A big issue associated with finding a cure for HIV is that it can remain latent and hide in cells for many years. Researchers are exploring two main strategies to tackle this problem—reactivate and destroy the latent virus (called "shock and kill") or find a way to silence it for good. To tackle both strategies, scientists from the Gladstone Institutes discovered how a new drug called JQ1, which is currently in early-phase cancer trials, can reactivate latent HIV. This work was published today in the journal Molecular Cell.
"We already knew that the drug JQ1 targets a protein called BRD4, but our experiments were not yielding consistent results. Then, we started looking at different forms of the protein and, unexpectedly, found that a short form was the key to silencing HIV," explains senior investigator, Melanie Ott.
By identifying this new role for the short form of BRD4, Ott's team could finally explain a mechanism that controls HIV latency. They showed that the drug JQ1 targets and removes the short form of BRD4, which then allows the virus to make copies of itself.
Many scientists concentrate on the "shock and kill" strategy as a way to cure HIV, but more and more of them are shifting their focus to silencing the virus. The mechanism discovered at Gladstone can support both strategies—manipulating the BRD4 protein either to help HIV resurface or to strengthen the body's capacity to suppress it.
This strategy could potentially allow patients to stop taking drugs, and for several years to elapse before the virus reactivates. By that time, the immune system could be strong enough to eliminate the virus as it surfaces.
The team is now focused on finding a way to target the virus so people who are infected can stop continuously taking pills.