The glucocorticoid receptor type Ⅱ complex is a target of the HIV-1 vpr gene product

YOSEF REFAELI; DAVID N. LEVY; DAVID B. WEINER

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The glucocorticoid receptor type Ⅱ complex is a target of the HIV-1 vpr gene product

机译：糖皮质激素受体Ⅱ型复合物是HIV-1 vpr基因产物的靶标

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The vpr gene of human immunodeficiency virus type 1 (HIV-1) encodes a 15-kDa virion-associated protein that functions as a regulator of cellular processes linked to the HIV life cycle. We report the interaction of a 41-kDa cytosolic viral protein R interacting protein 1 (Rip-1) with Vpr in vitro. Rip-1 displays a wide tissue distribution, including relevant targets of HIV infection. Vpr protein induced nuclear translocation of Rip-1, as did glucocorticoid receptor (GR)-Ⅱ-stimulating steroids. Importantly, Vpr and Rip-1 coimmunoprecipitated with the human GR as part of an activated receptor complex. Vpr complementation of a vpr mutant virus was also mimicked by GR-Ⅱ-stimulating steroids. Vpr and GR-Ⅱ actions were inhibited by mifepristone, a GR-Ⅱ pathway inhibitor. Together these data directly link the activity of the vpr gene product to the glucocorticoid steroid pathway and provide a biochemical mechanism for the cellular and viral activity of Vpr, as well as suggest that a unique class of antivirals, which includes mifepristone (RU486), may influence HIV-1 replication.

机译：人类1型免疫缺陷病毒（HIV-1）的vpr基因编码一个15 kDa的病毒体相关蛋白，可作为与HIV生命周期相关的细胞过程的调节剂。我们报告了41 kDa胞质病毒蛋白R相互作用蛋白1（Rip-1）与Vpr的相互作用。 Rip-1显示出广泛的组织分布，包括HIV感染的相关目标。 Vpr蛋白诱导Rip-1的核易位，糖皮质激素受体（GR）-Ⅱ刺激类固醇也是如此。重要的是，Vpr和Rip-1与人类GR共免疫沉淀，是活化受体复合物的一部分。 vpr突变病毒的vpr互补也被GR-Ⅱ刺激的类固醇模拟。米非司酮是一种GR-Ⅱ途径的抑制剂，可抑制Vpr和GR-Ⅱ的作用。这些数据加在一起，直接将vpr基因产物的活性与糖皮质激素类固醇途径联系起来，并为Vpr的细胞和病毒活性提供了生化机制，并暗示一类独特的抗病毒药，包括米非司酮（RU486），可能影响HIV-1复制。

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《Proceedings of the National Academy of Sciences of the United States of America》 |1995年第8期|p.3621-3625|共5页
作者
YOSEF REFAELI; DAVID N. LEVY; DAVID B. WEINER;
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收录信息美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
原文格式 PDF
正文语种 eng
中图分类自然科学总论;
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1. Antiviral effects of mifepristone on human immunodeficiency virus type-1 (HIV-1): targeting Vpr and its cellular partner, the glucocorticoid receptor (GR). [J] . Schafer EA, Venkatachari NJ, Ayyavoo V Antiviral Research . 2006,第3期

机译：米非司酮对人类1型免疫缺陷病毒（HIV-1）的抗病毒作用：靶向Vpr及其细胞伴侣糖皮质激素受体（GR）。
2. The HIV-1 Vpr and glucocorticoid receptor complex is a gain-of-function interaction that prevents the nuclear localization of PARP-1 [J] . Muthumani K, Choo AY, Zong WX, Nature cell biology . 2006,第2期

机译：HIV-1 Vpr和糖皮质激素受体复合物是一种功能获得的相互作用，可阻止PARP-1的核定位
3. HIV-1 Vpr enhances production of receptor of activated NF-kappaB ligand (RANKL) via potentiation of glucocorticoid receptor activity. [J] . Fakruddin JM, Laurence J Archives of virology . 2005,第1期

机译：HIV-1 Vpr通过增强糖皮质激素受体活性来增强活化的NF-κB配体（RANKL）受体的产生。
4. Detection of Differentially Expressed Genes in Wild Type HIV-1 Vpr and Two HIV-1 Mutant Vprs [C] . Bandana Barman, Anirban Mukhopadhyay International Conference on Frontiers of Intelligent Computing : Theory and Applications . 2014

机译：在野生型HIV-1VPR和两个HIV-1突变VPRS中检测差异表达基因
5. Activation of the DNA-damage responsive signaling by HIV-1 Vpr, roles of ATR and Chk1 and implications for HIV-1 replication and pathogenesis. [D] . Roshal, Mikhail. 2003

机译：HIV-1 Vpr对DNA损伤应答信号的激活，ATR和Chk1的作用以及对HIV-1复制和发病机制的影响。
6. The glucocorticoid receptor type II complex is a target of the HIV-1 vpr gene product. [O] . Y Refaeli, D N Levy, D B Weiner 1995

机译：II型糖皮质激素受体复合物是HIV-1 vpr基因产物的靶标。
7. The glucocorticoid receptor type II complex is a target of the HIV-1 vpr gene product. [O] . Refaeli, Y, Levy, D N, Weiner, D B 1995

机译：II型糖皮质激素受体复合物是HIV-1 vpr基因产物的靶标。

The glucocorticoid receptor type Ⅱ complex is a target of the HIV-1 vpr gene product

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