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

Shytaj, IL and Procopio, FA and Tarek, M and Carlon-Andres, I and Tang, H-Y and Goldman, AR and Munshi, M and Kumar Pal, V and Forcato, M and Sreeram, S and Leskov, K and Ye, F and Lucic, B and Cruz, N and Ndhlovu, LC and Bicciato, S and Padilla-Parra, S and Diaz, RS and Singh, A and Lusic, M and Karn, J and Alvarez-Carbonell, D and Savarino, A (2021) Glycolysis downregulation is a hallmark of HIV-1 latency and sensitizes infected cells to oxidative stress. In: EMBO Molecular Medicine .

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Official URL: https://doi.org/10.15252/emmm.202013901


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. © 2021 The Authors. Published under the terms of the CC BY 4.0 license

Item Type: Journal Article
Publication: EMBO Molecular Medicine
Publisher: John Wiley and Sons Inc
Additional Information: The copyright for this article belongs to Authors
Department/Centre: Division of Biological Sciences > Microbiology & Cell Biology
Division of Biological Sciences > Centre for Infectious Disease Research
Date Deposited: 07 Oct 2021 15:57
Last Modified: 07 Oct 2021 15:57
URI: http://eprints.iisc.ac.in/id/eprint/69682

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