Project 1: Structure and dynamics of Gag maturation intermediates and mechanisms of viral genome enclosure

P1。摘要 病毒成熟是HIV-1复制的关键，通过一系列精心安排的Gag和Gag-Pol裂解发生 这导致形成包裹病毒基因组核糖核蛋白复合体的锥形病毒衣壳。HIV-1 成熟是抗病毒药物开发的一个有吸引力的目标，小分子的研究证明了这一点。 抑制剂倍维力马特。在这个项目中，我们将使用结构、生化和病毒学方法来产生新的 对未成熟的Gag晶格的结构和动力学以及成熟抑制剂的影响的见解。我们还将 确定整合酶-RNA相互作用在病毒衣壳内定位RNP的机制。最后，我们会 剖析未裂解的基质衣壳干扰HIV-1成熟的机制。这些研究将揭示新的 HIV-1成熟及其抑制的基本方面。

P1. Abstract Virus maturation is critical for HIV-1 replication and occurs through an orchestrated series of Gag and Gag-Pol cleavages that result in formation of the conical viral capsid enclosing the viral genomic ribonucleoprotein complex. HIV-1 maturation represents an attractive target for antiviral drug development as evidenced by studies of the small molecule inhibitor bevirimat. In this project, we will employ structural, biochemical, and virological methods to generate new insights into the structure and dynamics of the immature Gag lattice and the effects of maturation inhibitors. We will also define the mechanism by which Integrase-RNA interactions localize the RNP within the viral capsid. Finally, we will dissect the mechanism by which uncleaved matrix-capsid interferes with HIV-1 maturation. These studies will reveal new fundamental aspects of HIV-1 maturation and its inhibition.