Late Breaking Abstract - Human airway epithelia clear rhinovirus-infected cells by extrusion

<fig><object-id>erj;64/suppl_68/PA5320/F1</object-id><object-id>F1</object-id><object-id>F1</object-id><graphic></graphic></fig> Rhinovirus (RV) infections cause most common colds and are a chief trigger of asthma exacerbations. Epithelial cells are the primary sites for RV infection. The epithelia remove compromised and supernumerary cells while preserving barrier function through cell extrusion. Here, we investigated how RV infection impacts extrusion. We show that the major and minor strains of RV induce extrusion of infected human epithelial cells, suggesting that ICAM-1 or LDLR are not the main drivers of viral-induced cell extrusion (VICE). VICE happens in two waves, the early and the later waves, respectively independent and dependent on apoptosis. Surprisingly, the epithelial viral burden is reduced to <5% within 24 hours of RV infection in 16HBE14o cells, indicating an important role of extrusion in innate immunity. Importantly, VICE requires an epithelial monolayer with intact junctions, as Beas2Bs, an epithelial cell line with serrated tight junctions and no adherens junctions, cannot extrude RV-infected cells, and instead accumulate RV over time. Epithelia that have eliminated the virus by extrusion become immune to subsequent RV infection. Extruded RV-infected cells act as viral bombs that can infect a new monolayer, however, when added to a post-extrusion monolayer, the viral bombs are phagocytosed. Our findings show the importance of cell extrusion in clearing Rhinovirus, thereby enabling a protective immunity without involving other immune system cells.