Influenza infection impairs both ENaC and CFTR function in primary mouse tracheal epithelial cells

Influenza infection causes edematous pathophysiological processes in upper airway. The airway surface fluid is finely tuned by apically located epithelial sodium channels (ENaC) and cystic fibrosis transmembrane conductance regulator (CFTR), in addition to Na/K-ATPase in the basolateral membrane in epithelia. To investigate the effects of influenza type A virus (H1N1 PR8 strain) on transepithelial fluid transport, we infected primary mouse tracheal epithelial cells isolated from C57/B6 mice and measured short-circuit currents (Isc) using an Ussing chamber system. Our results show that H1N1 viruses decrease basal amiloride-sensitive Isc levels markedly from 20.5 ± 2.7 to 4.5 ± 0.7 μA/cm2 (n=8, P<0.01). Similarly, ENaC-associated Isc fraction activated by forskolin, a cyclic AMP-elevating agent, is reduced from 14.1 ± 3.2 to 3.4 ± 0.6 μA/cm2 (n=6, P<0.01). On the other hand, forskolin-evoked CFTR activity (CFTRinh172-inhibitable Isc fraction) decreases significantly from 18.3 ± 2.6 to 7.8 ± 0.8 μA/cm2 (n=8,...