Human airway epithelia clear rhinovirus-infected cells using two waves of cell extrusion

Rhinoviruses (RV) cause most common colds and asthma attacks. While RV typically infects airway epithelia, most studies infect cell lines that cannot form proper epithelial barriers. Cell extrusion is a highly conserved process that drives most epithelial cell death by seamlessly squeezing out excess live cells to maintain constant cell densities and a tight barrier. We discovered that healthy bronchial epithelia clear RV within 24 hours by selectively extruding infected cells, a process called virus-induced cell extrusion (VICE). In contrast, barrier-defective cells fail to clear the virus and accumulate infection. VICE occurs in two phases: an early wave triggered by mechanical signals, and a later wave dependent on viral replication. Although extrusion removes infection, virus-carrying expelled cells can still spread RV. These findings highlight extrusion’s dual role in both clearing and transmitting rhinovirus, independent of typical inflammation.