Respiratory viruses that "hijack" immune mechanisms may have a fatal weakness

According to the latest paper published in the authoritative journal "mBio" in the field of microbial research on the 18th, researchers at the School of Veterinary Medicine of Washington State University in the United States found a respiratory syncytial virus (RSV) protein called NS2. If the virus lacks this protein, the body's immune response can destroy it before excessive inflammation begins.

Like respiratory viruses such as covid-19, RSV infects lung cells responsible for gas exchange and uses them as "factories" to make more viruses. The uncontrollable proliferation of viruses in these cells can lead to severe lung disease and even death.

Kim Jock, a postdoctoral researcher at Washington State University who led the study, said excessive inflammation blocks the airways and makes it difficult to breathe, which is why patients end up in the ICU.

According to the National Institute of Allergy and Infectious Diseases, RSV kills 160,000 people each year, mostly infants, children, the elderly and immunocompromised people.

The RSV virus has a series of "tools," each of which is a different viral protein, some with multiple functions, Chork said.

To understand how respiratory viruses, such as RSV, persist within cells, the researchers first used viruses that lacked genes that code for different viral proteins and compared them to wild strains of the virus to determine the function of viral proteins.

Jock found that the viral NS2 protein is a key regulator of autophagy. Autophagy is a cellular process that regulates immune defenses during viral infection. Autophagy is mediated by a cellular protein called Beclin1.

When the virus enters the cell, Beclin1 can recognize and clear the threat from the cell. It does this through a process called ISGization that attaches to certain smaller genetic proteins. It's almost like beclin 1 wearing a suit of armor, Jock said.

Studies have shown that RSV's NS2 protein removes the "armor" of Beclin1, enabling the virus to persist and replicate within cells and spread to other cells causing damage, triggering an excessive inflammatory response from the body and ultimately leading to respiratory diseases such as pneumonia. Without the NS2 protein, the virus is usually destroyed by Beclin1.

Joker said that using therapeutic agents that target the NS2 viral protein can somehow undermine the protein's ability to regulate the cellular immune defense mechanisms. In the future, it is also possible to shift this idea to target other respiratory viruses, such as influenza A virus and the new crown virus. (Intern reporter Zhang Jiaxin)

Source: Science and Technology Daily