Role of HIV Vpr as a regulator of apoptosis and an effector on bystander cells.
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.
Moon
Ho Suck
HS
Department of Genetic Engineering, Faculty of Life Science and Technology, Sungkyunkwan University, Suwon 440-746, Korea.
Yang
Joo-Sung
JS
D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D024201:Bystander Effect / Q000502:physiology*; D016336:Gene Products, vpr / Q000378:metabolism*; D006801:Humans; D007425:Intracellular Membranes; D008928:Mitochondria / Q000378:metabolism; D010539:Permeability
D051017:Apoptosis Regulatory Proteins; D016336:Gene Products, vpr