Randomized trial finds activation of α7 nAChR increases influenza A virus replication in lung cells, suggesting new treatment targets.
Key Points
This research aims to investigate how α7 nicotinic acetylcholine receptor (α7 nAChR) activation influences influenza A virus (IAV) replication in lung epithelial cells through a specific signaling pathway.
Human alveolar type II epithelial cells (A549) were used to evaluate the effects of the α7 nAChR agonist GTS-21 on IAV replication.
Viral replication was measured by quantifying PR8 M gene copies via qPCR and protein levels through western blot analysis.
Stable knockdown and overexpression of CAMK2B and NEDD4 were performed to assess their roles in GTS-21-mediated IAV replication.
Activation of α7 nAChR significantly promoted IAV replication while downregulating IFITM3 expression.
CAMK2B overexpression enhanced IFITM3 levels and supported the IFNβ/STAT1 signaling axis, while its knockdown suppressed IFITM3 and facilitated viral replication.
Knockdown of NEDD4 reduced viral titers and negated the pro-viral effect of GTS-21.