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Glycolysis downregulation is a hallmark of HIV-1 latency and sensitizes infected cells to oxidative stress

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...

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Hauptverfasser: Shytaj, Iart Luca (VerfasserIn) , Procopio, Francesco Andrea (VerfasserIn) , Tarek, Mohammad (VerfasserIn) , Carlon-Andres, Irene (VerfasserIn) , Tang, Hsin-Yao (VerfasserIn) , Goldman, Aaron R. (VerfasserIn) , Munshi, MohamedHusen (VerfasserIn) , Kumar Pal, Virender (VerfasserIn) , Forcato, Mattia (VerfasserIn) , Sreeram, Sheetal (VerfasserIn) , Leskov, Konstantin (VerfasserIn) , Ye, Fengchun (VerfasserIn) , Lucic, Bojana (VerfasserIn) , Cruz, Nicolly (VerfasserIn) , Ndhlovu, Lishomwa C. (VerfasserIn) , Bicciato, Silvio (VerfasserIn) , Padilla-Parra, Sergi (VerfasserIn) , Diaz, Ricardo Sobhie (VerfasserIn) , Singh, Amit (VerfasserIn) , Lusic, Marina (VerfasserIn) , Karn, Jonathan (VerfasserIn) , Alvarez-Carbonell, David (VerfasserIn) , Savarino, Andrea (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 20 July 2021
In: EMBO molecular medicine
Year: 2021, Jahrgang: 13, Heft: 8, Pages: 1-20
ISSN:1757-4684
DOI:10.15252/emmm.202013901
Online-Zugang:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.15252/emmm.202013901
Volltext
Verfasserangaben:Iart Luca Shytaj, Francesco Andrea Procopio, Mohammad Tarek, Irene Carlon-Andres, Hsin-Yao Tang, Aaron R. Goldman, MohamedHusen Munshi, Virender Kumar Pal, Mattia Forcato, Sheetal Sreeram, Konstantin Leskov, Fengchun Ye, Bojana Lucic, Nicolly Cruz, Lishomwa C. Ndhlovu, Silvio Bicciato, Sergi Padilla-Parra, Ricardo Sobhie Diaz, Amit Singh, Marina Lusic, Jonathan Karn, David Alvarez-Carbonell & Andrea Savarino
Beschreibung
Zusammenfassung: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.
Beschreibung:Gesehen am 27.01.2022
Beschreibung:Online Resource
ISSN:1757-4684
DOI:10.15252/emmm.202013901

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