Center for the Structural Biology of Cellular Host Elements in Egress, Trafficking, and Assembly of HIV (CHEETAH Center)

HIV 出口、贩运和组装中细胞宿主元件的结构生物学中心（CHEETAH 中心）

• 批准号: 10221472
• 负责人: WESLEY I. SUNDQUIST
• 金额: $ 478.89万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-08-27 至 2022-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10221472
• 关键词: ATP phosphohydrolase; Anatomy; Animals; Antibodies; Antiviral Therapy; Award; Biological; Biological Assay; Biological Models; Biology; Biophysics; Capsid; Cells; Cellular Structures; Cellular biology; Collaborations; Complex; Computational Science; Cryoelectron Microscopy; Data Science; Development; Dimensions; Electrons; Elements; Enzymes; Face; Family; Filament; Funding; Genes; Genetic; Goals; HIV; HIV Budding; HIV-1; Human; Image; Imaging technology; Immune response; Immunologic Receptors; Immunology; Individual; Innate Immune Response; Integration Host Factors; Laboratories; Learning; Life Cycle Stages; Light; Lysine-Specific tRNA; Maintenance; Mediating; Membrane; Membrane Fusion; Methods; Micro Electron Diffraction; Microscopy; Modeling; Molecular; Molecular Conformation; Molecular Machines; Molecular Virology; Mus; Natural Immunity; Neck; Pathway interactions; Peptides; Primates; Process; Protein Engineering; Proteins; RNA; RNA-Directed DNA Polymerase; Reagent; Replication Initiation; Research Personnel; Resolution; Resources; Reverse Transcription; Spectrum Analysis; Structure; System; T-Lymphocyte; Therapeutic Intervention; Tissues; Toxic effect; Viral; Virion; Virus; Virus Assembly; Virus Latency; Virus Replication; animation; cellular imaging; cellular transduction; design; env Gene Products; env Glycoproteins; experimental study; frontier; humanized mouse; in vitro Model; interdisciplinary approach; macromolecule; mouse model; nonhuman primate; novel strategies; outreach; particle; programs; reactivation from latency; receptor; reconstitution; reconstruction; recruit; screening; simulation; structural biology; targeted treatment; three dimensional structure; tool; tool development; trafficking; transmission process; viral RNA; viral transmission; virology; virus host interaction

ABSTRACT Our Center for the Structural Biology of Cellular Host Elements in Egress, Trafficking, and Assembly of HIV (CHEETAH) studies HIV-Host interactions involved in viral replication, trafficking and transmission. Our studies focus on four key aspects of HIV-1 biology: 1) HIV assembly and host budding restrictions, 2) HIV transmission in whole animals and in vitro models, 3) Intracellular trafficking, transformations and restriction of the viral core, and 4) New directions in viral latency and immune receptors. In each case, we aim to understand: 1) The relevant molecular machines, 2) The mechanisms by which host pathways are recruited and utilized, and 3) The structures of underlying tissues, cellular assemblies, and viral components. Two other overarching themes of the Center are: 1) Studies of dynamic processes, ranging from key molecular transformations in the viral life cycle to studies of virus transmission and dissemination in whole animals, and 2) Developing and applying complementary approaches for studying viral and cellular structures across a range of resolutions, spatial and temporal dimensions, and biological contexts. In parallel, we are developing and applying tools that will advance important frontiers in structural biology and HIV molecular virology, including: 1) New approaches for transforming cryo-EM reconstructions, 2) Correlated light and electron cryotomography (CLEM-ECT) approaches for visualizing viral complexes inside cells, 3) Imaging HIV transmission in humanized mice and primate tissues, and 4) Designing new proteins that can mimic viral assembly, release, and entry. All of these efforts are supported by state-of-the-art Cores for: 1) Producing biological reagents, 2) Performing structural biology, 3) Spectroscopy and imaging, 4) Computation and data science, and 5) Biological models. The efforts of our Center are also extended through: 1) Extensive collaborations with other researchers and P50 Centers, 2) A Collaborative Development Awards program that will fund promising young investigators who will enhance and benefit from interactions with our Center, and 3) Educational programs for Center trainees. Our overall goals are to continue to develop HIV into an unparalleled model system for studying how a human virus interacts with its host, and to lay the groundwork for the development of new antiviral therapies.

抽象的 我们的流出，贩运和艾滋病毒组装中细胞宿主元素结构生物学中心 （Cheetah）研究涉及病毒复制，贩运和传播的HIV主持人相互作用。我们的研究 专注于HIV-1生物学的四个关键方面：1）HIV组装和宿主萌芽限制，2）HIV传播 在整个动物和体外模型中，3）病毒核心的细胞内运输，转化和限制， 4）病毒潜伏期和免疫受体的新方向。在每种情况下，我们的目标是了解：1） 相关分子机，2）募集和利用宿主通路的机制，以及3） 基础组织，细胞组件和病毒成分的结构。另外两个总体主题 中心的是：1）动态过程的研究，范围从病毒寿命的关键分子转化范围 循环到整个动物的病毒传播和传播的研究，以及2）开发和应用 跨空间和一系列分辨率研究病毒和细胞结构的互补方法 时间维度和生物环境。 同时，我们正在开发和应用工具，这些工具将在结构生物学和 HIV分子病毒学，包括：1）转化低温EM重建的新方法，2）相关 光和电子冷冻学（CLEM-ECT）方法可视化细胞内病毒复合物的方法，3） 在人源化小鼠和灵长类组织中成像HIV传播，以及4）设计可以的新蛋白 模仿病毒组装，释放和进入。 所有这些努力得到最先进的核心的支持：1）生产生物试剂，2）执行 结构生物学，3）光谱和成像，4）计算和数据科学，以及5）生物模型。 我们中心的努力也通过：1）与其他研究人员以及 P50中心，2）一个合作发展奖计划，将资助有前途的年轻调查员 谁将从与我们的中心的互动中增强和受益，以及3）中心的教育计划 学员。 我们的总体目标是继续将艾滋病毒发展为无与伦比的模型系统，以研究人类 病毒与其宿主相互作用，并为开发新的抗病毒疗法奠定基础。

项目成果

Deciphering the Structure and Function of Nuclear Pores Using Single-Molecule Fluorescence Approaches.

• DOI: 10.1016/j.jmb.2016.02.023
• 发表时间: 2016-05-22
• 期刊: Journal of molecular biology
• 影响因子: 5.6
• 作者: Musser SM;Grünwald D
• 通讯作者: Grünwald D

Th17 Cells Are Preferentially Infected Very Early after Vaginal Transmission of SIV in Macaques.

• DOI: 10.1016/j.chom.2016.03.005
• 发表时间: 2016-04-13
• 期刊: Cell host & microbe
• 影响因子: 30.3
• 作者: Stieh DJ;Matias E;Xu H;Fought AJ;Blanchard JL;Marx PA;Veazey RS;Hope TJ
• 通讯作者: Hope TJ

Coarse-grained simulation reveals key features of HIV-1 capsid self-assembly.

• DOI: 10.1038/ncomms11568
• 发表时间: 2016-05-13
• 期刊: Nature communications
• 影响因子: 16.6
• 作者: Grime JMA;Dama JF;Ganser-Pornillos BK;Woodward CL;Jensen GJ;Yeager M;Voth GA
• 通讯作者: Voth GA

Correlated cryogenic fluorescence microscopy and electron cryo-tomography shows that exogenous TRIM5α can form hexagonal lattices or autophagy aggregates in vivo.

• DOI: 10.1073/pnas.1920323117
• 发表时间: 2020-11-24
• 期刊: Proceedings of the National Academy of Sciences of the United States of America
• 影响因子: 11.1
• 作者: Carter SD;Mamede JI;Hope TJ;Jensen GJ
• 通讯作者: Jensen GJ

A Sec14-like phosphatidylinositol transfer protein paralog defines a novel class of heme-binding proteins.

Sec14 样磷脂酰肌醇转移蛋白旁系同源物定义了一类新型血红素结合蛋白。

• DOI: 10.7554/elife.57081
• 发表时间: 2020
• 期刊: eLife
• 影响因子: 7.7
• 作者: Khan,Danish;Lee,Dongju;Gulten,Gulcin;Aggarwal,Anup;Wofford,Joshua;Krieger,Inna;Tripathi,Ashutosh;Patrick,JohnW;Eckert,DebraM;Laganowsky,Arthur;Sacchettini,James;Lindahl,Paul;Bankaitis,VytasA
• 通讯作者: Bankaitis,VytasA