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@ARTICLE{Pastorio:281522,
      author       = {Pastorio, Chiara and Richard, Khumoekae and Usmani, Shariq
                      and Kissmann, Ann-Kathrin and Bolotnikov, Grigory and
                      Gosálbez, Guillermo and Hayn, Manuel and Koepke, Lennart
                      and Sauertnik, Alina and Preising, Andrea and Preising, Nico
                      and Ständker, Ludger and Fair, Matthew and Morris,
                      Jessicamarie and Papasavvas, Emmanouil and Liu, Qin and Sun,
                      Honghong and Rodríguez, Armando and Mounzer, Karam and
                      Wiese, Sebastian and Tebas, Pablo and Du, Yangzhu and Laird,
                      Gregory M and Jaritz, Markus and Rosenau, Frank and Gaidt,
                      Moritz M and Sparrer, Konstantin M J and Montaner, Luis J
                      and Kirchhoff, Frank},
      title        = {{R}etinol {B}inding {P}rotein 4 reactivates latent {HIV}-1
                      by triggering canonical {NF}-κ{B}, {JAK}/{STAT}5 and {JNK}
                      signalling.},
      journal      = {Signal transduction and targeted therapy},
      volume       = {10},
      number       = {1},
      issn         = {2095-9907},
      address      = {London},
      publisher    = {Macmillan Publishers, part of Springer Nature},
      reportid     = {DZNE-2025-01140},
      pages        = {326},
      year         = {2025},
      abstract     = {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.},
      keywords     = {Humans / HIV-1: genetics / HIV-1: pathogenicity / NF-kappa
                      B: genetics / Virus Latency: genetics / HIV Infections:
                      genetics / HIV Infections: virology / Retinol-Binding
                      Proteins, Plasma: genetics / Retinol-Binding Proteins,
                      Plasma: metabolism / Virus Activation: genetics / STAT5
                      Transcription Factor: genetics / Janus Kinases: genetics /
                      MAP Kinase Signaling System: genetics / NF-kappa B (NLM
                      Chemicals) / Retinol-Binding Proteins, Plasma (NLM
                      Chemicals) / RBP4 protein, human (NLM Chemicals) / STAT5
                      Transcription Factor (NLM Chemicals) / Janus Kinases (NLM
                      Chemicals)},
      cin          = {AG Sparrer},
      ddc          = {610},
      cid          = {I:(DE-2719)1910003},
      pnm          = {351 - Brain Function (POF4-351)},
      pid          = {G:(DE-HGF)POF4-351},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:41038866},
      pmc          = {pmc:PMC12491451},
      doi          = {10.1038/s41392-025-02424-3},
      url          = {https://pub.dzne.de/record/281522},
}