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| Home > Publications Database > Retinol Binding Protein 4 reactivates latent HIV-1 by triggering canonical NF-κB, JAK/STAT5 and JNK signalling. > print |
| Home > Publications Database > Retinol Binding Protein 4 reactivates latent HIV-1 by triggering canonical NF-κB, JAK/STAT5 and JNK signalling. > print |
| 001 | 281522 | ||
| 005 | 20251030102703.0 | ||
| 024 | 7 | _ | |a 10.1038/s41392-025-02424-3 |2 doi |
| 024 | 7 | _ | |a pmid:41038866 |2 pmid |
| 024 | 7 | _ | |a pmc:PMC12491451 |2 pmc |
| 024 | 7 | _ | |a 2095-9907 |2 ISSN |
| 024 | 7 | _ | |a 2059-3635 |2 ISSN |
| 037 | _ | _ | |a DZNE-2025-01140 |
| 041 | _ | _ | |a English |
| 082 | _ | _ | |a 610 |
| 100 | 1 | _ | |a Pastorio, Chiara |0 0000-0002-4745-3678 |b 0 |
| 245 | _ | _ | |a Retinol Binding Protein 4 reactivates latent HIV-1 by triggering canonical NF-κB, JAK/STAT5 and JNK signalling. |
| 260 | _ | _ | |a London |c 2025 |b Macmillan Publishers, part of Springer Nature |
| 336 | 7 | _ | |a article |2 DRIVER |
| 336 | 7 | _ | |a Output Types/Journal article |2 DataCite |
| 336 | 7 | _ | |a Journal Article |b journal |m journal |0 PUB:(DE-HGF)16 |s 1761739235_30626 |2 PUB:(DE-HGF) |
| 336 | 7 | _ | |a ARTICLE |2 BibTeX |
| 336 | 7 | _ | |a JOURNAL_ARTICLE |2 ORCID |
| 336 | 7 | _ | |a Journal Article |0 0 |2 EndNote |
| 520 | _ | _ | |a Reactivation 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. |
| 536 | _ | _ | |a 351 - Brain Function (POF4-351) |0 G:(DE-HGF)POF4-351 |c POF4-351 |f POF IV |x 0 |
| 588 | _ | _ | |a Dataset connected to CrossRef, PubMed, , Journals: pub.dzne.de |
| 650 | _ | 7 | |a NF-kappa B |2 NLM Chemicals |
| 650 | _ | 7 | |a Retinol-Binding Proteins, Plasma |2 NLM Chemicals |
| 650 | _ | 7 | |a RBP4 protein, human |2 NLM Chemicals |
| 650 | _ | 7 | |a STAT5 Transcription Factor |2 NLM Chemicals |
| 650 | _ | 7 | |a Janus Kinases |0 EC 2.7.10.2 |2 NLM Chemicals |
| 650 | _ | 2 | |a Humans |2 MeSH |
| 650 | _ | 2 | |a HIV-1: genetics |2 MeSH |
| 650 | _ | 2 | |a HIV-1: pathogenicity |2 MeSH |
| 650 | _ | 2 | |a NF-kappa B: genetics |2 MeSH |
| 650 | _ | 2 | |a Virus Latency: genetics |2 MeSH |
| 650 | _ | 2 | |a HIV Infections: genetics |2 MeSH |
| 650 | _ | 2 | |a HIV Infections: virology |2 MeSH |
| 650 | _ | 2 | |a Retinol-Binding Proteins, Plasma: genetics |2 MeSH |
| 650 | _ | 2 | |a Retinol-Binding Proteins, Plasma: metabolism |2 MeSH |
| 650 | _ | 2 | |a Virus Activation: genetics |2 MeSH |
| 650 | _ | 2 | |a STAT5 Transcription Factor: genetics |2 MeSH |
| 650 | _ | 2 | |a Janus Kinases: genetics |2 MeSH |
| 650 | _ | 2 | |a MAP Kinase Signaling System: genetics |2 MeSH |
| 700 | 1 | _ | |a Richard, Khumoekae |b 1 |
| 700 | 1 | _ | |a Usmani, Shariq |b 2 |
| 700 | 1 | _ | |a Kissmann, Ann-Kathrin |b 3 |
| 700 | 1 | _ | |a Bolotnikov, Grigory |b 4 |
| 700 | 1 | _ | |a Gosálbez, Guillermo |b 5 |
| 700 | 1 | _ | |a Hayn, Manuel |b 6 |
| 700 | 1 | _ | |a Koepke, Lennart |b 7 |
| 700 | 1 | _ | |a Sauertnik, Alina |b 8 |
| 700 | 1 | _ | |a Preising, Andrea |b 9 |
| 700 | 1 | _ | |a Preising, Nico |b 10 |
| 700 | 1 | _ | |a Ständker, Ludger |b 11 |
| 700 | 1 | _ | |a Fair, Matthew |b 12 |
| 700 | 1 | _ | |a Morris, Jessicamarie |b 13 |
| 700 | 1 | _ | |a Papasavvas, Emmanouil |b 14 |
| 700 | 1 | _ | |a Liu, Qin |b 15 |
| 700 | 1 | _ | |a Sun, Honghong |b 16 |
| 700 | 1 | _ | |a Rodríguez, Armando |0 0000-0001-5921-3770 |b 17 |
| 700 | 1 | _ | |a Mounzer, Karam |b 18 |
| 700 | 1 | _ | |a Wiese, Sebastian |b 19 |
| 700 | 1 | _ | |a Tebas, Pablo |0 0000-0001-5345-7942 |b 20 |
| 700 | 1 | _ | |a Du, Yangzhu |b 21 |
| 700 | 1 | _ | |a Laird, Gregory M |b 22 |
| 700 | 1 | _ | |a Jaritz, Markus |0 0000-0002-9326-2047 |b 23 |
| 700 | 1 | _ | |a Rosenau, Frank |b 24 |
| 700 | 1 | _ | |a Gaidt, Moritz M |b 25 |
| 700 | 1 | _ | |a Sparrer, Konstantin M J |0 P:(DE-2719)9003481 |b 26 |
| 700 | 1 | _ | |a Montaner, Luis J |0 0000-0001-5799-6759 |b 27 |
| 700 | 1 | _ | |a Kirchhoff, Frank |0 0000-0002-7052-2360 |b 28 |
| 773 | _ | _ | |a 10.1038/s41392-025-02424-3 |g Vol. 10, no. 1, p. 326 |0 PERI:(DE-600)2886872-9 |n 1 |p 326 |t Signal transduction and targeted therapy |v 10 |y 2025 |x 2095-9907 |
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