Protease from cold virus activates inflammasome to trigger immune response

The role of a protein in detecting the common cold virus and kickstarting an immune response to fight infection has been uncovered by a team of scientists.

In a study published in Science, they showed that the protein NLRP1, found on the skin and in the airways, is a sensor that detects the human rhinovirus (HRV). When NLRP1 breaches the respiratory tract, it triggers an immune response leading to inflammation in the lungs and causes symptoms of the common cold.

HRV is a major cause of the common cold and acute respiratory disease in children and adults, which in severe cases, leads to bronchiolitis and pneumonia.

The research team said that discovering NLRP1's purpose could lead to new treatments for the symptoms of the common cold, which affects millions of people annually. They plan to work with clinicians to develop drugs that 'turn off' or block NLRP1, to lessen the severity of symptoms for HRV-related diseases. However, the team noted that blocking the protein in human lung cells did not increase the viral load, which refers to the amount of virus in an infected person's blood.

"Now that we know that NLRP1 is the "on switch" for inflammation after it detects the common cold virus, the next step is to figure out how to block its activation and to minimise the inflammatory response it triggers," said the corresponding author.

"This work represents a significant advance in our understanding of how our immune system uses special proteins to sense and defend against viral pathogens. This knowledge will be useful in the design of treatments for viral diseases including influenza and Covid-19," the author said.

NLRP1 has been known to scientists for years but its exact purpose was unknown. It is a member of a class called 'Nod-like Receptor' proteins that are sensors in the immune system that trigger the human body's response against invading pathogens.

When the team began their study in 2017, they hypothesised that NLRP1 serves as a sensor for viruses, because it is highly abundant in the human skin and lungs - surfaces that are commonly exposed to viral pathogens.

The team screened NLRP1 against several viruses to see if any would trigger the protein. After months of trials, they observed that an enzyme made by HRV called 3Cpro activated NLRP1 in human airway cells.

They saw that the 3Cpro enzyme cut into NLRP1 at a specific point, triggering a form of inflammatory 'cell death', which is an important process in rapidly clearing pathogens like HRV during an infection.

http://news.ntu.edu.sg/pages/newsdetail.aspx?URL=http://news.ntu.edu.sg/news/Pages/NR2020_Oct141201-1079.aspx&Guid=53a7d43f-42d2-49df-a2f5-d56ef9fe68ed&Category=News+Releases

https://science.sciencemag.org/content/early/2020/10/21/science.aay2002