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Cell Metab. 2018 Dec 19. pii: S1550-4131(18)30734-4. doi: 10.1016/j.cmet.2018.11.015. [Epub ahead of print]

Cellular Metabolism Is a Major Determinant of HIV-1 Reservoir Seeding in CD4+ T Cells and Offers an Opportunity to Tackle Infection.

Author information

1
Institut Pasteur, Unité HIV Inflammation et Persistance, 28 rue du Docteur Roux, 75724 Paris Cedex 15, France.
2
Institut Pasteur, Hub Bioinformatique et Biostatistique - C3BI, USR 3756 IP CNRS, Paris, France.
3
Assistance Publique Hôpitaux de Paris, Hôpital Bicêtre, Service de Médecine Interne et Immunologie Clinique, 94275 Le Kremlin-Bicêtre, France.
4
Université Paris Descartes, Sorbonne Paris Cité, 7327 Paris, France; Assistance Publique Hôpitaux de Paris, Laboratoire de Virologie, CHU Necker-Enfants Malades, Paris, France.
5
INSERM U1018, Centre de Recherche en Epidémiologie et Santé des Populations, Université Paris Sud, Le Kremlin-Bicêtre, France.
6
Institut de Génétique Moléculaire de Montpellier, University of Montpellier, CNRS, Montpellier, France.
7
Assistance Publique Hôpitaux de Paris, Hôpital Bicêtre, Service de Médecine Interne et Immunologie Clinique, 94275 Le Kremlin-Bicêtre, France; CEA, Université Paris Sud, INSERM U1184, Center for Immunology of Viral Infections and Autoimmune Diseases (IMVA), IDMIT Department/IBFJ, Fontenay-aux-Roses, France.
8
Institut Pasteur, Unité Virologie Structurale, Paris, France.
9
Centre de Recherche du CHUM and Department of Microbiology, Infectiology and Immunology, Université de Montréal, Montreal H2X 0A9, Canada.
10
Institut Pasteur, Unité HIV Inflammation et Persistance, 28 rue du Docteur Roux, 75724 Paris Cedex 15, France. Electronic address: asier.saez-cirion@pasteur.fr.

Abstract

HIV persists in long-lived infected cells that are not affected by antiretroviral treatment. These HIV reservoirs are mainly located in CD4+ T cells, but their distribution is variable in the different subsets. Susceptibility to HIV-1 increases with CD4+ T cell differentiation. We evaluated whether the metabolic programming that supports the differentiation and function of CD4+ T cells affected their susceptibility to HIV-1. We found that differences in HIV-1 susceptibility between naive and more differentiated subsets were associated with the metabolic activity of the cells. Indeed, HIV-1 selectively infected CD4+ T cells with high oxidative phosphorylation and glycolysis, independent of their activation phenotype. Moreover, partial inhibition of glycolysis (1) impaired HIV-1 infection in vitro in all CD4+ T cell subsets, (2) decreased the viability of preinfected cells, and (3) precluded HIV-1 amplification in cells from HIV-infected individuals. Our results elucidate the link between cell metabolism and HIV-1 infection and identify a vulnerability in tackling HIV reservoirs.

KEYWORDS:

CD4(+) T cell; HIV reservoir; HIV-1; T cell differentiation; cellular metabolism; glycolysis; metabolic inhibitors; oxidative phosphorylation; susceptibility to HIV-1

PMID:
30581119
DOI:
10.1016/j.cmet.2018.11.015

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