Interferon response genes in nasal epithelium to RV16 challenge in asthma patients links to viral clearance and common cold scores

We showed rhinovirus-16 (RV16) induces enhanced interferon response in bronchial epithelium from mild asthma patients 6 days post-infection, which correlates with eosinophilic inflammation and lung function (PMID:30296526). The aim is to determine if nasal epithelial cells (NECs) showed similar responses to RV16 over time and if it relates to viral clearance. Moderate asthma patients (n=20), on inhaled corticosteroids (ICS), were challenged with RV16 (GMP by U-BIOPRED). RNA sequencing was performed in nasal brushings obtained at day 3, 6 and 14 post-infection and 7 days prior. Also, in blood at day 6 after RV16 and 4 days before. The top differentially expressed gene sets were interferon alpha and gamma response genes, which were upregulated (>2.5-fold) after RV16 at day 3 and 6, returning to near-baseline at day 14. Asthma patients clearing virus at day 6 are early resolvers, at day 14 were categorized as late resolvers and those that did not clear virus at day 14, were the unresolved group. Asthma patients clearing virus early and late had enhanced interferon response genes at days 3 and 6, while the unresolved group had no enhanced interferon response genes compared to baseline. The daily common cold scores peaked at days 3 to 5 and correlated positively with the interferon response genes at day 3 (R=0.58), but not with the other timepoints. Interferon response genes were also enhanced at day 6 after RV16 in blood. NECs from most moderate asthma patients despite the use of ICS, had an early interferon response to RV16 challenge, which is required for viral clearance. This interferon response relates to worsened upper respiratory tract symptoms.