DR DONG, SALARY SUPPORT ONLY

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 HIV-1 Gag蛋白指导着高度协调的颗粒组装和萌芽过程。在组装过程中，未切割的Gag多聚蛋白与病毒RNA和包膜糖蛋白复合体(Env)相互作用，以协调感染性病毒粒子的产生。细胞运输机制是由HIV-1 GAG招募的，参与颗粒组装和萌芽的关键步骤。我们发现了GAG与接头蛋白复合体AP-3之间的一种新的相互作用。这种相互作用将Gag的贩运引导到多囊泡小体(MVB)。GAG-AP-3相互作用的中断阻止了GAG到达MVBS，并抑制了颗粒的形成。 通过筛选人cDNA库，我们已经鉴定了几种与Gag结合的蛋白。最近，我们正在通过慢病毒介导的基因转移、RNAi介导的基因敲除和定点突变等多种方法来研究它们在HIV组装中的作用。这些研究不仅对了解HIV组装过程中细胞因子和病毒蛋白之间的关系具有更广泛的生物学意义，而且为我们设计抗病毒药物提供了新的信息。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The HIV-1 Gag protein directs the highly orchestrated process of particle assembly and budding. During assembly, the uncleaved Gag polyprotein interacts with the viral RNA and the envelope glycoprotein complex (Env) to coordinate the production of infectious virions. The cellular trafficking machinery is recruited by HIV-1 Gag and participates in essential steps of particle assembly and budding. We identified a novel interaction between Gag and adaptor protein complex AP-3. This interaction directs Gag trafficking to multivesicular bodies (MVB). Disruption of Gag-AP-3 interaction prevents Gag from reaching to MVBs and inhibits particle formation. We have identified several Gag-binding proteins by screening human cDNA library. Recently, we are investigating their roles in HIV assembly using variety of approaches such as lentiviral mediated gene transfer, RNAi-mediated gene knockdown and site-directed mutagenesis. These studies not only have broader biological implications in understanding the association between cellular factors and viral proteins during HIV assembly, but also provide us new information to design drugs to combat the virus.