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.

摘要 我们的中心的结构生物学的细胞宿主元素在出口，贩运，和大会的艾滋病毒 （CHEETAH）研究涉及病毒复制、贩运和传播的HIV-宿主相互作用。我们的研究 重点关注HIV-1生物学的四个关键方面：1）HIV组装和宿主出芽限制，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， 病毒潜伏期和免疫受体的新方向。在每一种情况下，我们的目标是了解：1） 相关的分子机器，2）宿主途径被招募和利用的机制，以及3） 底层组织的结构、细胞集合体和病毒成分。其他两个重要主题 该中心的主要工作是：1）研究动态过程，从病毒生命中的关键分子转化， 病毒在整个动物体内传播和扩散研究的循环; 2）开发和应用 研究病毒和细胞结构的互补方法，包括一系列分辨率，空间和 时间维度和生物背景。 与此同时，我们正在开发和应用将推进结构生物学重要前沿的工具， HIV分子病毒学，包括：1）转化冷冻EM重建的新方法，2）相关 用于可视化细胞内病毒复合物的光和电子冷冻断层扫描（CLEM-ECT）方法，3） 在人源化小鼠和灵长类动物组织中成像HIV传播，以及4）设计新的蛋白质， 模拟病毒的组装、释放和进入。 所有这些努力都得到了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）光谱学和成像，4）计算和数据科学，以及5）生物模型。 我们中心的努力还通过以下方式扩展：1）与其他研究人员的广泛合作， P50中心，2）合作发展奖计划，将资助有前途的年轻研究人员 他们将加强与我们中心的互动并从中受益，以及3）中心的教育计划 实习生 我们的总体目标是继续将艾滋病毒发展成为一个无与伦比的模型系统，用于研究人类如何感染艾滋病毒。 病毒与宿主相互作用，并为开发新的抗病毒疗法奠定基础。

项目成果

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

Changes in HIV-1 Capsid Stability Induced by Common Cytotoxic-T-Lymphocyte-Driven Viral Sequence Mutations.

常见细胞毒性 T 淋巴细胞驱动的病毒序列突变引起的 HIV-1 衣壳稳定性变化。

• DOI: 10.1128/jvi.00867-16
• 发表时间: 2016
• 期刊: Journal of virology
• 影响因子: 5.4
• 作者: Schommers,P;Martrus,G;Matschl,U;Sirignano,M;Lütgehetmann,M;Richert,L;Hope,TJ;Fätkenheuer,G;Altfeld,M
• 通讯作者: Altfeld,M

Same structure, different mechanisms?

相同的结构，不同的机制？

• DOI: 10.7554/elife.56501
• 发表时间: 2020
• 期刊: eLife
• 影响因子: 7.7
• 作者: Tsai,FrancisTF;Hill,ChristopherP
• 通讯作者: Hill,ChristopherP

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