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...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
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Springer
2021
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| _version_ | 1826315029747597312 |
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| author | Shytaj, IL Procopio, FA Tarek, M Carlon‐Andres, I Tang, H Goldman, AR Munshi, M Kumar Pal, V Forcato, M Sreeram, S Leskov, K Ye, F Lucic, B Cruz, N Ndhlovu, LC Bicciato, S Padilla‐Parra, S Diaz, RS Singh, A Lusic, M Karn, J Alvarez‐Carbonell, D Savarino, A |
| author_facet | Shytaj, IL Procopio, FA Tarek, M Carlon‐Andres, I Tang, H Goldman, AR Munshi, M Kumar Pal, V Forcato, M Sreeram, S Leskov, K Ye, F Lucic, B Cruz, N Ndhlovu, LC Bicciato, S Padilla‐Parra, S Diaz, RS Singh, A Lusic, M Karn, J Alvarez‐Carbonell, D Savarino, A |
| author_sort | Shytaj, IL |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-12-09T03:16:50Z |
| format | Journal article |
| id | oxford-uuid:7148d203-13a4-4160-89bd-8f6f092e672d |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-12-09T03:16:50Z |
| publishDate | 2021 |
| publisher | Springer |
| record_format | dspace |
| spelling | oxford-uuid:7148d203-13a4-4160-89bd-8f6f092e672d2024-10-24T20:15:17ZGlycolysis downregulation is a hallmark of HIV‐1 latency and sensitizes infected cells to oxidative stressJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:7148d203-13a4-4160-89bd-8f6f092e672dEnglishJisc Publications RouterSpringer2021Shytaj, ILProcopio, FATarek, MCarlon‐Andres, ITang, HGoldman, ARMunshi, MKumar Pal, VForcato, MSreeram, SLeskov, KYe, FLucic, BCruz, NNdhlovu, LCBicciato, SPadilla‐Parra, SDiaz, RSSingh, ALusic, MKarn, JAlvarez‐Carbonell, DSavarino, AHIV‐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. |
| spellingShingle | Shytaj, IL Procopio, FA Tarek, M Carlon‐Andres, I Tang, H Goldman, AR Munshi, M Kumar Pal, V Forcato, M Sreeram, S Leskov, K Ye, F Lucic, B Cruz, N Ndhlovu, LC Bicciato, S Padilla‐Parra, S Diaz, RS Singh, A Lusic, M Karn, J Alvarez‐Carbonell, D Savarino, A Glycolysis downregulation is a hallmark of HIV‐1 latency and sensitizes infected cells to oxidative stress |
| title | Glycolysis downregulation is a hallmark of HIV‐1 latency and sensitizes infected cells to oxidative stress |
| title_full | Glycolysis downregulation is a hallmark of HIV‐1 latency and sensitizes infected cells to oxidative stress |
| title_fullStr | Glycolysis downregulation is a hallmark of HIV‐1 latency and sensitizes infected cells to oxidative stress |
| title_full_unstemmed | Glycolysis downregulation is a hallmark of HIV‐1 latency and sensitizes infected cells to oxidative stress |
| title_short | Glycolysis downregulation is a hallmark of HIV‐1 latency and sensitizes infected cells to oxidative stress |
| title_sort | glycolysis downregulation is a hallmark of hiv 1 latency and sensitizes infected cells to oxidative stress |
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