New Protein Pathway Identified in HIV Latency, Aids Treatment Evasion

A new study published in Cell Reports on October 24, 2026, has identified a protein pathway that helps HIV remain hidden within the body despite ongoing treatment. Current HIV medicines are effective at suppressing the virus in the bloodstream, but HIV can persist in a dormant, or "asleep," state within certain immune cells and in the brain. These hidden pockets, known as HIV reservoirs, are the primary reason a complete cure remains elusive with today's treatments.

Waqas Ahmed, Ph.D., a postdoctoral scholar at the UNC HIV Cure Center and the Department of Biochemistry & Biophysics, stated that the study reveals how human proteins contribute to maintaining HIV dormancy. He noted that the research identifies a pathway that could be targeted in future cure efforts, bringing scientists closer to strategies for eliminating persistent HIV.

Dr. Guochun Jiang, the corresponding author and part of the research team, along with his colleagues, discovered that three human proteins—ENL, USP7, and BRD4—collaborate to maintain HIV latency, effectively keeping the virus quiet and concealed. When researchers disrupted either ENL or USP7, they successfully reactivated latent HIV in peripheral blood and brain immune cells, specifically microglia, which were isolated from individuals with HIV undergoing antiretroviral therapy.

Ahmed's next research phase will involve further studying this newly identified pathway to understand its mechanisms and to evaluate the safety and effectiveness of targeting ENL or USP7. Researchers are also keen to gain a deeper understanding of how these pathways function across various cell types, particularly within the brain. Dr. Jiang emphasized that targeting the ENL–USP7–BRD4 pathway provides a novel approach to disrupt hidden HIV reservoirs as part of a broader cure strategy, potentially guiding the development of future methods aimed at eliminating these persistent reservoirs.

Beyond HIV research, the findings also hold significant translational potential for cancer therapy. Given that BRD4 is a key oncogenic driver in multiple cancers, the discovery could inform future cancer research by targeting USP7 for degradation, thereby eliminating the BRD4 protein.

What to watch: Further studies on the safety and effectiveness of targeting this protein pathway for HIV eradication.

Editor's note: Excellent synthesis of the research findings, the specific protein pathway, and the potential implications for both HIV and cancer therapy.