Mechanism of HIV-1 viral protein R-induced apoptosis.
The paradigm of HIV-1 infection includes the diminution of CD4(+) T cells, loss of immune function, and eventual progression to AIDS. However, the mechanisms that drive host T cell depletion remain elusive. One HIV protein thought to participate in this destructive cascade is the Vpr gene product. Accordingly, we review the biology of the HIV-1 viral protein R (Vpr) an apoptogenic HIV-1 accessory protein that is packaged into the virus particle. In this review we focus specifically on Vpr's ability to induce host cell apoptosis. Recent evidence suggests that Vpr implements a unique mechanism to drive host cell apoptosis, by directly depolarizing the mitochondria membrane potential. Vpr's attack on the mitochondria results in release of cytochrome c resulting in activation of the caspase 9 pathway culminating in the activation of caspase 3 and the downstream events of apoptosis. Vpr may interact with the adenine nucleotide translocator (ANT) to prompt this cascade. The role of Vpr-induced apoptosis in HIV pathogenesis is considered.
Muthumani
Karuppiah
K
Department of Pathology and Laboratory Medicine, University of Pennsylvania, 505 Stellar Chance Laboratories, 422 Curie Boulevard, Philadelphia, PA 19104, USA.
Choo
Andrew Y
AY
Hwang
Daniel S
DS
Chattergoon
Michael A
MA
Dayes
Nathanael N
NN
Zhang
Donghui
D
Lee
Mark D
MD
Duvvuri
Umaheswar
U
Weiner
David B
DB
D017209:Apoptosis; D020169:Caspases / Q000378:metabolism; D002453:Cell Cycle; D016336:Gene Products, vpr / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D015497:HIV-1 / Q000472:pathogenicity*; D006801:Humans; D008564:Membrane Potentials; D008928:Mitochondria / Q000502:physiology; D008954:Models, Biological; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000166:cytology / Q000378:metabolism / Q000821:virology; D054325:vpr Gene Products, Human Immunodeficiency Virus
D016336:Gene Products, vpr; D016328:NF-kappa B; D054325:vpr Gene Products, Human Immunodeficiency Virus; D020169:Caspases