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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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. © 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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