Promising target for HIV treatment identified

Like a slumbering dragon, HIV can lay dormant in a person's cells for years, evading medical treatments only to wake up and strike at a later time, quickly replicating itself and destroying the immune system.

Now, scientists at the Salk Institute for Biological Studies have uncovered a new protein that participates in active HIV replication.

The protein, called Ssu72, is part of a switch used to awaken HIV-1 (the most common type of HIV) from its slumber.

The team began by identifying a list of 50 or so proteins that interact with a well-known protein HIV creates called Tat.

"The virus cannot live without Tat," said Katherine Jones, Salk professor in the Regulatory Biology Laboratory and senior author of the study.

Tat acts as a lookout in the cell for the virus, telling the virus when the cellular environment is favourable for its replication.

When the environment is right, Tat kicks off the virus' transcription, the process by which HIV reads and replicates its building blocks (RNA) to spread throughout the body.

One of the proteins on the list that caught Jones' eye was Ssu72 (a phosphatase).

This enzyme had been shown in yeast to affect the transcription machinery. Her team found that Ssu72 binds directly to Tat and not only begins the transcription process, but also creates a feedback loop to ramp up the process.

"Tat is like an engine for HIV replication and Ssu72 revs up the engine," said Lirong Zhang, one of the first authors.

"If we target this interaction between Ssu72 and Tat, we may be able to stop the replication of HIV," said Zhang.

The team found that Ssu72 is not required for making RNA for most host cell genes in the way it is used by HIV, making it a potentially promising target for drug therapy.

"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 co-first author Yupeng Chen, a Salk researcher.

"Ssu72 seems to be different - at least in the way it is used by HIV," said Chen.

The study was published in the journal Genes and Development.