BST2是最近发现具有广谱抑制病毒颗粒释放的宿主限制因子，其表达可以显著抑制HIV-1等病毒颗粒从感染细胞释放，而HIV-1病毒蛋白Vpu通过跨膜区与BST-2的相互作用，下调细胞BST-2，阻断其对病毒的抑制作用。阻断Vpu降解BST-2为抗HIV-1及其他病毒药物提供了一种新研发的思路。依据前期工作基础，我们拟建立检测BST-2与Vpu相互作用手段（生物发光共振能量转移，BRET），系统全面检测位于BST-2与Vpu跨膜区相互作用位点，找到具有关键作用的氨基酸。同时运用BRET检测体系，筛选可以干扰Vpu与BST-2相互作用，阻止其下调BST-2的小分子化合物。该项目的研究不仅可以找到位于BST-2与Vpu跨膜区相互作用关键氨基酸位点，找到干扰BST-2与Vpu相互作用小分子化合物，而且通过对小分子化合物筛选也可以明确两者的相互作用机制，为抗艾滋病药物研发提供新的思路和靶点。

The host restriction factor BST-2 was indentified to be responsible for the inhibition of enveloped virus release include HIV-1, and HIV-1 accessory protein Vpu can specific target it and efficiently antagonize this restriction. This complete process of Vpu counteracting BST-2 is based on the interaction between BST-2 and Vpu. Blocking Vpu mediated down-regulation of BST-2 is viewed as a new opportunity for developing anti-HIV drugs. Based on previous study in the interaction of BST-2 and Vpu, we plan to utilize Bioluminescence resonance energy transfer (BRET) approach to identify the key amino acids of the two transmembrane (TM) domains for their interaction. Next, we will utilized BRET approach to identify small molecules that antagonized HIV-1 Vpu function and restore the BST-2 cellular levels. In general, the achievement of the research work in the proposal will identify the critical amino acids of BST-2 and Vpu at transmembrane domains responsible for their interaction and discovery small molecules that influence the interaction between BST-2 and Vpu, can promote the basic study of Vpu mediated down-regulation BST-2, benefit the application for developing anti-HIV drugs.