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

Simon Swingler, Angela M. Mann, Jin Zhou, Catherine Swingler, Mario Stevenson

Research output: Contribution to journalArticle

105 Scopus citations

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 languageEnglish (US)
Pages (from-to)1281-1290
Number of pages10
JournalPLoS pathogens
Volume3
Issue number9
DOIs
StatePublished - Sep 1 2007

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Molecular Biology
  • Genetics
  • Virology

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