Mice heterozygous for the F508del mutation in the cystic fibrosis transmembrane conductance regulator anion channel display attenuated cardiopulmonary dysfunction and lung injury after influenza H1N1 infection (406.4)

Influenza A viruses cause a highly-contagious respiratory disease associated with significant morbidity and mortality. The purpose of this study was to utilize F508del CFTR-heterozygous mice to determine the contribution of CFTR-mediated Cl- secretion to influenza pathogenesis and to evaluate CFTR as a therapeutic target. F508del CFTR-heterozygous progeny (HETs) and wild-type (WT) littermate controls were infected intranasally with 50 μl virus diluent (mock) or with 10,000 FFU/mouse influenza A/WSN/33 (H1N1) for 1-6 days. Body weight, lung mechanics, cardiopulmonary function and levels of pulmonary inflammatory mediators were determined over the time of disease. Relative to WT littermate controls, infection-induced hypoxemia and bradycardia were attenuated in HETs at 2-6 days post-infection (d.p.i.), although weight loss and viral replication did not differ. At 2 and 6 d.p.i., alterations in lung function in infected WT mice were absent in HETs at both 2 and 6 d.p.i. Bronchoalveolar lavage fluid from infl...