6IMVA - U1184 - Immunologie des Maladies Virales et Autoimmunes (Site de l'Hôpital de Bicêtre - Faculté de Médecine Paris Sud - 63 rue Gabriel Péri 94276 Le Kremlin-Bicêtre Cedex.
Site du CEA de Fontenay-aux-Roses - 10, route du Panorama - BP 6 - 92265 Fontenay-aux-Roses. - France)
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.
https://hal-pasteur.archives-ouvertes.fr/pasteur-02017878 Contributor : Accord Elsevier CCSDConnect in order to contact the contributor Submitted on : Friday, October 22, 2021 - 12:06:41 PM Last modification on : Wednesday, June 15, 2022 - 4:15:15 AM Long-term archiving on: : Sunday, January 23, 2022 - 7:36:10 PM
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, Elsevier, 2018, 29 (3), pp.611-626.e5. ⟨10.1016/j.cmet.2018.11.015⟩. ⟨pasteur-02017878⟩