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

描述(由申请人提供)： 我们的HIV出口、贩运和组装中的细胞宿主元素结构生物学中心(猎豹)研究艾滋病毒-宿主相互作用的结构生物学，涉及病毒的贩运和组装(广义定义)。我们的生物学研究将集中在HIV-1生命周期的五个关键方面的结构生物学、生物化学、细胞生物学和分子病毒学：1)反转录和整合前复合体的转化和运输，2)TRIM5a限制，3)REV依赖的死盒解旋酶转化，4)病毒粒子的组装和萌发，以及5)病毒粒子的结构、能量和成熟。在每一种情况下，我们的目标是了解：1)驱动这些事件的分子机器，2)招募和利用宿主途径的机制，以及3)潜在的病毒和细胞结构。同时，我们将在四个不同的领域进行技术开发，这些领域将促进我们的生物学研究，并成为艾滋病毒研究的重要前沿：1)天然REV复合体的单分子分析，2)病毒衣壳结构和组装的多尺度计算机模拟，3)病毒成像的进展，以及4)组织中艾滋病毒成像方法的开发和应用。我们中心的努力还将通过：1)与其他PSO中心和同事的广泛合作，并获得生物医学界的科学资源；2)合作发展计划，将资助有前途的合作者，他们将加强与我们中心的互动并从中受益；以及3)年轻科学家的培训计划。我们的总体目标是为开发新的抗病毒战略奠定基础，并继续将艾滋病毒发展成为研究人类病毒如何与宿主相互作用的无与伦比的模型系统。

DESCRIPTION (provided by applicant): Our Center for the Structural Biology of Cellular Host Elements in Egress, Trafficking, and Assembly of HIV (CHEETAH) studies the structural biology of HIV-Host interactions involved in viral trafficking and assembly (as broadly defined). Our biological studies will focus on the structural biology, biochemistry, cell biology and molecular virology of five key aspects of the HIV-1 life cycle: 1) Reverse transcription and preintegration complex transformations and trafficking, 2) TRIM5a restriction, 3) Rev-dependent DEAD-box helicase transformations, 4) Virion assembly and budding, and 5) Virion structure, energetics and maturation. In each case, we aim to understand: 1) The molecular machines that drive these events, 2) The mechanisms by which host pathways are recruited and utilized, and 3) The underlying viral and cellular structures. In parallel, we will pursue technological developments in four different areas that will facilitate our biological studies and are important frontiers in HIV research: 1) Single-molecule analyses of native Rev complexes, 2) Multiscale computer simulations of viral capsid structure and assembly, 3) Advances in virus imaging, and 4) Development and application of methodology for imaging HIV in tissues. The efforts of our Center will also be extended through: 1) Extensive collaborations with other PSO Centers and colleagues, and access to scientific resources within the biomedical community, 2) A Collaborative Development Program that will fund promising collaborators who will enhance and benefit from interactions with our Center, and 3) Training programs for younger scientists. Our overall goals are to lay the groundwork for development of new antiviral strategies and to continue to develop HIV into an unparalleled model system for studying how a human virus interacts with its host.