THE TYPE-I HUMAN T-CELL LEUKEMIA-VIRUS (HTLV-I) REX TRANSACTIVATOR BINDS DIRECTLY TO THE HTLV-I REX AND THE TYPE-1 HUMAN-IMMUNODEFICIENCY-VIRUS REV RNA RESPONSE ELEMENTS
THE TYPE-I HUMAN T-CELL LEUKEMIA-VIRUS (HTLV-I) REX TRANSACTIVATOR BINDS DIRECTLY TO THE HTLV-I REX AND THE TYPE-1 HUMAN-IMMUNODEFICIENCY-VIRUS REV RNA RESPONSE ELEMENTS
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DOI：
10.1073/pnas.88.13.5704
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发表时间：
1991-07-01
影响因子：
11.1
通讯作者：
GREENE, WC
中科院分区：
文献类型：
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作者：
BOGERD, HP;HUCKABY, GL;GREENE, WC
I型人T细胞白血病病毒（HTLV-1）的雷克斯蛋白对于这种致病性逆转录病毒的复制是必需的，并且令人惊讶的是，还可以替代I型人免疫缺陷病毒（HIV-1）的结构上不同的Rev蛋白的功能。雷克斯作用需要位于3'逆转录病毒长末端重复序列中的称为雷克斯RNA应答元件（RexRE）的255个核苷酸的病毒RNA茎环结构。雷克斯功能导致不完全剪接的病毒mRNA家族的诱导细胞质表达，所述病毒mRNA家族独特地编码HTLV-1结构和酶蛋白（Gag、Pol和Env）。我们的研究现在证明，雷克斯的行为直接结合到RexRE的序列特异性的方式。雷克斯的这些作用需要RexRE的10个核苷酸亚区的存在，该亚区对于雷克斯的体内功能是必需的。雷克斯的显性负突变体也以高亲和力结合RexRE，而隐性负雷克斯突变体在其富含丝氨酸的带正电荷的结构域内改变，不能与RexRE结合。类似地，野生型和显性阴性雷克斯蛋白都特异性结合结构上不同的HIV-1 Rev反应元件，这一发现可能是这些HTLV-1蛋白在异源HIV-1系统中各自的刺激和抑制作用的基础。然而，与它们缺乏氨基酸同源性一致，HIV-1 Rev反应元件内的雷克斯和Rev的结合位点是不同的。
The Rex protein of the type I human T-cell leukemia virus (HTLV-I) is essential for the replication of this pathogenic retrovirus and, surprisingly, can also replace the function of the structurally distinct Rev protein of the type 1 human immunodeficiency virus (HIV-1). Rex action requires a 255-nucleotide viral RNA stem-loop structure termed the Rex RNA response element (RexRE) located in the 3' retroviral long terminal repeat. Rex function leads to the induced cytoplasmic expression of the incompletely spliced family of viral mRNAs that uniquely encode the HTLV-I structural and enzymatic proteins (Gag, Pol, and Env). Our studies now demonstrate that Rex acts by binding directly to the RexRE in a sequence-specific manner. These effects of Rex require the presence of a 10-nucleotide subregion of the RexRE that is essential for Rex function in vivo. Dominant-negative mutants of Rex also bind to the RexRE with high affinity, while a recessive-negative Rex mutant altered within its arginine-rich, positively charged domain fails to engage the RexRE. Analogously, both the wild-type and dominant-negative Rex proteins specifically bind to the structurally distinct HIV-1 Rev response element, a finding that likely underlies the respective stimulatory and inhibitory effects of these HTLV-I proteins in the heterologous HIV-1 system. However, consistent with their lack of amino acid homology, the binding sites for Rex and Rev within the HIV-1 Rev response element are distinct.