Malim M H, Hauber J, Fenrick R, Cullen B R
Howard Hughes Medical Institute, Duke University Medical Center, Durham, North Carolina 27710.
Nature. 1988 Sep 8;335(6186):181-3. doi: 10.1038/335181a0.
The pathogenic human retrovirus human immunodeficiency virus type 1 (HIV-1) encodes two trans-acting nuclear proteins, tat and rev, whose functional expression is essential for viral replication in vitro. The tat protein greatly enhances the expression of both structural and regulatory genes of HIV-1 (linked to the viral long-terminal-repeat promoter element), whereas the rev gene product (previously termed art or trs) has only been shown to be required for the synthesis of structural proteins. Here, we demonstrate that rev also moderates the expression of regulatory genes of HIV-1. It decreases the expression of messenger RNAs that encode the full-length form of the viral tat gene product or the rev protein itself, and induces the synthesis of a previously unreported, truncated tat protein. These actions of rev are mediated by a dramatic shift in the ratio of spliced to unspliced cytoplasmic HIV-1 mRNA. Therefore rev not only activates the synthesis of the viral structural proteins, but also modulates the level and quality of HIV-1 regulatory gene expression.
致病性人类逆转录病毒1型人类免疫缺陷病毒（HIV-1）编码两种反式作用核蛋白，即tat和rev，它们的功能性表达对于病毒在体外的复制至关重要。tat蛋白极大地增强了HIV-1结构基因和调节基因的表达（与病毒长末端重复启动子元件相关），而rev基因产物（以前称为art或trs）仅被证明是结构蛋白合成所必需的。在这里，我们证明rev也调节HIV-1调节基因的表达。它降低了编码病毒tat基因产物全长形式或rev蛋白本身的信使RNA的表达，并诱导合成一种以前未报道的截短型tat蛋白。rev的这些作用是由剪接与未剪接的细胞质HIV-1 mRNA比例的显著变化介导的。因此，rev不仅激活病毒结构蛋白的合成，还调节HIV-1调节基因表达的水平和质量。
