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Breakthrough in HIV research: New protein activates latent viruses!
New research at Ulm University discovers mechanism for activating latent HIV viruses using RBP4, a key protein.
Breakthrough in HIV research: New protein activates latent viruses!
New research from Ulm University Hospital is bringing a breath of fresh air to the fight against HIV by discovering a groundbreaking method for activating latent HIV viruses. According to a report from Ulm University, human immunodeficiency viruses (HIV) can enter a latent state, allowing them to evade the body's immune defenses. The research group, led by Professor Frank Kirchhoff, has identified the protein RBP4, a transporter for vitamin A, as the key to activating these dormant viruses. The results have been published in the journal “Signal Transduction and Targeted Therapy”.
The international collaboration included scientists from the USA, Vienna and Ulm who examined the effects of RBP4 on HIV-infected T lymphocytes, which both carry viral genetic material and act as immune cells. The study shows that RBP4 activates latency reversal even in cells from HIV-positive individuals with undetectable viral loads. Physiological concentrations of RBP4 were sufficient to reactivate latent viruses. Interestingly, only retinol-loaded RBP4 could trigger this activation; the unloaded protein was not effective.
Latent virus activation details
The researchers undertook a detailed analysis of the human blood peptidome to test its activating effects on hidden HIV. In a sophisticated process, RBP4 was obtained from different sources and used in experiments on latent HIV infections. A model cell line for HIV-infected T lymphocytes was used to measure the effects.
In addition, the scientists demonstrated that neither retinol nor retinoic acid alone was sufficient to activate latent HIV variants. Rather, the activation of a special signaling pathway (NF-κB) was crucial for success. This suggests that future therapies that focus on the “shock-and-kill” strategy may be designed more effectively to eliminate latent viruses.
Research context and challenges
Latent reservoirs continue to represent a significant barrier to the complete cure of HIV infections. Antiretroviral therapies (ART) can suppress active replication of the virus and reduce viral load to undetectable levels. However, they are unable to directly attack the latent HIV-infected cells. This may result in a flare-up of the disease if therapy is discontinued. The research aims to develop safe and effective methods to eliminate these latent reservoirs.
Current studies address the mechanisms that control the establishment and maintenance of HIV latency and the challenges posed by these reservoirs. Animal models are also being used to study HIV latency, with ongoing efforts to combine different healing approaches to provide safe, effective and scalable therapy for the millions of people living with HIV worldwide.