Newly identified protein pathway helps HIV stay hidden despite treatment

Newly identified protein pathway helps HIV stay hidden despite treatment Swati Mestri Scientific Editor Robert Egan Senior Editor Current HIV medicines are effective at suppressing the virus in the blood. However, HIV can remain "asleep" or dormant inside certain immune cells and in the brain. These hidden pockets of virus, called HIV reservoirs, are the main reason HIV cannot be cured with today's treatments. Key proteins in HIV latency "Our study reveals how human proteins help keep HIV dormant and identifies a pathway that may be targeted in future cure research. Understanding these mechanisms brings us closer to developing strategies to eliminate persistent HIV," said Waqas Ahmed, Ph.D., a postdoctoral scholar in the lab of Guochun Jiang, Ph.D., at the UNC HIV Cure Center and the Department of Biochemistry & Biophysics. In a study published in Cell Reports, Jiang and his research team found that three human proteins—ENL, USP7 and BRD4—work together to maintain HIV latency, keeping the virus quiet and hidden. When researchers disrupted ENL or USP7, they were able to reactivate latent HIV in peripheral blood and brain immune cells called microglia, isolated from people with HIV who are on antiretroviral therapy. The next step Ahmed's next step is to study the newly identified pathway to see how it works and to evaluate whether targeting ENL or USP7 is safe and effective. Researchers also want a better understanding of how these pathways function in different cell types, particularly in the brain. "Targeting the ENL–USP7–BRD4 pathway offers a new way to disrupt hidden HIV reservoirs as part of a broader cure strategy. This research could help guide the development of future strategies aimed at eliminating HIV reservoirs that persist despite effective treatment," said Jiang, who is also the corresponding author. Impact on future treatment This study shows how human proteins help HIV hide, giving scientists a roadmap to develop strategies that expose and eliminate reservoirs that persist. Researchers also note that because BRD4 plays an important role in several cancers, these findings could inform future cancer research. "Because BRD4 is a key oncogenic driver in multiple cancers, our discovery has significant translational potential for cancer therapy by targeting USP7 for degradation, thereby eliminating BRD4 protein," said Jiang. Publication details Waqas Ahmed et al., The ENL-USP7 complex regulates HIV latency through BRD4 protein stabilization, Cell Reports (2026). DOI: 10.1016/j.celrep.2026.118120 Journal information: Cell Reports