HIV-infected macrophages and microglia that survive acute infection become viral reservoirs by a mechanism involving Bim

Paul Castellano, Lisa Prevedel, Eliseo Eugenin

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

While HIV kills most of the cells it infects, a small number of infected cells survive and become latent viral reservoirs, posing a significant barrier to HIV eradication. However, the mechanism by which immune cells resist HIV-induced apoptosis is still incompletely understood. Here, we demonstrate that while acute HIV infection of human microglia/macrophages results in massive apoptosis, a small population of HIV-infected cells survive infection, silence viral replication, and can reactivate viral production upon specific treatments. We also found that HIV fusion inhibitors intended for use as antiretroviral therapies extended the survival of HIV-infected macrophages. Analysis of the pro-and anti-apoptotic pathways indicated no significant changes in Bcl-2, Mcl-1, Bak, Bax or caspase activation, suggesting that HIV blocks a very early step of apoptosis. Interestingly, Bim, a highly pro-apoptotic negative regulator of Bcl-2, was upregulated and recruited into the mitochondria in latently HIV-infected macrophages both in vitro and in vivo. Together, these results demonstrate that macrophages/microglia act as HIV reservoirs and utilize a novel mechanism to prevent HIV-induced apoptosis. Furthermore, they also suggest that Bim recruitment to mitochondria could be used as a biomarker of viral reservoirs in vivo.

Original languageEnglish (US)
Article number12866
JournalScientific Reports
Volume7
Issue number1
DOIs
StatePublished - Dec 1 2017
Externally publishedYes

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Microglia
Virus Diseases
Macrophages
HIV
Apoptosis
Mitochondria
HIV Fusion Inhibitors
Caspases
HIV Infections
Cell Count
Biomarkers
Survival

ASJC Scopus subject areas

  • General

Cite this

HIV-infected macrophages and microglia that survive acute infection become viral reservoirs by a mechanism involving Bim. / Castellano, Paul; Prevedel, Lisa; Eugenin, Eliseo.

In: Scientific Reports, Vol. 7, No. 1, 12866, 01.12.2017.

Research output: Contribution to journalArticle

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