Researchers from the Salk Institute have discovered a previously unknown component of HIV’s life cycle that’s crucial to drive the production of new viral particles inside infected cells. Because it plays such an essential role in the virus’ replication process, the discoverers believe that targeting it could present a novel way to stop the virus from making new copies of itself. The work has been published in Genes & Development.
HIV, or human immunodeficiency virus, is the causative agent of acquired immune deficiency syndrome (AIDS). The virus has 9 genes which produce proteins that fall into three categories: structural, accessory and regulatory. Together, these are responsible for establishing the sophisticated interactions between the virus and host cells, which are predominantly members of the immune system.
It’s well-established that one of the regulatory proteins, called Tat, is critical for the efficient replication of the virus. Although it has many different functions, it’s primarily involved in altering the expression of viral genes. It carries out this important role by kick starting a phase called transcription, which is a process that involves generating blueprints, or RNA molecules, for new viral components.
It’s known that Tat interacts with lots of different things in the cell, but scientists are still continuing to unravel its important partners. In this latest study, Salk scientists scrutinized infected cells and identified some 50 cellular proteins that were found to interact with Tat. After probing the proteins, they discovered that one in particular was important for its function. This was an enzyme, or biological catalyst, called Ssu72 that had been previously found to affect the transcription machinery inside yeast cells.
Further investigation revealed that Ssu72 sticks directly to Tat, a critical step in the initiation of viral transcription. Furthermore, in doing so, a feedback loop is generated that cranks up the whole process, making viral gene expression more efficient.
“Tat is like an engine for HIV replication and Ssu72 revs up the engine,” study author Lirong Zhang said in a news-release. “If we target this interaction between Ssu72 and Tat, we may be able to stop the replication of HIV.”
It’s not always possible to target cellular proteins because many play important roles that are essential to the health of the cell. Furthermore, many of Tat’s partners are needed for expression of our own genes. However, Ssu72 was found to not be required for transcription of the majority of cellular genes, suggesting it could be a promising antiviral target.
The researchers are therefore taking their work further by investigating possible ways to target the interaction between Tat and Ssu72. If successful, it might be possible to translate these findings into new drug therapies.
