Gelsolin segment 5 inhibits HIV-induced T-cell apoptosis via Vpr-binding to VDAC
Gelsolin segment 5 inhibits HIV-induced T-cell apoptosis via Vpr-binding to VDAC
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DOI：
10.1016/j.febslet.2006.12.057
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发表时间：
2007-02-06
期刊：
影响因子：
3.5
通讯作者：
McMillan, James R.
中科院分区：
文献类型：
--
作者：
Qiao, Hongjiang;McMillan, James R.
来自人类免疫缺陷病毒的病毒蛋白 R (Vpr) 可诱导增殖细胞的细胞周期停滞，刺激病毒转录，并调节受感染 T 淋巴细胞的激活和凋亡。我们报告过表达全长凝溶胶蛋白的 Jurkat 细胞对 Vpr 诱导的 T 细胞凋亡具有抵抗力，并消除了线粒体膜电位损失和细胞色素 c 的释放。 HEK293T 细胞中的免疫共沉淀测定表明，全长或片段 5 (G5) 的过表达而非 G5 缺失的凝溶胶蛋白 (AG5) 与电压依赖性阴离子通道 (VDAC) 结合，并且 G5 亚基可以抑制 HIV-1-Vpr 与 VDAC 的结合。我们还证实全长凝溶胶蛋白在 Jurkat 细胞中具有相同的作用。克隆形成分析表明，转染 G5 而不是 AG5 cDNA 可以保护 Jurkat T 细胞免受 HIV-Vpr-Tet 诱导的 T 细胞凋亡并促进细胞存活，全长凝溶胶蛋白也是如此。这些结果表明，凝溶胶蛋白 G5 结构域通过阻断 Vpr 和 VDAC 之间的相互作用来抑制 HIV-Vpr 诱导的 T 细胞凋亡，并且可能用作针对 HIV-Vpr 诱导的 T 细胞凋亡的保护性治疗。 (c) 2007 年欧洲生化学会联合会。由 Elsevier B.V. 出版。保留所有权利。
Viral protein R (Vpr) from the human immunodeficiency virus induces cell cycle arrest in proliferating cells, stimulates virus transcription, and regulates activation and apoptosis of infected T-lymphocytes. We report that Jurkat cells overexpressing full-length gelsolin show resistance to Vpr-induced T-cell apoptosis with abrogation of mitochondrial membrane potential loss and the release of cytochrome c. Co-immunoprecipitation assays in HEK293T cells demonstrated that overexpression of full-length or segment 5 (G5) but not G5-deleted gelsolin (AG5) bound to the voltage-dependent anion channel (VDAC), and that the G5 subunit can inhibit HIV-1-Vpr-binding to VDAC. We also confirmed that full-length gelsolin has the same effect in Jurkat cells. Clonogenic analysis showed that transfection of G5 but not AG5 cDNA protects Jurkat T cells from HIV-Vpr-Tet induced T-cell apoptosis and promoted cell survival, as did full-length gelsolin. These results suggest that the gelsolin G5 domain inhibits HIV-Vpr-induced T-cell apoptosis by blocking the interaction between Vpr and VDAC, and might be used as a protective treatment against HIV-Vpr-induced T-cell apoptosis. (c) 2007 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.