Glycolysis downregulation is a hallmark of HIV-1 latency and sensitizes infected cells to oxidative stress. Academic Article uri icon

Overview

abstract

  • HIV-1 infects lymphoid and myeloid cells, which can harbor a latent proviral reservoir responsible for maintaining lifelong infection. Glycolytic metabolism has been identified as a determinant of susceptibility to HIV-1 infection, but its role in the development and maintenance of HIV-1 latency has not been elucidated. By combining transcriptomic, proteomic, and metabolomic analyses, we here show that transition to latent HIV-1 infection downregulates glycolysis, while viral reactivation by conventional stimuli reverts this effect. Decreased glycolytic output in latently infected cells is associated with downregulation of NAD+ /NADH. Consequently, infected cells rely on the parallel pentose phosphate pathway and its main product, NADPH, fueling antioxidant pathways maintaining HIV-1 latency. Of note, blocking NADPH downstream effectors, thioredoxin and glutathione, favors HIV-1 reactivation from latency in lymphoid and myeloid cellular models. This provides a "shock and kill effect" decreasing proviral DNA in cells from people living with HIV/AIDS. Overall, our data show that downmodulation of glycolysis is a metabolic signature of HIV-1 latency that can be exploited to target latently infected cells with eradication strategies.

publication date

  • July 20, 2021

Research

keywords

  • HIV Infections
  • HIV-1

Identity

PubMed Central ID

  • PMC8350904

Scopus Document Identifier

  • 85110666076

Digital Object Identifier (DOI)

  • 10.1080/15548627.2021.1874134

PubMed ID

  • 34289240

Additional Document Info

volume

  • 13

issue

  • 8