CELLULAR METABOLISM OF HIV-1 RESERVOIR SEEDING IN CD4+ T CELLS

摘要

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- susceptibility between naïve 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 (i) impaired HIV-1 infection in vitro in all CD4+ T-cell subsets, (ii) 10 decreased the viability of pre-infected cells, and (iii) precluded HIV-1 reactivation in cells from HIV-infected individuals. Our results elucidate the link between cell metabolism and HIV- infection and identify a vulnerability to tackle HIV reservoirs and infections with other pathogens.