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

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 m...

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Detalles Bibliográficos
Autores principales: Swingler, Simon, Mann, Angela M, Zhou, Jin, Swingler, Catherine, Stevenson, Mario
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2007
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2323301/
https://www.ncbi.nlm.nih.gov/pubmed/17907802
http://dx.doi.org/10.1371/journal.ppat.0030134
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author Swingler, Simon
Mann, Angela M
Zhou, Jin
Swingler, Catherine
Stevenson, Mario
author_facet Swingler, Simon
Mann, Angela M
Zhou, Jin
Swingler, Catherine
Stevenson, Mario
author_sort Swingler, Simon
collection PubMed
description 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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spelling pubmed-23233012008-04-18 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 PLoS Pathog Research Article 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. Public Library of Science 2007-09 2007-09-28 /pmc/articles/PMC2323301/ /pubmed/17907802 http://dx.doi.org/10.1371/journal.ppat.0030134 Text en © 2007 Swingler et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
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
title Apoptotic Killing of HIV-1–Infected Macrophages Is Subverted by the Viral Envelope Glycoprotein
title_full Apoptotic Killing of HIV-1–Infected Macrophages Is Subverted by the Viral Envelope Glycoprotein
title_fullStr Apoptotic Killing of HIV-1–Infected Macrophages Is Subverted by the Viral Envelope Glycoprotein
title_full_unstemmed Apoptotic Killing of HIV-1–Infected Macrophages Is Subverted by the Viral Envelope Glycoprotein
title_short Apoptotic Killing of HIV-1–Infected Macrophages Is Subverted by the Viral Envelope Glycoprotein
title_sort apoptotic killing of hiv-1–infected macrophages is subverted by the viral envelope glycoprotein
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2323301/
https://www.ncbi.nlm.nih.gov/pubmed/17907802
http://dx.doi.org/10.1371/journal.ppat.0030134
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