Interferon-Related Gene Expression in Respiratory Syncytial Virus (RSV) Infected Pediatric Bronchial Epithelial Cells (BECs) Is Inversely Correlated with Lung Function

Respiratory viral infection in early childhood, including that from RSV, has been previously associated with later development of obstructive lung disease. We sought to determine whether in vitro RSV infection of BECs from asthmatic children would induce specific gene expression patterns, and whether this would correlate with lung function measurements obtained from those same subjects. BECs from 26 asthmatic children with varying severity of obstructive lung disease were collected, cultured, and differentiated at an air liquid interface (ALI). Differentiated BECs were grown with RSV or virus free media for 96 hours and RNA was isolated for mRNA sequencing. Differential gene expression was assessed by linear modeling and correlation of differentially expressed genes and lung function measures were assessed by Pearson correlation with multiple testing correction. Findings were validated in an independent cohort of 9 asthmatics. RSV infection led to increased expression of ∼7000 genes in asthmatic BECs compared uninfected samples. 195 of these genes demonstrated increased expression in asthmatic subjects with fixed obstructive lung disease compared to asthmatic subjects without fixed obstruction and showed significant inverse correlation with FEV1 % predicted. These genes were highly enriched for interferon response genes. The findings were confirmed in an independent cohort. These results demonstrate that RSV infection of BECs from asthmatic children with fixed obstructive lung disease demonstrate a greater interferon response to infection than those with normal baseline lung function. This association suggests that an excessive antiviral response by bronchial epithelial cells could influence development of functional lung impairment.