Glycolysis downregulation is a hallmark of HIV-1 latency and sensitizes infected cells to oxidative stress.
Détails
Etat: Public
Version: Final published version
Licence: CC BY 4.0
ID Serval
serval:BIB_B314A864B89C
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Glycolysis downregulation is a hallmark of HIV-1 latency and sensitizes infected cells to oxidative stress.
Périodique
EMBO molecular medicine
ISSN
1757-4684 (Electronic)
ISSN-L
1757-4676
Statut éditorial
Publié
Date de publication
09/08/2021
Peer-reviewed
Oui
Volume
13
Numéro
8
Pages
e13901
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Publication Status: ppublish
Résumé
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 <sup>+</sup> /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.
Mots-clé
CD4-Positive T-Lymphocytes, Down-Regulation, Glycolysis, HIV Infections, HIV-1, Humans, Oxidative Stress, Proteomics, Virus Activation, Virus Latency, HIV-1 latency, glycolysis, oxidative stress, pentose cycle, pyrimidine metabolism
Pubmed
Web of science
Open Access
Oui
Création de la notice
26/07/2021 9:18
Dernière modification de la notice
23/01/2024 8:32