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

Jose Carlos Valle-Casuso; Mathieu Angin; Stevenn Volant; Caroline Passaes; Valerie Monceaux; Anastassia Mikhailova; Katia Bourdic; Veronique Avettand-Fenoel; Faroudy Boufassa; Marc Sitbon; Olivier Lambotte; Maria-Isabel Thoulouze; Michaela Müller-Trutwin; Nicolas Chomont; Asier Saez-Cirion

doi:10.1016/j.cmet.2018.11.015

Journal articles

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

Jose Carlos Valle-Casuso ¹ Mathieu Angin ¹ Stevenn Volant ² Caroline Passaes ¹ Valerie Monceaux ¹ Anastassia Mikhailova ¹ Katia Bourdic ³ Veronique Avettand-Fenoel ^{4, 5} Faroudy Boufassa ⁶ Marc Sitbon ⁷ Olivier Lambotte ^{3, 8} Maria-Isabel Thoulouze ⁹ Michaela Müller-Trutwin ¹ Nicolas Chomont ¹⁰ Asier Saez-Cirion ^{1, *}

* Corresponding author

1 HIV, Inflammation et persistance

2 Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB

3 Service de Médecine Interne et Immunologie clinique [AP-HP Hôpital Bicêtre]

4 Laboratoire de Virologie [CHU Necker]

5 UPD5 - Université Paris Descartes - Paris 5

6 CESP - Centre de recherche en épidémiologie et santé des populations

7 IGMM - Institut de Génétique Moléculaire de Montpellier

8 IMVA - U1184 - Immunologie des Maladies Virales et Autoimmunes

9 Virologie Structurale

10 CHUM - Centre Hospitalier de l'Université de Montréal

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

Domain :

Life Sciences [q-bio] / Microbiology and Parasitology / Virology

Life Sciences [q-bio] / Immunology

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

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

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