Direct Binding of Hepatitis C Virus Core to gC1qR on CD4+ and CD8+ T Cells Leads to Impaired Activation of Lck and Akt

AUTOR(ES)

Yao, Zhi Qiang

FONTE

American Society for Microbiology

RESUMO

Complement plays a pivotal role in the regulation of innate and adaptive immunity. It has been shown that the binding of C1q, a natural ligand of gC1qR, on T cells inhibits their proliferation. Here, we demonstrate that direct binding of the hepatitis C virus (HCV) core to gC1qR on T cells leads to impaired Lck/Akt activation and T-cell function. The HCV core associates with the surface of T cells specifically via gC1qR, as this binding is inhibited by the addition of either anti-gC1qR antibody or soluble gC1qR. The binding affinity constant of core protein for gC1qR, as determined by BIAcore analysis, is 3.8 × 10−7 M. The specificity of the HCV core-gC1qR interaction is confirmed by reduced core binding on Molt-4 T cells treated with gC1qR-silencing small interfering RNA and enhanced core binding on GPC-16 guinea pig cells transfected with human gC1qR. Interestingly, gC1qR is expressed at higher levels on CD8+ than on CD4+ T cells, resulting in more severe core-induced suppression of the CD8+-T-cell population. Importantly, T-cell receptor-mediated activation of the Src kinases Lck and ZAP-70 but not Fyn and the phosphorylation of Akt are impaired by the HCV core, suggesting that it inhibits the very early events of T-cell activation.

Documentos Relacionados

• Interaction between complement receptor gC1qR and hepatitis C virus core protein inhibits T-lymphocyte proliferation
• In Vitro and In Vivo Interactions between the Hepatitis B Virus Protein P22 and the Cellular Protein gC1qR
• Identification of a gC1q-binding protein (gC1q-R) on the surface of human neutrophils. Subcellular localization and binding properties in comparison with the cC1q-R.
• Human CD4+ and CD8+ T lymphocytes are both cytotoxic to Toxoplasma gondii-infected cells.
• Role of CD4+ and CD8+ T cells in murine resistance to street rabies virus.