Respiratory Viruses That Hijack Immune Mechanisms May Have Achilles’ Heel

A viral protein, NSD of respiratory syncytial virus (RSV), could provide information to deter pneumonia causing the body’s exaggerated inflammatory response to respiratory viruses, including the virus that causes COVID-19, new study results show.¹

The findings of the recent study conducted at Washington State University’s (WSU) College of Veterinary Medicine and published in MBio, show that if the virus lacks this protein, the human body’s immune response can destroy the virus before exaggerated inflammation begins.¹

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 to make 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.¹

“Exaggerated inflammation clogs the airways and makes breathing difficult,” Kim Chiok, PhD, a post-doctoral researcher associate at WSU and led the study, said in a statement. “This is why people who have these long-term and severe inflammatory responses get pneumonia and need help breathing, and it’s why they end up in the hospital in the [intensive care unit].”¹

The investigators are laying the framework to break that cycle by understanding how respiratory viruses, like RSV, persist in the cell.¹

RVS is affects about 64 million individuals globally and can causes 160,000 deaths annually, according to the National Institute of Allergies and Infectious Diseases.²

RSV causes 160,000 deaths annually primarily in children, the elderly, immune-compromised individuals, and infants, according to National Institute of Allergy and Infectious Diseases.² Investigators conducted the study in a laboratory at the WSU’s Veterinary Microbiology and Pathology research unit. They first determined the viral proteins’ functions by using viruses lacking genes that code for different viral proteins and comparing them with a wild strain of the virus.¹

“The virus has a series of tools, some tools with multiple functions, we wanted to learn about these tools by essentially taking them away,” Chiok said.¹

Each tool is a different viral protein.¹

Investigators identified the viral NS2 protein as a key regulator of autophagy, a cellular process that modulates immune defense during virus infection. Autophagy is meditated by a cellular protein known as Beclin1.¹

When the virus enters the cell, Beclin1 recognizes and clears the threat from the cell by attaching to smaller gene proteins through a process known as ISGylation.¹

Chiok describes this as Beclin1 putting on a suit of armor.¹

The study results show that RSV’s NS2 protein removes the “armor” from Belclin1, which allows the virus to persist and replicate within the cell and then spreading to other cells and causing damage that initiates an exaggerated inflammatory response from the body that culminates in airway diseases, such as pneumonia.¹

Without the NS2 protein, the virus is destroyed by Beclin1.¹

“In a way, you are disabling NS2’s ability to modulate the cell’s immune defense mechanism,” Chiok said.¹ “You can use therapeutics to target that protein and potentially transfer this concept to other respiratory viruses like influenza A virus and SARS-CoV-2.”

The study was funded by a grant from the National Institutes of Health.¹

References

1. Respiratory viruses that hijack immune mechanisms may have Achilles’ heel. EurekAlert. News release. January 18, 2022. Accessed January 18, 2022. https://www.eurekalert.org/news-releases/940269

2. Respiratory syncytial virus (RSV). National Institute of Allergy and Infectious Diseases. Updated December 12, 2008. Accessed January 18, 2022. https://www.niaid.nih.gov/diseases-conditions/respiratory-syncytial-virus-rsv