Rhinovirus Infection Results in Increased and More Persistent Dysregulation of Gene Expression

Rhinovirus is associated with 50-90% of asthma exacerbations in adults and children. We hypothesized that gene expression in asthmatics would be significantly dysregulated compared to non-asthmatics following Rhinovirus infection. Adults (20-33 years old), 5 with allergic asthma and 6 without (controls), were inoculated with Rhinovirus-16 and nasal epithelial samples were obtained 7 days prior to (T0), 2 days after (T1), and 7 days after inoculation (T2). RNA was extracted and used for RNA-seq analysis. Differential gene expression analysis was performed based on the negative-binomial statistical model of read counts as implemented in the edgeR Bioconductor package. At baseline, 57 genes were differentially expressed in asthmatics compared to controls (p adj < 0.05). In non-asthmatic controls, 62 genes were significantly altered from T0 to T1, including 27 genes whose expression changed at least 3-fold. Strikingly, in asthmatics, 1329 genes were significantly altered from T0 to T1, including 550 genes whose expression changed at least 3-fold. In controls, only 3 genes remained at least 3-fold dysregulated at T2, while in asthmatics, 50 genes still demonstrated at least a 3-fold change in expression even 7 days later. Healthy individuals with asthma have a substantially different response to Rhinovirus infection than non-asthmatic healthy controls. The quality of the response was significantly altered, and the magnitude of the response was increased in asthmatics. Further, the response persisted longer in asthmatics versus controls. Thus, in patients with asthma, the ability to sense Rhinovirus and the ensuing immune response is inherently altered.