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 language | English |
|---|---|
| Pages (from-to) | 1281-1290 |
| Number of pages | 10 |
| Journal | PLoS Pathogens |
| Volume | 3 |
| Issue number | 9 |
| DOIs | |
| State | Published - Sep 1 2007 |
| Externally published | Yes |
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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 journal › Article
}
TY - JOUR
T1 - Apoptotic killing of HIV-1-infected macrophages is subverted by the viral envelope glycoprotein
AU - Swingler, Simon
AU - Mann, Angela M.
AU - Zhou, Jin
AU - Swingler, Catherine
AU - Stevenson, Mario
PY - 2007/9/1
Y1 - 2007/9/1
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=34848893294&partnerID=8YFLogxK
U2 - 10.1371/journal.ppat.0030134
DO - 10.1371/journal.ppat.0030134
M3 - Article
C2 - 17907802
AN - SCOPUS:34848893294
VL - 3
SP - 1281
EP - 1290
JO - PLoS Pathogens
JF - PLoS Pathogens
SN - 1553-7366
IS - 9
ER -