Pitt team finds HIV protein weakness

Researchers from the University of Pittsburgh School of Medicine may have found a unique target in a key HIV protein.

In a study published online in the journal Chemistry and Biology, the scientists showed how they could potentially target the spot to keep the virus from replicating. If successful, HIV infection might be stopped from progressing into full-blown AIDS.

The HIV protein, called Nef, interacts with other proteins in infected cells to help the virus proliferate and hide from the immune system. The Pitt team created a way to track Nef activity with high-throughput screening protocols linked to an enzyme called Hck.

"We reasoned that agents that prevent Nef from its usual interactions with other proteins might be able to stop HIV from replicating and infecting other cells," senior author Dr. Thomas Smithgall said. "For this study, we devised an automated screening procedure and tested nearly 250,000 compounds to find ones that could block Nef activity."

Additional analysis showed that a compound known as B9 could prevent Nef molecules from combining. This inability impairs Nef's function in the viral replication process.

"This pocket where B9 binds to Nef and where Nef forms a dimer indicates it's a hot spot, or Achilles heel, that could represent a new target for HIV drugs," Smithgall said. "Our test tube and cell culture experiments show that blocking this site brings HIV replication to a halt."