The ENL-USP7 complex regulates HIV latency through BRD4 protein stabilization.

Inhibiting ENL or USP7 reactivates latent HIV and destabilizes BRD4, revealing a key host pathway maintaining HIV reservoirs in CD4+ T cells and brain microglia.

• Why it matters: HIV persistence in these cells under antiretroviral therapy poses a major obstacle to eradication, and understanding host mechanisms that sustain latency is crucial for developing cure strategies.
• What they did: The study used pharmacologic inhibitors, genetic loss, proteomic analyses, chromatin immunoprecipitation, and single-nucleus RNA sequencing to investigate the ENL-USP7-BRD4 axis, focusing on its role in latency maintenance and viral reservoir stability.
• The result: Targeting this axis through USP7 degradation or ENL loss reactivated latent HIV in resting CD4+ T cells and brain microglia, suggesting it as a promising therapeutic target for HIV cure efforts.