Structural Biology Center for HIV/HOST Interactions in Trafficking and Assembly

我们将建立一个综合性中心，研究涉及病毒贩运和组装的艾滋病毒/宿主相互作用的结构生物学。我们的工作将集中在四个方面：1)病毒RNA和Gag的运输，2)病毒萌发，3)病毒结构，4)早期事件和TRIM5a限制。我们的研究旨在确定REV依赖的核输出的分子基础，揭示促进病毒萌发的宿主/病毒复合体和酶的结构，并以前所未有的细节重建未成熟和成熟的HIV-1病毒粒子。合作互动将扩展我们的研究，包括TRIM5a限制的结构研究，HIV-1 Nef的传染性增强，以及病毒复制早期涉及的一系列宿主因素。我们还将开发和应用新的计算和实验方法来分析宿主/病毒复合体，成像它们如何在细胞中流动，研究它们如何作为分子机器发挥作用，并抑制它们的功能。这项工作将为新的抗病毒策略奠定基础，并将有助于将艾滋病毒发展成为研究人类病毒如何与其细胞宿主相互作用的无与伦比的模型系统。

We will establish a comprehensive Center to study the structural biology of HIV/Host interactions involved in viral trafficking and assembly. Our work will be focused in four areas: 1) Viral RNA and Gag Trafficking, 2) Virus Budding, 3) Virus Structure, and 4) Early Events and TRIM5a Restriction. Our studies are designed to define the molecular basis for Rev-dependent nuclear export, reveal the structures of host/virus complexes and enzymes that facilitate virus budding, and reconstruct the immature and mature HIV-1 virions in unprecedented detail. Collaborative interactions will extend our research to include structural studies of TRIM5a restriction, the infectivity enhancement of HIV-1 Nef, and a series of host factors involved in the early stages of viral replication. We will also develop and apply new computational and experimental methods for analyzing host/virus complexes, imaging how they traffic in the cell, studying how they function as molecular machines, and inhibiting their functions. This work will lay the groundwork for new antiviral strategies and will also help develop HIV into an unparalleled model system for studying how a human virus interacts with its cellular host.