Mechanism of HIV-1 viral protein R-induced apoptosis

Karuppiah Muthumani, Andrew Y. Choo, Daniel S. Hwang, Michael A. Chattergoon, Nathanael N. Dayes, Donghui Zhang, Mark D. Lee, Umaheswar Duvvuri, David B. Weiner

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)583-592
Number of pages10
JournalBiochemical and Biophysical Research Communications
Volume304
Issue number3
DOIs
StatePublished - May 9 2003
Externally publishedYes

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Keywords

  • AIF
  • Apoptosis
  • Caspase
  • Cytochrome c
  • HIV-1 Vpr
  • Mitochondrial membrane potential
  • NF-κB

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Muthumani, K., Choo, A. Y., Hwang, D. S., Chattergoon, M. A., Dayes, N. N., Zhang, D., Lee, M. D., Duvvuri, U., & Weiner, D. B. (2003). Mechanism of HIV-1 viral protein R-induced apoptosis. Biochemical and Biophysical Research Communications, 304(3), 583-592. https://doi.org/10.1016/S0006-291X(03)00631-4