Retroviral Gag Trafficking, Env Incorporation, and Virus Assembly

逆转录病毒堵嘴贩运、Env 合并和病毒组装

• 批准号: 8349150
• 负责人: eric freed
• 金额: $ 53.78万
• 依托单位: DIVISION OF BASIC SCIENCES - NCI
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8349150
• 关键词: ADP-Ribosylation Factors; Address; Binding; Cell membrane; Cells; Data; Destinations; Ear; Equine Infectious Anemia Virus; Feline Immunodeficiency Virus; Gagging; Glycoproteins; Goals; Golgi Apparatus; HIV Drug Resistance Program; HIV-1; Life; Lipids; Membrane; Movement; Phosphatidylinositols; Play; Proteins; Reporting; Role; Site; Site Visit; Subfamily lentivirinae; Synapses; Viral; Virion; Virus; Virus Assembly; Work; cell type; cellular imaging; interest; macrophage; trafficking; virological synapse

In most cell types, HIV-1 assembly occurs predominantly on the plasma membrane; however, the itinerary that the Gag precursor follows to reach its destination in the cell and the role that cellular factors play in Gag trafficking remain ill defined. We discovered that a lipid, the phosphoinositide PI(4,5)P2, serves an important function in directing Pr55Gag to the plasma membrane. We are actively engaged in studies that seek to elucidate further the cellular machinery involved in HIV-1 Gag trafficking. This effort builds upon our recent finding that the ADP ribosylation factors (Arfs) and the Golgi-localized, gamma-ear-containing, Arf-binding (GGA) proteins modulate Gag-membrane binding and virus release. Additional Gag partners have recently been identified. These studies, which focus primarily on HIV-1, are also being extended to the nonprimate lentiviruses equine infectious anemia virus (EIAV) and feline immunodeficiency virus (FIV). We recently reported live-cell imaging data demonstrating the movement of HIV-1 Gag to the cell-cell contact site (virological synapse) in infected macrophages; we are currently working to define both viral and cellular determinants that direct Gag to the macrophage synapse. We are also pursuing a long-term interest in the mechanism by which the viral envelope (Env) glycoproteins are incorporated into virus particles. The role of host cell factors in Env incorporation, which remains unresolved and controversial, is being addressed in ongoing studies. [Corresponds to Freed Project 1 in the April 2007 site visit report of the HIV Drug Resistance Program]

在大多数细胞类型中，HIV-1组装主要发生在质膜上。但是，插科打术前体遵循的行程是到达其在细胞中的目的地，并且细胞因子在堵嘴贩运中的作用仍然不明显。我们发现脂质，磷酸肌醇PI（4,5）P2在将PR55GAG引导到质膜方面起着重要功能。我们正在积极从事研究，以进一步阐明与HIV-1堵嘴贩运有关的细胞机制。这项工作是基于我们最近的发现，即ADP核糖基化因子（ARF）和高尔基体定位，含γ-耳的含量，ARF结合（GGA）蛋白会调节GAG-膜结合和病毒的释放。最近已经确定了其他插科打伙伴。这些主要集中于HIV-1的研究也已扩展到非雄性厌食症，马传染病病毒（EIAV）和猫免疫缺陷病毒（FIV）。我们最近报道了活细胞成像数据，证明了HIV-1 GAG向感染巨噬细胞中的细胞 - 细胞接触位点（病毒学突触）运动。我们目前正在努力定义直接堵嘴的病毒和细胞决定因素。我们还对病毒包膜（ENV）糖蛋白纳入病毒颗粒的机制进行了长期的兴趣。在正在进行的研究中正在解决宿主细胞因素在环境中的作用，尚未解决和争议。 [对应于2007年4月的艾滋病毒抗药性计划的现场访问报告中的释放项目1]