HIV-1宿主限制因子BST-2和拮抗蛋白Vpu的相互作用研究

The recent identified host restriction factor BST-2 efficiently inhibits the release of HIV-1 virus and lead to the blockage of the virus proliferation. The viral protein Vpu, an accessory protein of HIV-1, is able to down-regulate BST-2 at the cell surface, thus promoting the release of the virus. The interaction between the transmembrane domain (TMD) of Vpu and BST-2 is critical to the Vpu-mediated downregulation of BST-2. Based on our previous studies in the interaction of BST-2 and Vpu, we plan to combine the multiple methods from molecular modeling, chemical biology, bioassay and virology to optimize the binding mode of the TMD of BST-2 and Vpu. Next, we will perform the rational molecular design based the binding mode. The mechanism of the downregulation of BST-2 will be further investigated by the obtained active molecule. In general, the achievement of the research work in the proposal will promote the basic study of the innate immune system, and will benefit the application of the novel host restriction factor BST-2 on the anti-virus drug development for HIV-1 and other enveloped virus.

BST-2为新近发现的一种HIV-1宿主限制因子，可以有效抑制HIV-1病毒的释放，进而阻断病毒的复制。 HIV-1编码的Vpu蛋白可以下调细胞表面的BST-2，保证病毒的正常释放。Vpu 跨膜区与BST-2跨膜区的相互作用是Vpu对BST-2拮抗作用的关键。依据前期的工作基础，本申请研究拟以分子病毒学为基础，结合分子模拟、化学生物学及生物分析等技术手段，优化Vpu和BST-2跨膜区结合模型，在此基础上进行活性分子设计，进而利用所得活性分子进行Vpu下调细胞表面BST-2分子机制研究。该项目的开展不仅将推动宿主固有免疫系统基础研究的深入，而且为应用宿主限制因子BST-2防治HIV-1和其他包膜病毒感染为方向的药物研发奠定基础。

BST-2为新近发现的一种HIV-1宿主限制因子，可以有效抑制HIV-1病毒的释放，进而阻断病毒的复制。 HIV-1编码的Vpu蛋白可以下调细胞表面的BST-2，保证病毒的正常释放。Vpu 跨膜区与BST-2跨膜区的相互作用是Vpu对BST-2拮抗作用的关键。在本项目的实施中，我们以分子病毒学为基础，结合分子模拟、化学生物学及生物分析等技术手段，优化Vpu和BST-2跨膜区结合模型，在此基础上进行活性分子设计,并获得活性分子，进而利用所得活性分子进行Vpu下调细胞表面BST-2分子机制研究。该项目的开展不仅将推动宿主固有免疫系统基础研究的深入，而且为应用宿主限制因子BST-2防治HIV-1和其他包膜病毒感染为方向的药物研发奠定基础。