Glycolysis downregulation is a hallmark of HIV-1 latency and sensitizes infected cells to oxidative stress.
EMBO Mol Med
; 13(8): e13901, 2021 08 09.
Article
de En
| MEDLINE
| ID: mdl-34289240
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.
Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Infections à VIH
/
VIH-1 (Virus de l'Immunodéficience Humaine de type 1)
Limites:
Humans
Langue:
En
Journal:
EMBO Mol Med
Sujet du journal:
BIOLOGIA MOLECULAR
Année:
2021
Type de document:
Article
Pays d'affiliation:
Italie