APOPTOTIC KILLING OF HIV-1-INFECTED MACROPHAGES IS SUBVERTED BY THE VIRAL ENVELOPE GLYCOPROTEIN.

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

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

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Viruses have evolved strategies Cardigans 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 Chipset Cooling Fan 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.

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