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
in English
| MEDLINE | ID: covidwho-1346766
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.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
HIV Infections
/
HIV-1
Limits:
Humans
Language:
English
Journal:
EMBO Mol Med
Journal subject:
Molecular Biology
Year:
2021
Document Type:
Article
Affiliation country:
Emmm.202013901
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