HIV-1 REV PROTEIN--BIOCHEMICAL MECHANISMS

描述：HIV-1 Rev蛋白是病毒复制和ACTS所必需的 通过促进未完全剪接的病毒的这种细胞质积累 编码结构蛋白的核糖核酸。REV是一种序列特异的RNA 与病毒RNA元件相互作用的结合蛋白，称为RRE。 此应用程序的两个长期目标是：1)了解如何 REV促进病毒的信使核糖核酸运输和2)发展小分子和 以蛋白质为基础的REV抑制剂。在上一次筹资期间，a 人类rev辅因子(HRIP)的克隆取得了重大进展 这是本应用程序的主要关注点。调查员提议 更详细地研究REV和hRIP如何合作以促进 HIV-1RNA。细胞内m RNA核输出过程较差。 理解，这将是应用程序的主要部分。第二 主要目标是开发REV抑制剂。这个实验室有 证明了某些小分子，如特定的氨基糖苷类 抗生素，它与RRE相互作用，抑制REV结合和REV 功能。对这些小分子RNA相互作用的进一步研究将是 在此应用程序中计算。最后，调查员最近 发现了选择人造多肽的方法，以特定地 与单元格内的REV交互，并可能阻止REV功能。这些研究 将扩展和开发更强大和具体的版本 提出了抑制剂的概念。

DESCRIPTION: HIV-1 Rev protein is required for viral replication and acts by facilitating this cytoplasmic accumulation of incompletely-spliced viral mRNA that encodes structural proteins. Rev is a sequence-specific RNA binding protein which interacts with the viral RNA element designated RRE. The two long-term objectives of this application are to: 1) Understand how Rev facilitates viral mRNA transport and 2) to develop small molecules and protein-based Rev inhibitors. Over the previous period of funding, a significant advance has been the cloning of a human Rev cofactor (hRIP) which is a major focus of this application. The investigator proposes to study in greater detail how Rev and hRIP collaborate to facilitate export of HIV-1 RNAs. The process of cellular mRNA nuclear export is poorly understood and this will be a major portion of the application. The second major objective is to develop Rev inhibitors. This laboratory has demonstrated certain small molecules, such as specific aminoglycoside antibiotics, which interact with the RRE to inhibit Rev binding and Rev function. Further studies on these small molecular RNA interactions will be evaluated in this application. Finally, the investigator has recently discovered methodologies to select artificial peptides to specifically interact with Rev within cells and may block Rev function. These studies will be extended and the development of more potent and specific Rev inhibitors is proposed.