Gatignol A, Duarte M, Daviet L, Chang Y N, Jeang K T
Unité 332 INSERM, Institut Cochin de Génétique Moléculaire, Paris, France.
Gene Expr. 1996;5(4-5):217-28.
The regulation of HIV expression is controlled by the activity of the Long Terminal Repeat (LTR). Trans-activation by the virally encoded Tat protein is one of the main mechanisms of LTR activation. Tat binds to its target, TAR RNA, and cellular proteins that bind the LTR, Tat, or TAR RNA are important components of the trans-activation process. We will review the factors that have been characterized for a possible involvement in this mechanism. Whereas LTR binding proteins consist of Sp1 and TBP, a large number of factors that bind TAR RNA have been isolated. We have previously cloned two of them by RNA probe recognition: TRBP and La. We have shown that the in vitro and in vivo binding of TRBP to TAR RNA correlates with a constant expression of the protein during HIV-1 infection. Several proteins that interact with Tat have mainly positive, but some negative, effects on trans-activation. Genetic studies have defined that human chromosome 12 encodes a protein that will allow trans-activation in rodent cells. The binding and the functional data about these proteins suggest sequential steps for the Tat trans-activation mechanism. Each of these intracellular molecular events could be the target for molecular intervention against the virus.
HIV表达的调控由长末端重复序列（LTR）的活性控制。病毒编码的Tat蛋白的反式激活是LTR激活的主要机制之一。Tat与其靶标TAR RNA结合，而结合LTR、Tat或TAR RNA的细胞蛋白是反式激活过程的重要组成部分。我们将综述已被鉴定可能参与该机制的因素。LTR结合蛋白包括Sp1和TBP，大量结合TAR RNA的因子已被分离出来。我们之前通过RNA探针识别克隆了其中两个：TRBP和La。我们已经表明，TRBP与TAR RNA的体外和体内结合与HIV-1感染期间该蛋白的恒定表达相关。几种与Tat相互作用的蛋白对反式激活主要有正向作用，但也有一些负向作用。遗传学研究表明，人类12号染色体编码一种蛋白，该蛋白能在啮齿动物细胞中实现反式激活。关于这些蛋白的结合和功能数据提示了Tat反式激活机制的连续步骤。这些细胞内分子事件中的每一个都可能成为针对该病毒进行分子干预的靶点。
