UNC researchers find protein pathway that keeps HIV hidden despite treatment

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Researchers at the University of North Carolina have identified how three human proteins work together to keep HIV dormant inside immune cells, a finding that could open a new route toward flushing out the hidden virus that current treatments cannot reach.

The study, published in Cell Reports, found that ENL, USP7 and BRD4 cooperate to maintain HIV latency. When the researchers disrupted ENL or USP7, they were able to reactivate latent HIV in peripheral blood and in microglia, the brain's immune cells, taken from people with HIV who are on antiretroviral therapy.

The result matters because of why HIV cannot yet be cured. Today's medicines suppress the virus in the blood effectively, but HIV can remain asleep inside certain immune cells and in the brain. Those hidden pockets, called reservoirs, are the main reason treatment must continue for life.

The university's account is the primary source for the finding, and the paper itself, by Waqas Ahmed and colleagues in the lab of Guochun Jiang at the UNC HIV Cure Center, is cited with its journal and DOI. One boundary is stated plainly by the researchers themselves: reactivating latent virus in the laboratory is not a cure, and the next step is to study whether targeting ENL or USP7 is safe and effective.

The pathway may reach beyond HIV. Because BRD4 drives several cancers, Jiang said the discovery has potential for cancer therapy too, through targeting USP7 for degradation and thereby eliminating BRD4 protein.

For now, the work is a roadmap rather than a treatment. It gives cure researchers a specific protein complex to probe, in blood and in the brain, where reservoirs have been hardest to study.