Alprazolam Prompts HIV-1 Transcriptional Reactivation and Enhances CTL Response Through RUNX1 Inhibition and STAT5...

Area of Science:

• Virology
• Immunology
• Neuroscience

Background:

• The HIV-1 pandemic remains a global health challenge, with millions living with the virus despite antiretroviral therapy (ART).
• A major obstacle to HIV-1 eradication is the latent viral reservoir, which ART cannot eliminate.
• The 'shock and kill' strategy aims to eliminate latent HIV-1 by reactivating it and then clearing the infected cells.

Purpose of the Study:

• To identify a latency-reversing agent (LRA) capable of reactivating latent HIV-1 for immune clearance.
• To investigate the potential of benzodiazepines (BDZs) as LRAs for HIV-1 cure strategies.

Main Methods:

• Investigated the effect of the benzodiazepine Alprazolam on HIV-1 latency.
• Assessed Alprazolam's impact on the transcription factor RUNX1 and the STAT5 pathway.
• Examined the recruitment of STAT5 to the HIV-1 promoter in cytotoxic T cells.

Main Results:

• Alprazolam was identified as a potent latency-reversing agent for HIV-1.
• Alprazolam inhibits the transcription factor RUNX1, which normally suppresses HIV-1 transcription.
• Alprazolam enhances STAT5 activation and its recruitment to the viral promoter, potentially independent of the IL-2 receptor.

Conclusions:

• Alprazolam shows promise as a latency-reversing agent in the context of HIV-1 cure strategies.
• The findings suggest a potential role for Alprazolam in immune-mediated clearance of the latent HIV-1 reservoir.
• Alprazolam may also be relevant for addressing neuroinflammation in HIV-1-associated neurocognitive disorders (HAND).