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000281522 1001_ $$00000-0002-4745-3678$$aPastorio, Chiara$$b0
000281522 245__ $$aRetinol Binding Protein 4 reactivates latent HIV-1 by triggering canonical NF-κB, JAK/STAT5 and JNK signalling.
000281522 260__ $$aLondon$$bMacmillan Publishers, part of Springer Nature$$c2025
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000281522 520__ $$aReactivation of the latent viral reservoirs is crucial for a cure of HIV/AIDS. However, current latency reversing agents are inefficient, and the endogenous factors that have the potential to reactivate HIV in vivo remain poorly understood. To identify natural activators of latent HIV-1, we screened a comprehensive peptide/protein library derived from human hemofiltrate, representing the entire blood peptidome, using J-Lat cell lines harboring transcriptionally silent HIV-1 GFP reporter viruses. Fractions potently reactivating HIV-1 from latency contained human Retinol Binding Protein 4 (RBP4), the carrier of retinol (Vitamin A). We found that retinol-bound holo-RBP4 but not retinol-free apo-RBP4 strongly reactivates HIV-1 in a variety of latently infected T cell lines. Functional analyses indicate that this reactivation involves activation of the canonical NF-κB pathway and is strengthened by JAK/STAT5 and JNK signalling but does not require retinoic acid production. High levels of RBP4 were detected in plasma from both healthy individuals and people living with HIV-1. Physiological concentrations of RBP4 induced significant viral reactivation in latently infected cells from individuals on long-term antiretroviral therapy with undetectable viral loads. As a potent natural HIV-1 latency-reversing agent, RBP4 offers a novel approach to activating the latent reservoirs and bringing us closer to a cure.
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000281522 650_7 $$2NLM Chemicals$$aNF-kappa B
000281522 650_7 $$2NLM Chemicals$$aRetinol-Binding Proteins, Plasma
000281522 650_7 $$2NLM Chemicals$$aRBP4 protein, human
000281522 650_7 $$2NLM Chemicals$$aSTAT5 Transcription Factor
000281522 650_7 $$0EC 2.7.10.2$$2NLM Chemicals$$aJanus Kinases
000281522 650_2 $$2MeSH$$aHumans
000281522 650_2 $$2MeSH$$aHIV-1: genetics
000281522 650_2 $$2MeSH$$aHIV-1: pathogenicity
000281522 650_2 $$2MeSH$$aNF-kappa B: genetics
000281522 650_2 $$2MeSH$$aVirus Latency: genetics
000281522 650_2 $$2MeSH$$aHIV Infections: genetics
000281522 650_2 $$2MeSH$$aHIV Infections: virology
000281522 650_2 $$2MeSH$$aRetinol-Binding Proteins, Plasma: genetics
000281522 650_2 $$2MeSH$$aRetinol-Binding Proteins, Plasma: metabolism
000281522 650_2 $$2MeSH$$aVirus Activation: genetics
000281522 650_2 $$2MeSH$$aSTAT5 Transcription Factor: genetics
000281522 650_2 $$2MeSH$$aJanus Kinases: genetics
000281522 650_2 $$2MeSH$$aMAP Kinase Signaling System: genetics
000281522 7001_ $$aRichard, Khumoekae$$b1
000281522 7001_ $$aUsmani, Shariq$$b2
000281522 7001_ $$aKissmann, Ann-Kathrin$$b3
000281522 7001_ $$aBolotnikov, Grigory$$b4
000281522 7001_ $$aGosálbez, Guillermo$$b5
000281522 7001_ $$aHayn, Manuel$$b6
000281522 7001_ $$aKoepke, Lennart$$b7
000281522 7001_ $$aSauertnik, Alina$$b8
000281522 7001_ $$aPreising, Andrea$$b9
000281522 7001_ $$aPreising, Nico$$b10
000281522 7001_ $$aStändker, Ludger$$b11
000281522 7001_ $$aFair, Matthew$$b12
000281522 7001_ $$aMorris, Jessicamarie$$b13
000281522 7001_ $$aPapasavvas, Emmanouil$$b14
000281522 7001_ $$aLiu, Qin$$b15
000281522 7001_ $$aSun, Honghong$$b16
000281522 7001_ $$00000-0001-5921-3770$$aRodríguez, Armando$$b17
000281522 7001_ $$aMounzer, Karam$$b18
000281522 7001_ $$aWiese, Sebastian$$b19
000281522 7001_ $$00000-0001-5345-7942$$aTebas, Pablo$$b20
000281522 7001_ $$aDu, Yangzhu$$b21
000281522 7001_ $$aLaird, Gregory M$$b22
000281522 7001_ $$00000-0002-9326-2047$$aJaritz, Markus$$b23
000281522 7001_ $$aRosenau, Frank$$b24
000281522 7001_ $$aGaidt, Moritz M$$b25
000281522 7001_ $$0P:(DE-2719)9003481$$aSparrer, Konstantin M J$$b26
000281522 7001_ $$00000-0001-5799-6759$$aMontaner, Luis J$$b27
000281522 7001_ $$00000-0002-7052-2360$$aKirchhoff, Frank$$b28
000281522 773__ $$0PERI:(DE-600)2886872-9$$a10.1038/s41392-025-02424-3$$gVol. 10, no. 1, p. 326$$n1$$p326$$tSignal transduction and targeted therapy$$v10$$x2095-9907$$y2025
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