Apoptotic Killing of HIV-1–Infected Macrophages Is Subverted by the Viral Envelope Glycoprotein

PLoS Pathogens

Jin Zhou¹  Simon Swingler¹  Catherine Swingler¹  Mario Stevenson¹  Angela M Mann¹ 

[1] Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America

关键词: Macrophages;    Apoptosis;    HIV-1;    T cells;    Flow cytometry;    Enzyme-linked immunoassays;    Viral envelope;    Cytokines;   

DOI  :  10.1371/journal.ppat.0030134

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY