Acute respiratory virus infections predispose the cystic fibrosis (CF) lung to chronic bacterial colonization, which contributes to high mortality. For reasons unknown, respiratory virus infections have a prolonged duration in CF. Here, we demonstrate that mice carrying the most frequent cystic fibrosis transmembrane conductance regulator (CFTR) mutation in humans, ΔF508, show increased morbidity and mortality following infection with a common human enterovirus. ΔF508 mice demonstrated impaired viral clearance, a slower type I interferon response and delayed production of virus-neutralizing antibodies. While the ΔF508 mice had a normal immune cell repertoire, unchanged serum immunoglobulin concentrations and an intact immune response to a T-cell-independent antigen, their response to a T-cell-dependent antigen was significantly delayed. Our studies reveal a novel function for CFTR in antiviral immunity and demonstrate that the ΔF508 mutation in cftr is coupled to an impaired adaptive immune response. This important insight could open up new approaches for patient care and treatment.

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Keywords antibody response, antiviral defense, Coxsackievirus, cystic fibrosis, immunity
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Journal The Journal of Infectious Diseases
Svedin, E. (Emma), Utorova, R. (Renata), Hühn, M.H. (Michael H.), Larsson, P.G. (Pär G), Stone, V.M. (Virginia M.), Garimella, M. (Manasa), … Flodström-Tullberg, M. (2017). A Link Between a Common Mutation in CFTR and Impaired Innate and Adaptive Viral Defense. The Journal of Infectious Diseases, 216(10), 1308–1317. doi:10.1093/infdis/jix474