A link between a common mutation in CFTR and impaired innate and adaptive viral defense

Abstract

Acute respiratory virus infections predispose the cystic fbrosis (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 fbrosis 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 signifcantly delayed. Our studies reveal a novel function for CFTR in antiviral immunity and demonstrate that the δF508 mutation in cfr is coupled to an impaired adaptive immune response. Tis important insight could open up new approaches for patient care and treatment.