人延伸因子EloBC在HIV-1感染过程中的调节作用及机制研究

HIV accessory protein Vif is crucial for HIV infection and proliferation in non-permission cells. Former studies have indicated that Vif interacts with a serious of human factors to induce proteasomal degradation of human anti-viral protein family, APOBEC. The interaction and mechanism between Vif and human factors is an area of focus. According to our previous study, the human elongation factor B and C are crucial for the function of Vif. More importantly, our result have displayed that there are un-identified new human factors involved in this process. Our study will focus on the identity of the new factors, the potential impression on Vif inducing A3G degradation, cells G2 arrest and on the HIV-1 infection and proliferation by the new factors through exogenous proteins expression, co-immunoprecipitation, MS, gene cloning, flow cytometry and gene operations, etc. Moreover, we will try to identify the crucial regions and amino acids for the new factor to interact with and affect on Vif. Our goal is to provide new target and details for the development of anti-viral strategy.

HIV的辅助蛋白Vif是病毒在特定靶细胞中感染增殖的必要因子。Vif蛋白在宿主细胞内结合一系列内源因子，诱导人抗病毒蛋白APOBEC家族成员的蛋白酶体降解，协助病毒抵抗宿主细胞的防御。Vif与宿主蛋白的相互作用和调节机制的研究一直以来是本领域关注的热点。本研究前期结果显示，在Vif与人延伸因子EloBC的相互作用过程中，还存在没有被鉴定出的细胞内因子参与其中。本研究将通过原核及真核细胞表达、免疫共沉淀、质谱检测、基因克隆、流式细胞术等技术鉴定新因子、验证其与Vif的相互作用、检测其过量表达和敲除对HIV-1 Vif功能的影响以及其对HIV-1病毒的感染性、病毒在靶细胞系中增殖的影响；并探索新因子与Vif相互作用的关键区域和关键位点。本项目通过深入探讨人延长因子EloBC与HIV-1辅助蛋白Vif的相互作用，为研发针对Vif蛋白功能的抗HIV药物提供全新机制和靶点，具有重要的研究意义。