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| Verfasst von: | Shytaj, Iart Luca [VerfasserIn]  |
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| | Procopio, Francesco Andrea [VerfasserIn] |
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| | Tarek, Mohammad [VerfasserIn] |
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| | Carlon-Andres, Irene [VerfasserIn] |
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| | Tang, Hsin-Yao [VerfasserIn] |
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| | Goldman, Aaron R. [VerfasserIn] |
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| | Munshi, MohamedHusen [VerfasserIn] |
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| | Kumar Pal, Virender [VerfasserIn] |
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| | Forcato, Mattia [VerfasserIn] |
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| | Sreeram, Sheetal [VerfasserIn] |
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| | Leskov, Konstantin [VerfasserIn] |
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| | Ye, Fengchun [VerfasserIn] |
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| | Lucic, Bojana [VerfasserIn] |
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| | Cruz, Nicolly [VerfasserIn] |
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| | Ndhlovu, Lishomwa C. [VerfasserIn] |
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| | Bicciato, Silvio [VerfasserIn] |
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| | Padilla-Parra, Sergi [VerfasserIn] |
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| | Diaz, Ricardo Sobhie [VerfasserIn] |
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| | Singh, Amit [VerfasserIn] |
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| | Lusic, Marina [VerfasserIn] |
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| | Karn, Jonathan [VerfasserIn] |
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| | Alvarez-Carbonell, David [VerfasserIn] |
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| | Savarino, Andrea [VerfasserIn] |
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| Titel: | Glycolysis downregulation is a hallmark of HIV-1 latency and sensitizes infected cells to oxidative stress |
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| Verf.angabe: | 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 |
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| E-Jahr: | 2021 |
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| Jahr: | 20 July 2021 |
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| Umfang: | 20 S. |
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| Fussnoten: | Gesehen am 27.01.2022 |
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| Titel Quelle: | Enthalten in: European Molecular Biology OrganizationEMBO molecular medicine |
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| Ort Quelle: | Weinheim : Wiley-VCH, 2009 |
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| Jahr Quelle: | 2021 |
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| Band/Heft Quelle: | 13(2021), 8, Artikel-ID e13901, Seite 1-20 |
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| ISSN Quelle: | 1757-4684 |
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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. |
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| DOI: | doi:10.15252/emmm.202013901 |
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| URL: | Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.
Volltext: https://doi.org/10.15252/emmm.202013901 |
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| | DOI: https://doi.org/10.15252/emmm.202013901 |
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| Datenträger: | Online-Ressource |
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| Sprache: | eng |
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| Sach-SW: | CD4-Positive T-Lymphocytes |
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| | Down-Regulation |
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| | glycolysis |
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| | Glycolysis |
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| | HIV Infections |
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| | HIV-1 |
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| | HIV-1 latency |
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| | Humans |
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| | oxidative stress |
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| | Oxidative Stress |
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| | pentose cycle |
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| | Proteomics |
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| | pyrimidine metabolism |
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| | Virus Activation |
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| | Virus Latency |
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| K10plus-PPN: | 1787346668 |
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| Verknüpfungen: | → Zeitschrift |
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Glycolysis downregulation is a hallmark of HIV-1 latency and sensitizes infected cells to oxidative stress / Shytaj, Iart Luca [VerfasserIn]; 20 July 2021 (Online-Ressource)
