Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2003 Dec;1010:19-28.
doi: 10.1196/annals.1299.004.

Mitochondrial Apoptosis Induced by the HIV-1 Envelope

Affiliations
Review

Mitochondrial Apoptosis Induced by the HIV-1 Envelope

Maria Castedo et al. Ann N Y Acad Sci. .

Abstract

The envelope glycoprotein complex (Env), encoded by the human immunodeficiency virus (HIV-1), 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/CCR5, 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 Ca(2+), reactive oxygen species and/or the transcriptional activation of p53, with the consequent expression of pro-apoptotic proteins such as Bax, which permeabilizes mitochondrial membranes. The implications of these findings for the pathophysiology of HIV-1 infection is discussed.

Similar articles

See all similar articles

Cited by 21 articles

See all "Cited by" articles

Publication types

LinkOut - more resources

Feedback