IMMUNODEFICIENCY VIRUS REV TRANS-ACTIVATOR MODULATES THE EXPRESSION OF THE VIRAL REGULATORY GENES
IMMUNODEFICIENCY VIRUS REV TRANS-ACTIVATOR MODULATES THE EXPRESSION OF THE VIRAL REGULATORY GENES
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DOI：
10.1038/335181a0
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发表时间：
1988-09-08
期刊：
影响因子：
64.8
通讯作者：
CULLEN, BR
中科院分区：
文献类型：
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作者：
MALIM, MH;HAUBER, J;CULLEN, BR
致病性人类逆转录病毒人类免疫缺陷病毒1型（HIV-1）编码两种反式作用核蛋白tatandrev，其功能表达对病毒体外复制至关重要1 -6。Thetat蛋白极大地增强了HIV-1的结构和调节基因（与病毒长末端重复启动子元件连接）的表达6-13，而Thetat基因产物（以前称为artortrs 14）仅被证明是合成结构蛋白所需的15，16。在这里，我们证明，rev也调节HIV-1的调控基因的表达。它降低了编码全长形式的viraltat基因产物或其蛋白本身的信使RNA的表达，并诱导了以前未报道的截短的dat蛋白的合成。rev的这些作用是由剪接与未剪接的细胞质HIV-1 mRNA的比例的急剧变化介导的。因此，不仅激活病毒结构蛋白的合成，而且调节HIV-1调节基因表达的水平和质量。
The pathogenic human retrovirus human immunodeficiency virus type 1 (HIV-1) encodes twotrans-acting nuclear proteins,tatandrev, whose functional expression is essential for viral replicationin vitro1–6. Thetatprotein greatly enhances the expression of both structural and regulatory genes of HIV-1 (linked to the viral long-terminal-repeat promoter element)6–13, whereas therevgene product (previously termedartortrs14) has only been shown to be required for the synthesis of structural proteins15,16. Here, we demonstrate thatrevalso moderates the expression of regulatory genes of HIV-1. It decreases the expression of messenger RNAs that encode the full-length form of the viraltatgene product or therevprotein itself, and induces the synthesis of a previously unreported, truncatedtatprotein. These actions ofrevare mediated by a dramatic shift in the ratio of spliced to unspliced cytoplasmic HIV-1 mRNA. Thereforerevnot only activates the synthesis of the viral structural proteins, but also modulates the level and quality of HIV-1 regulatory gene expression.