HIV infection and latency induce a unique metabolic signature in human macrophages

Paul Castellano, Lisa Prevedel, Silvana Valdebenito, Eliseo Eugenin

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Currently, a major barrier to curing HIV infection is the generation of tissue-associated, non-replicating, long-lasting viral reservoirs that are refractory to therapy and can be reactivated upon anti-retroviral therapy interruption. One of these reservoirs are latently HIV-infected macrophages. Here, we show that HIV infection of macrophages results in survival of a small population of infected cells that are metabolically altered and characterized by mitochondrial fusion, lipid accumulation, and reduced mitochondrial ATP production. No changes in glycolysis were detected. Metabolic analysis indicated an essential role of succinate and other TCA metabolites in the tricarboxylic acid (TCA) cycle in mediating lipid accumulation and oxidative phosphorylation (OXPHOS) in the mitochondria. Furthermore, we show that while uninfected and HIV infected macrophages use fatty acids and glucose as primary sources of energy, surviving HIV infected macrophages also use glutamine/glutamate as a major energy source, and blocking these new sources of energy resulted in the killing of latent HIV infected macrophages. Together, our data provide a new understanding of the formation, properties, and potential novel ways to eliminate macrophage viral reservoirs.

Original languageEnglish (US)
Article number3941
JournalScientific reports
Volume9
Issue number1
DOIs
StatePublished - Dec 1 2019

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HIV Infections
Macrophages
HIV
Tricarboxylic Acids
Mitochondrial Dynamics
Lipids
Citric Acid Cycle
Oxidative Phosphorylation
Succinic Acid
Glycolysis
Glutamine
Glutamic Acid
Mitochondria
Fatty Acids
Adenosine Triphosphate
Glucose
Survival
Therapeutics
Population

ASJC Scopus subject areas

  • General

Cite this

HIV infection and latency induce a unique metabolic signature in human macrophages. / Castellano, Paul; Prevedel, Lisa; Valdebenito, Silvana; Eugenin, Eliseo.

In: Scientific reports, Vol. 9, No. 1, 3941, 01.12.2019.

Research output: Contribution to journalArticle

Castellano, Paul ; Prevedel, Lisa ; Valdebenito, Silvana ; Eugenin, Eliseo. / HIV infection and latency induce a unique metabolic signature in human macrophages. In: Scientific reports. 2019 ; Vol. 9, No. 1.
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