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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.

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.
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https://hal-pasteur.archives-ouvertes.fr/pasteur-02017878
Contributor : Marie Martin <>
Submitted on : Wednesday, February 13, 2019 - 2:09:54 PM
Last modification on : Saturday, October 3, 2020 - 4:21:48 AM

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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⟩

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