HIV and apoptosis death and the mitochondrion.
HIV and apoptosis death and the mitochondrion.
复制标题
HIV和细胞凋亡死亡和线粒体。
DOI：
10.1084/jem.193.4.f11
复制
发表时间：
2001
期刊：
影响因子：
--
通讯作者：
Zimmerberg,J
中科院分区：
文献类型：
--
作者：
Basanez,G;Zimmerberg,J
虽然HIV-1发病机制的一个主要特征是CD4+ T细胞因凋亡而死亡，但凋亡的机制存在很大争议（1,2）。一些HIV-1蛋白与细胞凋亡调控有关，其中包括病毒蛋白R (Vpr)，这是一种小的（14 kD） HIV-1辅助蛋白，通过与Pr55 Gag前体相互作用被包裹在核衣壳中(3)。除了在细胞凋亡和病毒组装中的作用外，vpr与蛋白质的相互作用还包括：(a) HIV-1预整合复合物通过核孔易位，这是HIV-1在非分裂细胞中复制的必要步骤——vpr似乎通过与核粘蛋白α的结合参与了这一过程；(b)诱导细胞周期阻滞，可能通过Vpr结合并使MOV34失活，MOV34是p34-cyclin b复合物的上游正调节因子，对G2-M相变至关重要；(c)通过Vpr与转录因子的物理相互作用和/或其对细胞周期的影响刺激病毒基因表达。Vpr能够通过蛋白与蛋白之间的直接相互作用以及靶蛋白活性的变化来发挥如此多的作用，这可以通过将Vpr视为伴侣来解释，正如最近提出的Vpr可以替代hsp70（一种细胞伴侣）这一事实(4)。因此，Vpr似乎具有结构特征，允许以足够的能量与多个蛋白质结合，从而引起目标蛋白质活性（可能是构象）的变化。在这一期(5)中，Jacotot等人扩展了他们之前的发现(6)，即线粒体腺嘌呤核苷酸转运子（ANT），一个被提出的渗透过渡孔的组成部分，构成了一个新的Vpr靶标。在这里，他们提出了大量的实验来验证Vpr和ANT的物理相互作用是Vpr诱导细胞凋亡的核心。首先，在纯脂质双分子层膜中，他们证明了加入由Vpr （Vpr 52-96）和ANT衍生的凋亡肽可导致通道形成。他们测量的通道可以很容易地大到足以渗透（尽管通道选择性-）
While a main feature of HIV-1 pathogenesis is the death of CD4+ T cells due to apoptosis, the mechanisms of apoptosis are highly controversial (1, 2). Several HIV-1 proteins have been implicated in apoptosis regulation, among them viral protein R (Vpr), a small (14 kD) HIV-1 accessory protein that is packed in the nucleocapsid through its interaction with the Pr55 Gag precursor (3). In addition to its roles in apoptosis and virus assembly, several other activities have been ascribed to Vpr–protein interaction, including:(a) translocation of the HIV-1 preintegration complex through the nuclear pore, a necessary step for the replication of HIV-1 in nondividing cells—Vpr appears to participate in this process by binding to kariopherin α;(b) induction of cell cycle arrest, likely by Vpr binding to and inactivating MOV34, an upstream positive regulator of the p34–cyclin B complex shown to be essential for the G2–M phase transition;(c) stimulation of viral gene expression through physical interaction of Vpr with transcription factors and/or as a consequence of its effect on cell cycle. The ability of Vpr to exert so many effects through direct protein–protein interactions, followed by changes in target protein activity, can be explained by thinking of Vpr as a chaperone, as recently suggested by the fact that Vpr can substitute for hsp70, a cellular chaperone (4). Thus, Vpr seems to possess structural features that allow for binding to more than one protein with sufficient energy to cause changes in activity (presumably in conformation) of target proteins.In this issue (5), Jacotot et al. extend their previous finding (6) that the mitochondrial adenine nucleotide translocator (ANT), a proposed component of the permeability transition pore, constitutes a novel Vpr target. Here, they present a large number of experiments to test the idea that this physical interaction of Vpr and ANT is central to Vprinduced apoptosis. First, in pure lipid bilayer membranes, they demonstrate that adding an apoptogenic peptide derived from Vpr (Vpr 52–96) and ANT together leads to channel formation. The channels they measure could easily be large enough to permeabilize (although channel selectiv-