Breakthrough in HIV Cure Strategy: Key Protein Revives Hidden Virus Reservoirs

Recent research from the University of Hong Kong has identified a crucial gene transcription factor, BRD9, that plays a significant role in the persistence of HIV-1 within immune cells. Despite decades of ongoing efforts, HIV-1 remains a major health challenge due to its ability to hide in a dormant state, making it resistant to standard treatments like antiretroviral therapy (ART). The study demonstrates that targeting BRD9 can effectively reactivate latent HIV-1, a vital step in the 'shock and kill' approach aimed at eradicating the virus.

By screening 280 epigenetic compounds, researchers found that inhibiting BRD9 significantly promotes the reactivation of inactive HIV-1. The selective inhibitor I-BRD9, along with BRD9 degraders, effectively induced viral gene expression in infected T cells and primary cells from patients on ART. Notably, the inhibition of BRD9 not only reactivates HIV but also competes with the viral Tat protein, which is essential for viral transcription, thereby modulating the reactivation process.

The study also uncovered that BRD9 interacts with other cellular targets such as ATAD2 and MTHFD2, which are involved in the regulation of HIV latency. When combined with other latency reversal agents, BRD9 inhibitors exhibited a strong synergistic effect, significantly boosting the reactivation of dormant HIV reservoirs. This discovery deepens the understanding of HIV latency mechanisms and offers promising avenues for developing more effective, targeted therapies.

Professor Chen Zhiwei emphasizes that, "the persistent presence of latent HIV in immune cells remains the main obstacle to a cure. Our findings suggest that targeting host factors like BRD9 could revolutionize current treatment strategies, bringing us closer to eradicating HIV." The research highlights the potential of combining BRD9 inhibitors with existing anti-HIV agents to intensify the effort of purging hidden viral reservoirs, which is essential for achieving a complete cure.

Despite improvements with ART, many individuals still harbor small, replication-competent HIV reservoirs. This study provides crucial insights into how modulation of epigenetic factors can lead to innovative therapies that activate and subsequently eliminate these reservoirs, moving closer to the ultimate goal of HIV eradication.

Source: https://medicalxpress.com/news/2025-06-key-protein-enables-strategy-hiv.html