免疫缺陷病毒（HIV）感染引起的旁观T细胞凋亡是造成T细胞数量大量减少和艾滋病发病的原因，死亡配体蛋白FASL在这一过程中起主导作用。我们前期的研究发现凋亡相关蛋白ALG-2可以抑制HIV的产生，而且ALG-2与FASL有直接的相互作用。初步的实验结果证明ALG-2的敲除可以显著抑制PMA/Ionomycin激活和病毒感染诱导的T细胞凋亡。本项目抓住ALG-2和FASL有直接相互作用这一新发现，从ALG-2/FASL复合物结构和功能的关系入手，探索HIV感染引起的T细胞凋亡的机理。ALG-2对FASL的翻译后调控机制研究，将是对FASL控制的T细胞凋亡的一个新的探索方向。我们对ALG-2和FASL相互作用的研究，将会从结构和功能两个方面提供二者相互作用的细节，这些研究结果将会对艾滋病的治疗提供新的思路。

The infection of Human Immunodeficiency Virus (HIV) leads to large amount of T cell depletion in vivo through activation induced cell death, which is associated tightly with the onset of acquired immunodeficiency syndrome (AIDS). Death receptor associated proteins such as FASL-FAS play critical roles in this phenomenon. In our previous work, we found that apoptosis-linked gene 2 (ALG-2) can inhibit HIV production through regulating the expression and localization of HIV Gag. We also found that ALG-2 can interact with FASL directly via N-terminal cytosolic region of FASL in a Ca2+ -dependent manner. The absence of ALG-2 in Jurkat T cells leads to a significant inhibition on cell death following PMA/Ionomycin activation or HIV infection. Beginning from the identification of ALG-2/FASL interaction, in this proposal, we try to determine the crystal structure of ALG-2/FASL complex, and investigate the regulation of ALG-2 on FASL and their influence on T cell apoptosis. Our study on ALG-2 and FASL will provide the details of their interaction and regulation at biochemical and cellular levels, which will extend our understanding on T cell apoptosis induced by HIV infection and contribute to our efforts on AIDS intervention.