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Antiviral defenses are diminished at birth in cystic fibrosis pig airways
Journal article   Peer reviewed

Antiviral defenses are diminished at birth in cystic fibrosis pig airways

Jennifer A. Bartlett, Miguel E. Ortiz, Linda S. Powers, Christine L. Wohlford-Lenane, Camilla E. Hippee, Laura Marquez Loza, Justin W. Kaufman, Brajesh K. Singh, Daniel I. Sands, Eric D. Huntemann, …
Journal of cystic fibrosis
08/01/2026
DOI: 10.1016/j.jcf.2026.07.1985
PMID: 42542415

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Abstract

•The CF pig model allows us to study the antiviral responses of CF lungs in very early life, prior to the onset of inflammation and lung disease.•Airway epithelia from newborn CF and non-CF pigs respond similarly to influenza infection.•However, newborn CF pigs show greater viral loads and immune responses than non-CF pigs when challenged with influenza in vivo.•Impairment of antiviral responses is present at birth in CF pigs. There 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. We 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. We 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. Our 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.
Cystic Fibrosis Antiviral CF pig Host defense Virus

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