Rhinovirus-induced human lung tissue responses mimic respiratory disease signatures allowing evaluation of therapeutics

Human rhinovirus (RV) is a major risk factor for COPD and asthma exacerbations, but exploration of RV pathogenesis has been hampered by a lack of disease relevant model systems. We performed a detailed characterization of host mRNA responses to RV infection in human precision cut lung tissue ex vivo (comparing to previously published asthma and COPD studies) and explored the impact of antiviral treatment. Genomic analyses revealed that RV not only induced anti-viral immune responses but also triggered changes in epithelial cell-associated pathways. Strikingly, the RV response in PCLS was reflective of gene expression changes described previously in COPD and asthma patients. While RV-induced host immune responses were abrogated by rupintrivir, RV-triggered epithelial processes were largely refractory to antiviral treatment. Precision cut lung slices were prepared in duplicate from 5 human donors before challenging with rhinovirus 1B or control for 24 or 72 hours, with or without addition of 100nM pleconaril or rupintrivir to culture