Fig. 5.

Influenza virus alteration of cystic fibrosis transmembrane conductance regulator (CFTR) and epithelial sodium channel (ENaC) activity through the release of ATP/UTP. After influenza infection, both ATP and UTP were significantly increased 1 and 2 days postinfection due to viral infection of the lung epithelium. UTP is hydrolyzed to UDP and acts on the P2Y₆R receptor, leading to decreased amiloride-sensitive ion transport. Simultaneously, ATP is hydrolyzed to adenosine, which acts on the A₁-AR. Activation of the A₁-AR increases Cl⁻ secretion through CFTR. The combination of decreased Na⁺ absorption and increased Cl⁻ secretion leads to increased airway surface fluid and pulmonary edema. This is based on conclusions previously published (109). NKCC, Na⁺/K⁺/2Cl⁻; KC, K⁺ channels.