HIV/SIV具有多个特异性非结构蛋白，它们在病毒感染的不同时期发挥重要作用。其中Vpx由项目申请人所在团队带头人首先鉴定，它存在于HIV-2病毒和部分灵长类动物的SIV病毒中。研究表明，Vpx在DC细胞和巨噬细胞中利用E3泛素化连接酶特异性降解宿主体内重要的抗病毒因子SAMHD1，促进病毒的复制。近期我们团队发现，降解SAMHD1可能不是Vpx拮抗宿主免疫反应的唯一功能。本项目旨在揭示Vpx具有调控宿主天然免疫反应的能力，它通过抑制NF-κB信号通路的激活，进而调控通路下游抗病毒因子的转录表达。本项目将在人原代细胞中检测Vpx对于病毒感染进程的促进作用，筛选Vpx在天然免疫通路中调控的靶蛋白，阐明Vpx的分子机制和生物学意义。本项研究有望首次揭示Vpx拮抗天然免疫反应的新功能，为设计和研发抗HIV药物提供理论基础。

HIV/SIV has several specific non-structural proteins, which play an important role in different stages of virus infection. The Vpx was first identified by the team leader of the project applicant. It exists in HIV-2 virus and some of primates SIV viruses. Studies have shown that Vpx specifically degrades SAMHD1, an important antiviral factor in the host, by using E3 ubiquitin ligase in DC cells and macrophages, and promotes virus replication. Recently, our team found that degradation of SAMHD1 might not be the only function of Vpx in antagonizing host immune response. This project aims to reveal that Vpx has the ability to regulate the host innate immune response by inhibiting the activation of NF-κB signaling pathway, and then regulating the transcriptional expression of antiviral factors downstream of the NF-κB pathway. This project will detect the role of Vpx in promoting the process of virus infection in human primary cells, screen target proteins regulated by Vpx in innate immune pathways, and elucidate the molecular mechanism and biological significance of Vpx. The study is expected to be the first time to reveal the function of Vpx to antagonize innate immune response and provide a theoretical basis for the development and design of new targets for anti-HIV drugs.