Program in Molecular Medicine
Apoptosis; Gene Products, env; HIV Infections; *HIV-1; Humans; Macrophage Colony-Stimulating Factor; Macrophages; Piperazines; Pyrimidines; Receptors, TNF-Related Apoptosis-Inducing Ligand
Life Sciences | Medicine and Health Sciences
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.
DOI of Published Version
PLoS Pathog. 2007 Sep 7;3(9):1281-90. Link to article on publisher's site
Swingler, Simon; Mann, Angela; Zhou, Jin; Swingler, Catherine; and Stevenson, Mario, "Apoptotic killing of HIV-1-infected macrophages is subverted by the viral envelope glycoprotein" (2007). Open Access Articles. 1350.