DR DONG, SALARY SUPPORT ONLY

该子项目是利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得主要资金， 因此可以在其他CRISP条目中表示。列出的机构是 中心，不一定是研究者的机构。 HIV-1 Gag蛋白指导高度协调的颗粒组装和出芽过程。在组装过程中，未切割的Gag多蛋白与病毒RNA和包膜糖蛋白复合物（Env）相互作用以协调感染性病毒体的产生。细胞运输机制被HIV-1 Gag招募，并参与颗粒组装和出芽的重要步骤。我们确定了一种新的相互作用之间的Gag和衔接蛋白复合物AP-3。这种相互作用引导Gag运输到多泡体（MVB）。Gag-AP-3相互作用的破坏阻止Gag到达MVB并抑制颗粒形成。 我们通过筛选人cDNA文库，鉴定了几个GAG结合蛋白。最近，我们正在研究它们在HIV组装中的作用，使用各种方法，如慢病毒介导的基因转移，RNAi介导的基因敲除和定点诱变。这些研究不仅在理解HIV组装过程中细胞因子和病毒蛋白之间的关联方面具有更广泛的生物学意义，而且还为我们设计对抗病毒的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.