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PLoS Pathog. 2007 Sep 7;3(9):1281-90.

Apoptotic killing of HIV-1-infected macrophages is subverted by the viral envelope glycoprotein.

Author information

1
Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA.

Abstract

Viruses have evolved strategies to protect infected cells from apoptotic clearance. We present evidence that HIV-1 possesses a mechanism to protect infected macrophages from the apoptotic effects of the death ligand TRAIL (tumor necrosis factor-related apoptosis-inducing ligand). In HIV-1-infected macrophages, the viral envelope protein induced macrophage colony-stimulating factor (M-CSF). This pro-survival cytokine downregulated the TRAIL receptor TRAIL-R1/DR4 and upregulated the anti-apoptotic genes Bfl-1 and Mcl-1. Inhibition of M-CSF activity or silencing of Bfl-1 and Mcl-1 rendered infected macrophages highly susceptible to TRAIL. The anti-cancer agent Imatinib inhibited M-CSF receptor activation and restored the apoptotic sensitivity of HIV-1-infected macrophages, suggesting a novel strategy to curtail viral persistence in the macrophage reservoir.

PMID:
17907802
PMCID:
PMC2323301
DOI:
10.1371/journal.ppat.0030134
[Indexed for MEDLINE]
Free PMC Article

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