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) , Véronique Avettand-Fénoêl (1) , Faroudy Boufassa (4) , Marc Sitbon (5) , Olivier Lambotte (6, 3) , Maria-Isabel Thoulouze (7) , Michaela Müller-Trutwin (1) , Nicolas Chomont (8) , Asier Saez-Cirion (1)

1 HIV, Inflammation et persistance - HIV, Inflammation and Persistence
2 Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB
3 Service de Médecine Interne et Immunologie clinique [AP-HP Hôpital Bicêtre]
4 CESP - Centre de recherche en épidémiologie et santé des populations
5 IGMM - Institut de Génétique Moléculaire de Montpellier
6 IMVA - U1184 - Immunologie des Maladies Virales et Autoimmunes
7 Virologie Structurale - Structural Virology
8 CHUM - Centre Hospitalier de l'Université de Montréal

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

Domains: Life Sciences [q-bio]; Microbiology and Parasitology; Virology; Life Sciences [q-bio]; Immunology

Jose Carlos Valle-Casuso, Mathieu Angin, Stevenn Volant, Caroline Passaes, Valerie Monceaux, et al.. Cellular Metabolism Is a Major Determinant of HIV-1 Reservoir Seeding in CD4+ T Cells and Offers an Opportunity to Tackle Infection.. Cell Metabolism, 2018, 29 (3), pp.611-626.e5. ⟨10.1016/j.cmet.2018.11.015⟩. ⟨pasteur-02017878⟩