Antiviral defenses are diminished at birth in cystic fibrosis pig airways.

backgroundThere is evidence that antiviral defenses are impaired in airway epithelia derived from the lungs of people with cystic fibrosis (CF), however it is unclear whether this phenotype is an intrinsic feature of CF or an acquired trait that develops secondary to chronic airway infection and inflammation. To distinguish between these possibilities, we examined the antiviral responses of newborn CF pigs, prior to the onset of airway inflammation and chronic lung disease.

methodsWe performed an in vivo viral challenge experiment in newborn CF and non-CF pigs, using influenza A (IAV) as a model respiratory virus. To learn more about the contributions of epithelia in this setting, we carried out a parallel in vitro infection experiment using cultured airway epithelia derived from newborn CF and non-CF pig controls.

resultsWe found that viral growth kinetics and host antiviral responses were relatively similar in the cultured epithelia from CF and non-CF pigs. However, we observed divergent host responses in the animal experiment, with the newborn CF pigs exhibiting comparatively increased innate immune activation and increased viral loads after IAV challenge.

conclusionsOur findings indicate a reduced effectiveness of antiviral host defense at birth in the CF pig model and suggest that this phenotype is not driven solely by altered airway epithelial cell function. These results highlight a likely contribution of early life viral infections in initiating CF lung disease.