Behavior of HIV in Viral Environments (B-HIVE)

HIV 在病毒环境中的行为 (B-HIVE)

• 批准号: 10650864
• 负责人: Stefan G Sarafianos
• 金额: $ 675.93万
• 依托单位: SEATTLE CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-06-22 至 2027-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10650864
• 关键词: Acquired Immunodeficiency Syndrome; Behavior; Binding Sites; Biological; Biophysics; Capsid; Cell Communication; Cell Nucleus; Cells; Characteristics; Chemicals; Collaborations; Communication; Computational Biology; Cytoplasm; Disease; Environment; Evolution; Funding; Genetic Transcription; Genome; Goals; HIV; HIV Integrase; HIV-1; HIV/AIDS; Human Resources; Infection; Infrastructure; Integration Host Factors; Joints; Leadership; Life Cycle Stages; Mentors; Modeling; Molecular; Nuclear; Nuclear Accidents; Nucleic Acids; Nucleosome Core Particle; Pathogenesis; Positioning Attribute; Production; Proteins; Publications; RNA; RNA-Directed DNA Polymerase; Research; Research Personnel; Role; Scientific Advances and Accomplishments; Shapes; Site; Synthesis Chemistry; Testing; Training; United States National Institutes of Health; Universities; Viral; Viral Packaging; Virus; Virus Replication; Washington; experience; gene product; inhibitor; insight; integration site; member; next generation; novel; novel therapeutic intervention; organizational structure; outreach; particle; programs; protein complex; small molecule; small molecule inhibitor; success; trafficking; viral RNA; virology; Acquired Immunodeficiency Syndrome; Behavior; Binding Sites; Biological; Biophysics; Capsid; Cell Communication; Cell Nucleus; Cells; Characteristics; Chemicals; Collaborations; Communication; Computational Biology; Cytoplasm; Disease; Environment; Evolution; Funding; Genetic Transcription; Genome; Goals; HIV; HIV Integrase; HIV-1; HIV/AIDS; Human Resources; Infection; Infrastructure; Integration Host Factors; Joints; Leadership; Life Cycle Stages; Mentors; Modeling; Molecular; Nuclear; Nuclear Accidents; Nucleic Acids; Nucleosome Core Particle; Pathogenesis; Positioning Attribute; Production; Proteins; Publications; RNA; RNA-Directed DNA Polymerase; Research; Research Personnel; Role; Scientific Advances and Accomplishments; Shapes; Site; Synthesis Chemistry; Testing; Training; United States National Institutes of Health; Universities; Viral; Viral Packaging; Virus; Virus Replication; Washington; experience; gene product; inhibitor; insight; integration site; member; next generation; novel; novel therapeutic intervention; organizational structure; outreach; particle; programs; protein complex; small molecule; small molecule inhibitor; success; trafficking; viral RNA; virology

ABSTRACT, OVERVIEW The Behavior of HIV In Viral Environments (B-HIVE) Center has been formed to further the understanding of HIV-1 and HIV-1/cellular host factor macromolecular interactions within distinct cellular environments, which shape the HIV replication cycle. With the limited size of HIV’s RNA genome, it is no surprise that many of the same gene products end up performing different functions in different cellular environments at different times during replication. These various HIV-1-cell host factor interactions promote the cellular pathogenesis, and ultimately disease, characteristic of HIV-1/AIDS. All members have joined the B-HIVE Center with the common goal to collaboratively investigate the dynamic HIV-1 and HIV-1/cellular host factor macromolecular interactions within distinct cellular environments that occur during infection. The B-HIVE Center will capitalize on well- established collaborations between top HIV researchers and scientific accomplishments that provide the rationale to ask new and challenging questions and will be informed by the former HIVE Center (HIV Interaction and Viral Evolution), an organizational structure proven to be effective at not only HIV-1 research, but also by exemplary communication to training, and outreach activities. The B-HIVE team of highly collaborative investigators includes well-established experts in structural, biophysical, chemical, and computational biology, virology, and synthetic chemistry. Only as a Center do the researchers have the necessary combined expertise and critical mass to effectively study the dynamic and mechanistic implications of macromolecular interactions of HIV and cellular host factors within distinct cellular environments. The overall aims of the B-HIVE are organized around three complementary Projects that focus on specific stages of the viral replication cycle: Project 1. Dynamic HIV-1 core interactions with host factors and inhibitors from cytoplasm to nucleus. Aim 1. To discover and characterize novel, dynamic interactions between HIV-1 CA and host cell during virus ingress. Aim 2. To characterize interactions of novel small molecule inhibitors with distinct sites on HIV-1 CA. Project 2. Structural dynamics of HIV-1 nuclear trafficking, integration, and transition to transcription. Aim1. Elucidate dynamic HIV-1 core-host cell interactions crucial for nuclear trafficking, uncoating, and integration. Aim 2. Define the structural and dynamic nuclear events underlying HIV-1 integration site selection. Aim 3. Determine the interplay between integration site and transcriptional latency. Project 3. The dynamics of HIV-1 packaging and assembly. Aim 1. Study the mechanism of HIV-1 RNA genome packaging and the proteins complexed with HIV-1 RNA. Aim 2. Probe the cellular dynamics of the interactions between HIV-1 Gag and identified cellular factors that alter HIV-1 production. Aim 3. Elucidate the dynamics of model Gag assembly and particle formation.

摘要，概述 艾滋病毒在病毒环境中的行为（b-hive）中心已形成，以进一步理解 HIV-1和HIV-1/细胞宿主因子大分子相互作用在不同的细胞环境中 塑造HIV复制周期。由于艾滋病毒的RNA基因组的大小有限，许多人都毫不奇怪 相同的基因产物最终在不同时间在不同的细胞环境中执行不同的功能 在复制过程中。这些各种HIV-1细胞宿主因子相互作用促进了细胞发病机理，并 最终疾病，HIV-1/艾滋病的特征。所有成员都加入了B-hive中心 协作研究动态HIV-1和HIV-1/细胞宿主因子大分子相互作用的目标 在感染过程中发生的不同细胞环境中。 B-hive中心将利用 艾滋病毒顶级研究人员与科学成就之间建立了合作 提出新的和挑战问题的理由，并将由前Hive Center（HIV互动）告知 和病毒进化），一种组织结构不仅在HIV-1研究中也有效 示例与培训和外展活动的沟通。高度合作的B-HY团队 研究人员包括结构，生物物理，化学和计算生物学的公认专家， 病毒学和合成化学。只有作为中心，研究人员才有必要的综合专业知识 和临界质量，以有效研究大分子相互作用的动态和机械意义 艾滋病毒和细胞宿主因子在不同的细胞环境中。 B hive的总体目标是组织的 大约三个完善病毒复制周期特定阶段的完整项目： 项目1。动态HIV-1核心与宿主因子和抑制剂从细胞质到核的抑制剂的相互作用。 目的1。在病毒期间发现并表征HIV-1 CA与宿主细胞之间的新颖的动态相互作用 入口。目标2。表征新型小分子抑制剂与HIV-1 Ca上不同位点的相互作用。 项目2。HIV-1核运输，整合和转录过渡的结构动力学。 AIM1。阐明动态HIV-1核心宿主宿主细胞相互作用对于核运输，脱涂和 一体化。目标2。定义HIV-1整合位点选择的基础结构和动态核事件。 目标3。确定集成位点和转录延迟之间的相互作用。 项目3。HIV-1包装和组装的动力学。 AIM 1。研究HIV-1 RNA基因组包装的机制和与HIV-1 RNA复合的蛋白质。 AIM 2。探测HIV-1 GAG与鉴定的细胞因子之间相互作用的细胞动力学 改变HIV-1的产生。 AIM 3。阐明模型插科打组装和颗粒形成的动力学。