T细胞分化因子CBF-β在HIV-1 Vif形成的E3泛素化连接酶中的作用

作为重大传染性疾病之首的艾滋病病毒HIV-1，一直是世界病毒学领域研究的热点。HIV-1编码的Vif蛋白是病毒复制必不可少的因子，近几年在Nature等国际顶级杂志发表的有关它的文章已超过20篇。Vif蛋白与宿主细胞内CUL5、ElOB/C等蛋白形成E3连接酶，突破宿主天然防御因子APOBEC3的抗病毒作用。2012年申请者进一步完善了Vif蛋白的作用机制，发现和定义了T细胞分化因子CBF-β在病毒侵袭及复制过程中的重要调控作用，研究成果发表在Nature杂志。但是，在HIV感染过程中，CBF-β的具体作用以及Vif是否影响它作为转录调节因子的正常功能等等科学问题目前尚不清楚。本项目将进一步确定CBF-β在Vif形成的E3泛素连接酶和逃避宿主防御因子过程中的具体作用，确定HIV-1 Vif分子与CBF-β结合的功能区，对于合理设计针对新靶点的新型抑制剂具有重要的指导意义。

HIV-1 as a severe contagious disease has always been hotspots in the field of virology in the worldwide. Viral infectivity factor (Vif) encoded by HIV-1 is indispensable for the virus replication. Over 20 papers were published in the world-wide famous journal like Nature. HIV-1 Vif protein is able to neutralize the antiviral activity of natural defensive factor APOBEC3G by hijacking cellular factors Cullin5、ElonginB、ElonginC and forming E3 ubiquitination ligase. Based on the previous work, applier has clarified the mechanism of Vif protein in formation of E3 ubiquitination ligase, and identified T cell differentiation factor CBF-β is a novel key regulator in this course which was published in Nature in 2012. But as a novel factor, the role of CBF-β in the replication of HIV-1 and effect of Vif on its transcription regulation were still unknown. The project will futher determine the function of CBF-β in the E3 ligase hijacked by Vif and the interaction domains of Vif and CBF-β which will be helpful for designing a novel inhibitor targeting a novel attractive pharmacologic intervention against HIV-1.