Rhinovirus C15 infection induces airway epithelial cell remodeling and robust inflammatory responses: Potential implications for airway obstruction in children. Yiran Li

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Mucosal Immunol. 2025 Sep 18:S1933-0219(25)00092-3. doi: 10.1016/j.mucimm.2025.09.002. Online ahead of print.

ABSTRACT

Despite recognition of rhinovirus-C (RV-C) as a cause of severe respiratory exacerbations, little is known about the pathogenesis of RV-C infections. We infected mucociliary-differentiated primary tracheobronchial epithelial cells with RV-C15 or RV-A16. Initial RNASeq data showed that, compared to RV-A16, RV-C15 decreased expression of genes related to ciliary function while increasing expression of genes associated with mucus secretion and inflammation. Using different airway epithelial cell isolates, we confirmed greater reduction in DNAI2 and FOXJ1 (regulates production of motile cilia) and increased FOXA3 (regulates mucin -related gene expression) after RV-C15 infection compared to RV-A16. Similarly, nasal swab samples from children with RV-C but not RV-A infections showed significantly decreased DNAI2 and FOXJ1 mRNA compared to controls. While both RV-C15 and RV-A16 infection of airway epithelial cells increased mRNA expression and secretion of MUC5AC, RV-C15 induced greater airway surface liquid thickness, as measured by FITC-dextran staining. DAPT, a Notch inhibitor, reversed the effects of RV-C15 on DNAI2, FOXJ1 and FOXA3 expression. RV-C15 induced loss of α-acetyl tubulin, extrusion of airway epithelial cells, dissociation of ZO-1 from tight junctions, reduced ciliary beat frequency and decreased epithelial cell transepithelial electrical resistance. Finally, protein abundance of pro-inflammatory cytokines in cell supernatants and nasal samples also tended to be higher after RV-C infection. We conclude that RV-C causes significant disruptions in airway epithelial cell ciliary function which may lead to airway obstruction. Such disruptions may play a role in the severity of RV-C respiratory tract infections.

PMID:40975321 | DOI:10.1016/j.mucimm.2025.09.002

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