Abstract
The HIV-1 pandemic is a significant challenge to the field of medicine. Despite advancements in antiretroviral (ART) development, 38 million people worldwide still live with this disease without a cure. A significant barrier to the eradication of HIV-1 lies in the persistently latent pool that establishes early in the infection. The “shock and kill” strategy relies on the discovery of a latency-reversing agent (LRA) that can robustly reactivate the latent pool and not limit immune clearance. We have found that a benzodiazepine (BDZ), that is commonly prescribed for panic and anxiety disorder, to be an ideal candidate for latency reversal. The BDZ Alprazolam functions as an inhibitor of the transcription factor RUNX1, which negatively regulates HIV-1 transcription. In addition to the displacement of RUNX1 from the HIV-1 5′LTR, Alprazolam potentiates the activation of STAT5 and its recruitment to the viral promoter. The activation of STAT5 in cytotoxic T cells may enable immune activation which is independent of the IL-2 receptor. These findings have significance for the potential use of Alprazolam in a curative strategy and to addressing the neuroinflammation associated with neuroHIV-1.
Highlights
HIV-1, the causative agent of AIDS, is a retrovirus that has infected ∼38 million people worldwide [1]
Despite the effectiveness of ART, HIV-1 infection has been associated with defects in cytokine production and while SAHA, a promising latency-reversing agent (LRA), demonstrates reactivating potential for latent transcription, the negative impact HDACi impose on the CTL response does not align with the objective of eradicating the HIV-1 reservoir [15,16,17]
Our data suggest that Alprazolam may have additional utility due to the activation and recruitment of Signal Transducer and activator 5 (STAT5) to the HIV-1 long terminal repeat (LTR) while SAHA negatively impacts the recruitment of STAT5
Summary
HIV-1, the causative agent of AIDS, is a retrovirus that has infected ∼38 million people worldwide [1]. One of the main targets of HIV-1 is CD4+ T cells. The vast majority of these target cells support replication of the virus. During this productive infection, the 5’long terminal repeat (LTR) of the HIV-1 genome acts as an inducible promoter within the host chromatin to drive viral transcription [4, 5]. In a small portion of infected cells, HIV1 remains non-productive and transcriptionally silent, the viral genome persists stably in the host chromatin, and latent transcription allows the infected cell to dodge immune surveillance and its cytopathic fate [4, 6,7,8]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
