HIV持续感染所引起的艾滋病严重威胁人类健康。宿主与病毒长期共存过程中进化产生多种抗病毒因子，病毒也进化出相应的拮抗或逃逸机制。宿主抗HIV因子的发现、机理分析及病毒拮抗或逃逸机制研究对于深入了解病毒复制机理至关重要，也是开发新的防、治艾滋病策略的基础。前期研究中，我们鉴定了3个新的宿主抗HIV因子，我们命名为iGAT、iPRF、iVIP。在培养细胞中过表达这些因子显著抑制HIV假病毒NL4-3luc的产生；敲低这些因子明显促进假病毒的产生。本项目研究将重点分析这3个因子与HIV相互作用的分子机理。我们将系统分析这些因子在哪一步阻断假病毒的产生，进而详细分析其阻断病毒产生的分子机理。我们将进一步分析这些因子对HIV活病毒复制的影响，据此分析病毒拮抗或逃逸这些因子的作用机制。同时我们还将继续深入研究ZAP、M2BP两个抗HIV-1因子的详细作用机理。本研究组长期研究HIV与宿主相互作用机理，积累了丰富的研究经验，将保障本项目的顺利进行。

Chronic infection by HIV-1 causes AIDS, a highly threatening disease. The host has evolved a variety of mechanisms to inhibit HIV-1 infection, and the virus has also evolved multiple counteracting strategies. Identification and mechanistic characterization of novel host anti-HIV factors are important for further understanding the replication of the virus and thus constitute the basis for the development of new therapeutic strategies. In our previous studies, we identified three novel host anti-HIV factors, iGAT, iPRF and iVIP. Overexpression of each of these factors inhibited the production of VSV-G pseudotyped HIV-1 vector NL4-3luc, and downregulation of each of these factors promoted viral production. In the present study, we aim to understand the molecular mechanisms underlying the interactions between HIV-1 and these host anti-HIV factors. We will first systematically analyze at which step each of these factors inhibits the production of HIV-1vector NL4-3luc. Based on the results, we will further characterize the mechanisms in depth. We will analyze the effect of each factor on the replication of live HIV-1 virus. If the live virus is resistant to any of the factors, we aim to understand the mechanisms for the virus to antagonize the antiviral factor. If the live virus is susceptible to a antiviral factor, we aim to understand how the virus evades the factor in vivo. In addition, we will continue our mechanistic studies on two known anti-HIV factors, ZAP and M2BP.Our group have been working on the interactions between HIV-1 and the host for more than a decade. With the knowledge, expertise and reagents we have collected, we believe we can successfully carry out this project.