes; D011485:Protein Binding; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D011951:Receptors, Complement / Q000096:biosynthesis* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology*; D014758:Viral Core Proteins / Q000276:immunology*
chemical_list: D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D011951:Receptors, Complement; D014758:Viral Core Proteins; C032402:complement 1q receptor; C069130:nucleocapsid protein, Hepatitis C virus