Mitochondrial Apoptosis Induced by the HIV-1 Envelope

Maria Castedo, Jean Luc Perfettini, Karine Andreau, Thomas Roumier, Mauro Piacentini, Guido Kroemer

Research output: Contribution to journalArticlepeer-review

Abstract

The envelope glycoprotein complex (Env), encoded by the human immunodeficiency virus (HIV-I), kills uninfected cells expressing CD4 and/or the chemokine receptor CXCR4 or CCR5, via at least three independent mechanisms. First, the soluble Env product gp120 can induce the apoptotic cell death of lymphocytes, neurons, and myocardiocytes, via interaction with surface receptors. Second, Env present on the surface of HIV-1 infected cells can transiently interact with cells expressing CD4 and CXCR4/CCRS, thereby provoking a hemifusion event that results in the death of the uninfected cell. Third, the interaction between Env on infected cells and its receptors on uninfected cells can result in syncytium formation. Such syncytia undergo apoptosis after a phase of latency. In several models of Env-induced apoptosis, early signs of mitochondrial membrane permeabilization (MMP) become manifest. Such signs include a loss of the mitochondrial transmembrane potential and the release of cytochrome c and AIF. The mechanisms of Env-triggered apoptotic MMP may involve an elevation of cytosolic Ca2+, reactive oxygen species and/ or the transcriptional activation of p53, with the consequent expression of proapoptotic proteins such as Bax, which permeabilizes mitochondrial membranes. The implications of these findings for the pathophysiology of HIV-1 infection is discussed.

Original languageEnglish
Pages (from-to)19-28
Number of pages10
JournalAnnals of the New York Academy of Sciences
Volume1010
DOIs
Publication statusPublished - 2003

Keywords

  • AIDS
  • Human immunodeficiency virus
  • Mitochondrial transmembrane potential
  • p53
  • Programmed cell death

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • History and Philosophy of Science

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