Behavior of HIV in Viral Environments (B-HIVE)

摘要，概述 艾滋病毒在病毒环境中的行为(B-HIVE)中心已经成立，以进一步了解 HIV-1和HIV-1/细胞宿主因子在不同的细胞环境中的大分子相互作用，这 塑造艾滋病毒复制周期。由于艾滋病毒RNA基因组的有限大小，难怪许多 相同的基因产物最终在不同的细胞环境中在不同的时间发挥不同的功能 在复制期间。这些不同的HIV-1与细胞宿主因子的相互作用促进了细胞的发病机制，并且 最终的疾病，艾滋病毒-1/艾滋病的特征。所有成员都加入了B-HIVE中心， 目的研究HIV-1和HIV-1/细胞宿主因子大分子间的动态相互作用 在感染期间发生的不同的细胞环境中。B-HIVE中心将充分利用- 顶尖艾滋病毒研究人员和科学成就之间建立的合作提供了 提出新的和具有挑战性的问题的理由，并将由前蜂巢中心(艾滋病毒互动)提供信息 和病毒进化)，这种组织结构被证明不仅在艾滋病毒-1研究方面有效，而且通过 模范的沟通、培训和外联活动。高度协作的B-HIVE团队 研究人员包括结构、生物物理、化学和计算生物学方面的知名专家， 病毒学和合成化学。只有作为一个中心，研究人员才能拥有必要的综合专业知识 和临界质量来有效地研究大分子相互作用的动力学和力学含义 在不同的细胞环境中对艾滋病毒和细胞宿主因素的影响。B-HIVE的总体目标是有组织的 大约有三个补充项目侧重于病毒复制周期的特定阶段： 项目1.HIV-1核心与宿主因子和抑制物从细胞质到细胞核的动态相互作用。 目的1.发现和表征HIV-1 CA与宿主细胞在病毒感染过程中的动态相互作用 入口。目的2.研究新型小分子抑制剂与HIV-1CA上不同位点的相互作用。 项目2.艾滋病毒-1核贩运、整合和向转录过渡的结构动态。 目的：1.阐明HIV-1核心-宿主细胞的动态相互作用对核运输、脱壳和 整合。目标2.确定作为HIV-1整合地点选择基础的结构性和动态核事件。 目的3.确定整合位点和转录潜伏期之间的相互作用。 项目3.艾滋病毒-1包装和组装的动态。 目的1.研究HIV-1RNA的基因组包装机制及其与HIV-1RNA的结合蛋白。 目的2.探索HIV-1 Gag与已鉴定的细胞因子相互作用的细胞动力学 改变HIV-1的生产。目的3.阐明模型GAG组装和颗粒形成的动力学。

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.