Airway epithelia clear rhinovirus infection via two waves of cell extrusion

Epithelial barriers represent the first line of defense against pathogens, yet their role in innate immunity is typically relegated to pathogen detection and immune cell recruitment. This perspective ignores a fundamental biological principle: Epithelia defended against pathogens long before complex immune systems evolved. Here, we demonstrate that human bronchial epithelium retains this ancestral capacity, autonomously clearing rhinovirus (RV) within 24 hours by selectively extruding infected cells, a process that we term virus-induced cell extrusion (VICE). VICE occurs in two waves: a rapid response occurring independently of complete virus entry, followed by a replication-dependent wave. Barrier-defective epithelia that cannot extrude do not eliminate RV. While VICE maintains barrier integrity and reduces local infection, it also expels virus-laden cells, which can infect fresh epithelia. Thus, VICE enables leukocyte-independent epithelial defense while inadvertently promoting viral spread, redefining epithelia as central to viral pathogenesis and host protection.