Abstract
Human rhinoviruses (HRV) are frequent cause of asthma exacerbations, however the influence of airway inflammation on the severity of viral infection is poorly understood. Here, we investigated how cytokine-induced remodeling of airway epithelium modulates antiviral response. We analyzed gene expression response in in vitro differentiated bronchial epithelium exposed to cytokines and next infected with HRV16. IL-13-induced mucous cell metaplasia (MCM) was associated with impaired ciliogenesis and induction of antiviral genes, resulting in lower susceptibility to HRV. Epithelial-mesenchymal transition caused by TGF-β was associated with increased virus replication and boosted innate response. Moreover, HRV infection per se caused transient upregulation of MCM markers and growth factors, followed by low-level virus replication and shedding. Our data suggest that the outcome of HRV infection depends on the type of lower airway inflammation and the extent of epithelial damage. Type-2 inflammation (eosinophilic asthma) may induce antiviral state of epithelium and decrease virus sensitivity, while growth factor exposure during epithelial repair may facilitate virus replication and inflammatory response. Additionally, responses to HRV were similar in cells obtained from asthma patients and control subjects, which implicates that antiviral mechanisms are not intrinsically impaired in asthma, but may develop in the presence of uncontrolled airway inflammation.