LENTIVIRUS-HOST INTERACTIONS DURING ASSEMBLY AND RELEASE

描述：本提案的总体目标是提高我们对 控制人类和猫科动物的组装和退出的分子机制 免疫缺陷病毒（分别为HIV-1和FIV）。穿过内部 逆转录病毒的结构蛋白，即所谓的Gag蛋白， 在不存在其他病毒组分的情况下， 病毒包膜糖蛋白（Env）参与控制病毒在 许多病毒从受感染的细胞中释放出来。他们在病毒生命中的地位 因此，循环是关键的，不仅因为它们控制病毒的附着和进入 还因为它们精确地控制了新组装的粒子的出口 在病毒复制周期的晚期阶段从细胞中分离出来。空间 逆转录病毒的限制性定向释放可能特别重要 当受感染的细胞接触潜在的靶细胞时，例如当免疫缺陷 病毒穿过上皮屏障或在它们从外周迁移期间 淋巴器官和中枢神经系统。病毒的调控 因此，病毒的扩散可能会对病毒的传播过程产生重大影响。 传播和发病机制。因此，它也是一个潜在的目标， 治疗干预 我们提出了慢病毒（HIV-1; FIV）晚期事件的分子解剖 使用细胞生物学、生物化学和病毒学方法研究复制周期。 我们的重点是Env在病毒组装和释放过程中的作用， 重点研究Env与宿主细胞蛋白的相互作用， 病毒性加格该提案的具体目标是：1）进一步界定 慢病毒Env（HIV-1; FIV）中的信号， 与细胞运输机器的蛋白质， Env的后高尔基体路由的特征; 2）检验假设 Env转运到特定的亚细胞位点，如在特定的 目标1，负责定向病毒释放，并测试是否错误启动 颗粒脱落损害病毒繁殖。彻底评估 控制病毒释放不对称性的病毒-宿主相互作用将 还为进一步研究提供必要的基础， 鉴定与病毒传播有关的另外的Env晚期功能， 致病性

DESCRIPTION: The overall goal of this proposal is to improve our understanding of the molecular mechanisms which control assembly and exit of human and feline immunodeficiency viruses (HIV-1 and FIV, respectively). Though the internal structural proteins of retroviruses, the so-called Gag proteins, can form membrane-enveloped particles in the absence of other viral components, the viral envelope glycoproteins (Env) are implicated in controlling where and how much virus is released from infected cells. Their position in the viral life cycle is thus pivotal not only because they control virus attachment and entry but also because they regulate where exactly newly assembled particles exit from cells during the late phase of the viral replication cycle. Spatially restricted, directional release of retrovirus may be particularly important when infected cells contact potential target cells, e.g. when immunodeficiency viruses cross epithelial barriers or during their migration from the periphery to lymphoid organs and the central nervous system. The regulation of virus egress is thus likely to influence substantially the course of virus dissemination and pathogenesis. As such it also presents a potential target for therapeutic intervention. We propose a molecular dissection of late events of the lentiviral (HIV-1; FIV) replication cycle using cell-biological, biochemical and virological methods. Our focus is on the role of Env during viral assembly and release and we will put emphasis on studying the interactions of Env with host-cell proteins and with viral Gag. The specific aims ofthis proposal are 1) to further define signals in lentiviral Env (HIV-1; FIV) that are necessary for its association with proteins of the cellular trafficking machinery and thus for the characteristics of the post-Golgi routing of Env; 2) to test the hypothesis that the transport of Env to specific subcellular sites, as defined in Specific Aim 1, is responsible for directional virus release and to test if mistargeting of particle shedding impairs virus propagation. A thorough assessment of virus-host interactions, which control the asymmetry of virus release, will also provide the necessary groundwork for further studies aiming at the identification of additional Env late functions implicated in virus spread and pathogenicity.