Researchers Identify Protein Crucial in HIV Replication

Discovery offers potential target for future HIV treatments.

The discovery of a new protein that participates in active HIV replication may provide a target for future drug therapies.

Researchers from the Salk Institute identified the protein, called Ssu72, which participates in active HIV replication. In a study published in a recent issue of Genes & Development, Ssu72 was found to be part of a switch that activates HIV-1 from its slumber.

The team initially identified approximately 50 proteins that interact with Tat, a protein that is created by HIV.

"Many proteins that Tat interacts with are essential for normal cellular transcription so those can't be targeted unless you want to kill normal cells," said study co-first author Yupeng Chen in a press release. "Ssu72 seems to be different -- at least in the way it is used by HIV."

Tat acts as a signal to alert the virus when the cellular environment is favorable to begin replicating by starting the process where HIV reads and replicates RNA to spread throughout the body.

The Ssu72 enzyme was found to bind directly to Tat, which begins transcription and starts the feedback loop to accelerate the process, the authors noted.

Tat was previously believed to play a simpler role in the process, after prior research led scientists to believe that the CycT1 protein was used by Tat to begin replicating the virus.

"After all these years, we thought that Tat only had this one partner (CycT1), but when we looked at it a bit harder, we found that it also binds and stimulates the Ssu72 phosphatase, which controls an immediately preceding step to switch on HIV," said study lead author Katherine Jones in a press release.

While CycT1 may not present an ideal target for anti-viral treatments because it’s needed for normal cellular function, researchers noted that Ssu72 may instead provide a promising target for drug therapy.

Armed with the knowledge that Ssu72 is specifically required for HIV transcription, future studies will examine how the protein can be targeted by restricting its ability to start the transcription process.

"Tat is like an engine for HIV replication and Ssu72 revs up the engine," Lirong Zhang, one of the first authors, said in a press release. "If we target this interaction between Ssu72 and Tat, we may be able to stop the replication of HIV."