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.
Original language | English (US) |
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Pages (from-to) | 1281-1290 |
Number of pages | 10 |
Journal | PLoS pathogens |
Volume | 3 |
Issue number | 9 |
DOIs | |
State | Published - Sep 2007 |
ASJC Scopus subject areas
- Parasitology
- Microbiology
- Immunology
- Molecular Biology
- Genetics
- Virology