|HIV particles infecting a human T cell--Courtesy of NIH/NIAID|
HIV has proved a challenging disease for drug developers to cure, partly because of its ability to hide out in cells in a dormant state, avoiding the immune system's detection and remaining untouched by antiretroviral drugs used to treat the virus.
But dormant virus can activate at a later time, replicating and wreaking havoc in the immune system.
Now, researchers at the Salk Institute for Biological Studies have uncovered a protein that plays a role in active HIV replication, essentially acting as part of a switch to turn HIV-1, the most common type of HIV, from a dormant state to an active one. Investigators hope to harness the discovery to develop new treatments against HIV, which infects about 35 million people worldwide. Currently used antiretrovirals fail to reawaken and destroy these dormant pools of HIV, called reservoirs.
Scientists zeroed on in the new protein, called Ssu72, after identifying about 50 proteins that interact with a well-known protein HIV creates called Tat. Tat is essential to HIV's survival, acting as a lookout by telling the virus when the cellular environment looks right for replication. When Tat detects a favorable environment, the protein then kicks into gear the virus' transcription, the process by which HIV reads and replicates its RNA to spread throughout the body.
Lirong Zhang, one of the first authors and a Salk researcher, and her colleagues found that one of the proteins, an enzyme called Ssu72, was able to initiate this transcription process and created a feedback loop to scale up the process.
"Tat is like an engine for HIV replication and Ssu72 revs up the engine," Zhang said in a statement. "If we target this interaction between Ssu72 and Tat, we may be able to stop the replication of HIV."
The findings were surprising because Tat was thought to have a simpler job and only one partner, a protein called CycT1.
With the newfound knowledge, the team is now working on ways to target Ssu72 for therapeutic uses, such as inhibiting Ssu72's ability to start the transcription process.
They are also examining whether latent HIV infections result from low levels of Ssu72 in resting T cells. And stay tuned: The lab is excited about checking other new host cell partners of Tat that were identified in this study.