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Respiratory viruses that hijack immune mechanisms may have Achilles heel

influenza A
Transmission electron micrograph of influenza A virus, late passage. Credit: CDC

One viral protein could provide information to deter pneumonia that causes the body's excessive inflammatory response to respiratory viruses, including the virus that causes COVID-19.

The viral protein is NS2 from Respiratory Syncytial Virus (RSV), and a study has found that if the virus lacks this protein, the human body's immune response can destroy the virus before excessive inflammation begins. The research, conducted at Washington State University's College of Veterinary Medicine, was published Jan. 18 in the journal mBio.

Like other respiratory viruses, including the COVID-19-causing SARS-CoV-2 virus, RSV infects the lung cells responsible for exchanging gases and uses them as factories to produce more viruses. Uncontrollable virus multiplication in these cells leads to their destruction and manifestation of severe inflammation; lung diseases such as pneumonia; and sometimes death.

"Excessive inflammation clogs the airways and makes it difficult to breathe," said Kim Chiok, a WSU post-doc researcher who led the study. "That's why people who have these prolonged and severe inflammatory reactions get pneumonia and need help breathing, and that's why they end up in the hospital in the intensive care unit."

Chiok and other WSU researchers are setting the stage for breaking this cycle by understanding how respiratory viruses, such as RSV, continue in the cell. RSV causes 160,000 deaths annually, primarily in infants, children, the elderly and immunocompromised individuals, according to the National Institute of Allergy and Infectious Diseases.

The research was conducted in the laboratory by Professor Santanu Bose, who is part of the WSU's Veterinary Microbiology and Pathology research unit. Chiok, a Fulbright Fellow from Peru who completed his Ph.D. at WSU, has spent the last two and a half years in the Bose lab exploring the mechanisms that regulate the virus-host battle.

The researchers first determined the functions of viral proteins by using viruses lacking genes that encode different viral proteins, and comparing them to a wild-type strain of the virus.

"The virus has a number of tools, some tools with multiple functions, we wanted to learn about these tools by essentially taking them away," Chiok said.

Each tool is a different viral protein.

Chiok identified the viral NS2 protein as a key regulator of autophagy, a cellular process that modulates the immune system during viral infection. Autophagy is mediated by a cellular protein known as Beclin1.

Once the virus enters the cell, Beclin1 can recognize and remove the threat from the cell. It does this by binding to certain smaller gene proteins through a process known as ISGylation. It's almost as if Beclin1 is putting on armor, Chiok said.

The study showed that RSV's NS2 protein removes this "armor" from Beclin1, which allows the virus to persist and replicate inside the cell, spreading to other cells and causing damage that triggers an excessive inflammatory response from the body that culminates in respiratory diseases such as pneumonia. Without the NS2 protein, the virus is routinely destroyed by Beclin1.

"In a way, you disable NS2's ability to modulate the cell's immune system," Chiok said. "You can use therapy to target that protein and potentially transmit this concept to other respiratory viruses such as influenza A virus and SARS-CoV-2."

How cells defend themselves against influenza A virus

More information: Human respiratory syncytial virus NS2 protein induces autophagy by modulating Beclin1 protein stabilization and ISGylation, mBio, 2022. DOI: 10.1128 / race.03528-21
Journal information: mBio
Provided by Washington State University

Citation: Respiratory virus that hijacks immune mechanisms may have Achilles heel (2022, January 18) Retrieved January 18, 2022 from

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