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

Cell Metab. 2019 Mar 5;29(3):611-626.e5. doi: 10.1016/j.cmet.2018.11.015. Epub 2018 Dec 20.

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.

Keywords: CD4(+) T cell; HIV reservoir; HIV-1; T cell differentiation; cellular metabolism; glycolysis; metabolic inhibitors; oxidative phosphorylation; susceptibility to HIV-1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CD4-Positive T-Lymphocytes / metabolism*
  • CD4-Positive T-Lymphocytes / pathology
  • Cell Differentiation
  • Cells, Cultured
  • Glycolysis / immunology
  • HIV Infections / metabolism*
  • HIV Infections / pathology
  • HIV-1
  • Humans
  • Lymphocyte Activation
  • Oxidative Phosphorylation
  • T-Lymphocyte Subsets / metabolism*
  • T-Lymphocyte Subsets / pathology