King's College London

The study, led by scientists at King’s College London and the Francis Crick Institute, shows that airway cells respond to rhinovirus infection by physically pushing infected cells out of the tissue in a process the researchers have named virus-induced cell extrusion (VICE). This response can remove most infected cells from the airway lining within 24 hours. However, the expelled cells remain alive and infectious, potentially allowing the virus to reach new cells.

The researchers found that VICE happens in two distinct waves. The first begins rapidly, before the virus has fully entered the cell, while a second wave occurs later after the virus has replicated itself inside the cell and caused the cell to die.

This reveals two different ways in which the airway lining can respond to infection: an early response to the incoming virus and a later response to cells in which the virus has replicated.

Rhinoviruses are the leading cause of the common cold and usually cause mild illness, but they can cause more serious respiratory disease in young children, older people, people with weakened immune systems and those with chronic lung conditions such as asthma and COPD.

The airway lining is the body's first physical barrier against inhaled viruses and other threats. While it is known to detect infections and coordinate responses involving the immune system, this study shows that airways cells can also take direct action by physically removing infected cells.

The team studied rhinovirus infection in human airway cells grown in the laboratory. They found that when the cells were able to work together as a healthy layer, they could remove infected cells and limit infection within the tissue. When this process was disrupted, more virus built up in the airway cells.

The study was carried out using human airway cell models, including airway cells designed to reproduce important features of the human airway lining. The researchers also observed VICE in mouse lung tissue.

The findings provide new insight into the role of the airway lining in defending against respiratory viruses. The researchers say that the direct removal of infected cells by epithelial tissue has been overlooked in studies of viral infection, which have traditionally focused on the role of immune cells.

Further research is needed to understand whether the same mechanism operates against other respiratory viruses and how viruses might exploit or evade it.

Lead author Dr Faith Fore, based at the Faculty of Life Sciences & Medicine at King's College London and the Francis Crick Institute, said:

“We typically think of the cells lining our airways as a simple physical barrier, leaving the heavy lifting of clearing infections to the immune system. What we found is that the epithelium itself actively fights back by physically throwing out infected cells.

“The airway gets rid of the infected cell, but it doesn't destroy the virus. Because the expelled cells can still infect new cells, it creates a double-edged defence. Extrusion helps the tissue clear the immediate infection, but the expelled cells remain a potential source of viral spread.”

Senior and corresponding author Professor Jody Rosenblatt, who leads a seconded laboratory at the Francis Crick Institute, added:

“This study expands our understanding of how cells lining our airways protect themselves, showing that a process that helps maintain healthy tissue can also act as a built-in defence against viruses.

“It suggests that cells lining our tissues possess evolutionarily ancient mechanisms for protecting themselves. Understanding these fundamental tissue defence mechanisms could change how we think about the earliest stages of viral infection.”