HIV VPX/VPR STRUCTURE/FUNCTION

VPR和VPX是由祖先重组事件产生的，并授予 灵长类慢病毒的多种特性，包括 在静止的细胞中复制。VPR和VPX被包装成病毒粒子 与GAG蛋白相当的量，并介导 预整合复合体进入未分裂细胞的细胞核。这个 目前的建议是继续对新型包装的研究 VPR和VPX的决定因素，对整合前复合体的剖析 运输机制和相互作用的细胞蛋白质的探索 这可能会调解这些和其他活动。具体目标涉及 以下问题： 1.VPR/x包装成病毒粒子的决定因素是什么？如何 它们能用吗？ A.包装用VPX中的序列决定因素是什么？ VPX包装用HIV-2Gag中的序列决定因素是什么？ HIV-2 VPR包装的序列决定因素是什么？ 2.VPR/x在将复杂传输预整合到 原子核？ A.VPR磷酸化在核运输中的作用是什么？ HIV-1 VPR的哪些决定因素调节整合前复合体 交通工具？ Vpx的哪些决定因素调节整合前运输？ 3.VPR/x相互作用细胞蛋白在HIV中的作用 感染？ A.LI与VPX的交互作用是什么？ B.是否还有其他与VPX相互作用的蛋白质，它们是否与VPX相互作用 VPR？

Vpr and Vpx arose by an ancestral recombination event, and confer diverse properties upon primate lentiviruses, including the ability to replicate in quiescent cells. Vpr and Vpx are packaged into virions in amounts comparable to Gag proteins and mediate the transport of preintegration complexes into the nucleus of non-dividing cells. The current proposal is for continuation of studies of the novel packaging determinants of Vpr and Vpx, dissection of the preintegration complex transport mechanisms, and exploration of interactive cellular proteins that may mediate these and other activities. The specific aims address the following question: 1. What are the determinants of Vpr/x Packaging into Virions and how do they work? a. What are the sequence determinants in Vpx for Packaging? b. What are the sequence determinants in HIV-2 Gag for Vpx Packaging? c. What are the sequence determinants for HIV-2 Vpr Packaging? 2. What are the roles of Vpr/x in Preintegration Complex Transport into the Nucleus? a. What is the role of Vpr phosphorylation in nuclear transport? b. What determinants of HIV-1 Vpr regulate preintegration complex transport? c. What determinants of Vpx regulate preintegration transport? 3. What are the roles of Vpr/x Interactive Cellular Proteins in HIV Infection? a. What is the role of li interaction with Vpx? b. Are there other Vpx- interactive proteins, and do they interact with Vpr?