艾滋病作为公认的世界性难题，迫切需要对其致病机理进行深入研究。cGAS-STING-TBK1作为新兴的信号通路，在抗病毒免疫应答中起着重要作用。我们前期发现，HIV-1的Vif蛋白通过宿主SHP-1与STING相互作用。然而，Vif-SHP-1-STING复合物调控固有免疫信号通路的具体机制及在HIV感染中的作用尚不清楚。已有结果表明，Vif不仅促进SHP-1与STING的结合，且通过抑制STING的Y162酪氨酸磷酸化，抑制其K337赖氨酸的K63泛素化，从而抑制了抗病毒信号通路的活化及I型干扰素的产生。本项目拟从分子和细胞水平深入研究Vif-SHP-1-STING相互作用的分子机制，进一步阐明Vif在HIV-1感染中的免疫抑制作用及免疫逃逸新机制。本研究结果将为感染免疫研究提供新的分子基础，更将为艾滋病的治疗以及相关药物的研发提供新的发展方向和药物靶标，具有潜在的应用前景和理论价值。

AIDS is a world-wide hard question, it is urgent to study its pathogenic mechanism. cGAS-STING-TBK1 axis is a new signal pathway and plays an important role in anti-viral immune response. Our previous results showed that Vif protein from HIV interact with host STING through SHP-1. Whether Vif regulate anti-viral signal pathways through this complex, the mechanism and its role in HIV infection is still unclear. Our previous experiments found that Vif enhanced the interaction of SHP-1 and STING, and inhibited its tyrosine phosphorylation at Y162 to inhibit it K63-linked ubiquitination at K337, and then inhibit anti-viral signal pathway and downstream type I interferon production. In this project, we will investigate the interaction mechanism of Vif-SHP-1-STING at molecular and cellular levels. We will also clarify the inhibitory and the immune evasion role of Vif during HIV infection. These results will provide a new molecular basis for infection immunity study and open a new way for the treatment of AIDS and the development of novel drugs, which has important application prospects and values.