The Role of Protein in Detecting the Common Cold Virus Revealed

In a recent study, a team of scientists at the Agency for Science, Technology and Research (A * STAR) at Nanyang Technological University, Singapore, discovered the role of proteins in detecting the common cold virus and initiating immune responses against infection.

In a recent study published in Science, they showed that the NLRP1 protein found in the skin and respiratory tract is a sensor for detecting human rhinovirus (HRV). When NLRP1 breaks through the respiratory tract, it triggers an immune response that causes inflammation of the lungs and causes symptoms of the common cold.

HRV is a major cause of common colds and acute respiratory diseases in children and adults, and in severe cases leads to bronchitis and pneumonia.

The team stated that discovering the purpose of NLRP1 may lead to new treatments for common cold symptoms, an infection that affects millions of people each year. They plan to work with clinicians to develop drugs that "turn off" or block NLRP1 to reduce the severity of HRV related disease symptoms. However, the team pointed out that blocking NLRP1 protein in human lung cells did not increase viral load.

"Now, we know that NLRP1 is the 'switch' of inflammation after the detection of the common cold virus, and the next step is to figure out how to prevent its activation and minimize the triggered inflammatory response," said assistant professor Fulin Zhong, author of the article.

Professor Zhong said their new insights into the function of the immune system could help scientists develop more effective therapies to treat other inflammatory diseases of the human respiratory tract.

“This work represents a major advance in our understanding of how the immune system uses specialized proteins to sense and defend against viral pathogens,” he said. “This knowledge will be useful in designing treatments for viral diseases including influenza and COVID-19.”

NLRP1 has been known to scientists for many years, but its exact purpose is unknown. It is a member of a family of proteins called “NLR” proteins that are sensors in the immune system that trigger the body's response to invading pathogens.

When the team began their study in 2017, they hypothesized that NLRP1 could act as a sensor for viruses because it is highly abundant in human skin and lungs, which are usually exposed to surfaces of viral pathogens.

The team screened NLRP1 against several viruses to see if it would trigger activation of the protein. After months of testing, they observed that an enzyme produced by HRV called 3Cpro activated NLRP1 in human respiratory cells.

They found that the 3Cpro enzyme cleaves NLRP1 at specific points, triggering some form of inflammatory “cell death”, an important process for rapid clearance of pathogens such as HRV during infection.