Biophysical Society Thematic Meeting | Ascona 2026

Mechanobiology of Infection

Monday Speaker Abstracts

AIRWAY EPITHELIA CLEAR RHINOVIRUS BY EXTRUDING INFECTED CELLS AT THE COST OF VIRAL DISSEMINATION Faith Fore 1,2 ; Dustin C Bagley 1,2 ; Rocio T Martinez-Nunez 3 ; Julia Aniscenko 4 ; Sebastian Johnston 4 ; Jody Rosenblatt 1,2 ; 1 King's College London, Randall Centre for Cell and Molecular Biophysics, London, United Kingdom 2 The Francis Crick Institute, London, United Kingdom 3 King's College London, Infectious Diseases, London, United Kingdom 4 Imperial College London, National Heart and Lung Institute, London, United Kingdom Rhinoviruses (RV), the primary cause of the common cold and a major trigger of asthma exacerbations and related hospitalisations, predominantly infect airway epithelia. These tissues maintain barrier integrity by removing damaged or excess cells through cell extrusion, a conserved homeostatic mechanism. While extrusion can eliminate infected cells, some pathogens exploit this process to facilitate dissemination. Here, we show that RV-infected cells are selectively extruded from airway epithelia, reducing viral burden to ~4% within 24 hours. We term this process virus-induced cell extrusion (VICE), a barrier-dependent mechanism observed in both 16HBE14o ⁻ bronchial monolayers and fully differentiated primary human airway epithelia. In contrast, BEAS-2B cells, which fail to form tight monolayers, cannot eliminate infected cells and instead accumulate viral burden, underscoring the importance of epithelial architecture in antiviral defence. VICE proceeds in two distinct waves. An early, non-apoptotic phase is driven by stretch-activated channels (SACs), as demonstrated by sensitivity to SAC inhibitors (Gd³ ⁺ , GsMtx4), and occurs prior to complete viral internalisation, independent of dynamin-mediated endocytosis. A later apoptotic phase depends on viral replication. Both phases require sphingosine-1-phosphate (S1P) signalling through the S1P2 receptor, identifying S1P as a central regulator of extrusion during infection. Despite promoting viral clearance, extrusion expels viable, virus-laden cells that remain infectious and can initiate infection in naïve epithelia. Thus, VICE acts as a cell-intrinsic, leukocyte-independent mechanism that rapidly removes infected cells while increasing the potential for viral dissemination to new hosts. Together, these findings redefine airway epithelia as active drivers of antiviral defence and reveal a fundamental trade-off between pathogen clearance and transmission.

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