Identification of RBP4 as an enhancer of latent HIV.
Researchers at Ulm University Hospital have identified a method to reactivate latent HIV viruses using the body’s own RBP4 protein, a vitamin A transporter. This discovery offers a novel avenue for developing potential HIV cure strategies. The director of the Institute of Molecular Virology at Ulm University Hospital, Professor Frank Kirchhoff explained that the team have discovered a natural active substance that can ‘startle’ ‘hidden’ HI viruses, rendering them susceptible to the immune system.The natural active agent is the retinol-binding protein RBP4.Kirchhoff coordinated the study, which was recently published in Signal Transduction and Targeted Therapy.
An international research team, including scientists from the U.S., Vienna, and Ulm, conducted a comprehensive screening of the human blood peptidome to identify proteins and peptides capable of reactivating latent HIV. Using a model of latently infected T lymphocytes, they demonstrated that RBP4-mediated latency reversal is also effective in cells from HIV-positive individuals with undetectable viral loads under long-term therapy. Notably, physiological concentrations of RBP4 naturally present in the body were sufficient to awaken dormant viruses.
The researchers found that only RBP4 bound to retinol can reactivate latent HIV; the unloaded protein, retinol, or retinoic acid alone are ineffective. Successful reactivation requires activation of the NF-κB signaling pathway, a key regulator of immune and cell-division processes, which is enhanced by additional signals.
Image Credit: Signal Transduction and Targeted Therapy (2025). DOI: 10.1038/s41392-025-02424-3 (MedicalXpress)
