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

101 Citations (Scopus)

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
Pages (from-to)1281-1290
Number of pages10
JournalPLoS Pathogens
Volume3
Issue number9
DOIs
StatePublished - Sep 1 2007
Externally publishedYes

Fingerprint

HIV-1
Glycoproteins
Macrophages
Macrophage Colony-Stimulating Factor
Macrophage Colony-Stimulating Factor Receptors
TNF-Related Apoptosis-Inducing Ligand Receptors
Viral Envelope Proteins
Ligands
Down-Regulation
Tumor Necrosis Factor-alpha
Apoptosis
Cytokines
Viruses
Genes
Neoplasms

ASJC Scopus subject areas

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

Cite this

Apoptotic killing of HIV-1-infected macrophages is subverted by the viral envelope glycoprotein. / Swingler, Simon; Mann, Angela M.; Zhou, Jin; Swingler, Catherine; Stevenson, Mario.

In: PLoS Pathogens, Vol. 3, No. 9, 01.09.2007, p. 1281-1290.

Research output: Contribution to journalArticle

Swingler, Simon ; Mann, Angela M. ; Zhou, Jin ; Swingler, Catherine ; Stevenson, Mario. / Apoptotic killing of HIV-1-infected macrophages is subverted by the viral envelope glycoprotein. In: PLoS Pathogens. 2007 ; Vol. 3, No. 9. pp. 1281-1290.
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