Moon Ho Suck, Yang Joo-Sung
Department of Genetic Engineering, Faculty of Life Science and Technology, Sungkyunkwan University, Suwon 440-746, Korea.
Mol Cells. 2006 Feb 28;21(1):7-20.
The major event in human immunodeficiency virus type 1 (HIV-1) infection is the death of many cells related to host immune response. The demise of these cells is normally explained by cell suicide mechanism, apoptosis. Interestingly, the decrease in the number of immune cells, such as non-CD4(+) cells as well as CD4(+) T cells, in HIV infection usually occurs in uninfected bystander cells, not in directly infected cells. It has, therefore, been suggested that several soluble factors, including viral protein R (Vpr), are released from the infected cells and induce the death of bystander cells. Some studies show that Vpr interacts directly with adenine nucleotide translocator (ANT) to induce mitochondrial membrane permeabilization (MMP). The MMP results in release of some apoptogenic factors such as cytochrome-c (cyt-c) and apoptosis-inducing factor (AIF). Vpr also has indirect effect on mitochondria through enhancing the level of caspase-9 transcription and suppressing nuclear factor-kappa B (NF-kB). The involvement of p53 in Vpr-induced apoptosis remains to be studied. On the other hand, low level of Vpr expression has anti-apoptotic effect, whereas it's high level of expression induces apoptosis. Extracellular Vpr also exhibits cytotoxicity to uninfected bystander cells through apoptotic or necrotic mechanism. The facts that Vpr has cytotoxic effect on both infected cells and bystander cells, and that it exhibits both pro- and anti-apoptotic activity may explain its role in viral survival and disease progression.
1型人类免疫缺陷病毒（HIV-1）感染中的主要事件是许多与宿主免疫反应相关的细胞死亡。这些细胞的死亡通常由细胞自杀机制即凋亡来解释。有趣的是，在HIV感染中，免疫细胞数量的减少，如非CD4(+)细胞以及CD4(+) T细胞，通常发生在未感染的旁观者细胞中，而非直接感染的细胞中。因此，有人提出包括病毒蛋白R（Vpr）在内的几种可溶性因子从感染细胞中释放出来并诱导旁观者细胞死亡。一些研究表明，Vpr直接与腺嘌呤核苷酸转位酶（ANT）相互作用以诱导线粒体膜通透性改变（MMP）。MMP导致一些凋亡诱导因子如细胞色素c（cyt-c）和凋亡诱导因子（AIF）的释放。Vpr还通过提高半胱天冬酶-9转录水平和抑制核因子-κB（NF-κB）对线粒体产生间接影响。p53在Vpr诱导的凋亡中的作用仍有待研究。另一方面，低水平的Vpr表达具有抗凋亡作用，而高水平的表达则诱导凋亡。细胞外Vpr还通过凋亡或坏死机制对未感染的旁观者细胞表现出细胞毒性。Vpr对感染细胞和旁观者细胞均具有细胞毒性作用，并且它同时具有促凋亡和抗凋亡活性，这些事实可能解释了它在病毒存活和疾病进展中的作用。
