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

Cell Metabolism
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Valle-Casuso JC, Angin M, Volant S, Passaes C, Monceaux V, Mikhailova A, Bourdic K, Avettand-Fenoel V, Boufassa F, Sitbon M, Lambotte O, Thoulouze MI, Muller-Trutwin M, Chomont N and Saez-Cirion A.

Cell Metab. 2018 Dec 19

DOI: https://doi.org/10.1016/j.cmet.2018.11.015

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.