March 4, 2024

Influenza A virus is one of the most persistent and contagious viruses in the world. Researchers have just discovered how it thrives by slicing and dicing the genetic material inside our cells while keeping itself intact. The discovery could open up a new avenue to fight the virus.

According to the World Health OrganizationInfluenza causes three to five million severe cases each year, with 290,000 to 650,000 deaths from respiratory complications.

The two main viruses that cause influenza—influenza A and influenza B— has been around for centuries And, while some antiviral advances have been made, these bacteria have proven extremely difficult to eradicate. Now, researchers at the University of Wisconsin-Madison (UW-Madison) have uncovered at least one of the secrets to influenza A’s success, a discovery that may give researchers another way to fight the virus.

The discovery hinges on how the virus uses a protein called PA-X to make numerous cuts into the host cell’s RNA without damaging its own RNA.

host off

When the flu virus uses this protein to cleave RNA in the host, it prevents RNA from performing one of its key roles in infection — triggering the immune system to fight the flu virus. It also allows the virus to take over the host cell and create copies of itself in a process called host shutdown. Yet, somehow, the protein does not affect the virus’s own RNA.

The researchers found that the RNA sequences targeted by PA-X were extremely specific. In fact, it’s abundant in humans and other virus-susceptible animals, but it’s barely found in the virus’s own RNA.

If researchers can learn to block PA-X with such scalpel-like precision, they may come up with a tool to help bolster our defenses against influenza A.

flip the script

The UW-Madison findings shed further light on a previously unseen ability in viruses, self/non-self recognition. It refers to the mechanism by which the virus distinguishes its own RNA from that of the host. While it’s the other way around — host cells are able to distinguish themselves from viruses — knowing that viruses themselves can do this is new information.

“It’s interesting that the virus also found a way to do this, flipping the script,” said lead author Marta Gaglia, an associate professor of medical microbiology and immunology at UW-Madison.

The team plans to continue focusing on PA-X and hopes to elucidate how the protein and RNA sequences it acts on can help identify stronger and weaker flu strains.

“The ideal world we’re hoping to achieve is: If you give me a sequence, I can look at it and say, ‘This is a very active version,’ or ‘This is a less active version,'” said Gallia . “In simple terms, this could indicate whether it might be a more dangerous strain.”

The research has been published in the journal natural microbiology.

source: University of Wisconsin-Madison