Wnt/β-
catenin signaling is an essential pathway in cell cycle control. Dysregulation of the Wnt/β-
catenin signaling pathway during
viral infection has been reported. In this study, we examined the effect of modulating Wnt/β-
catenin signaling during influenza virus
infection. The activation of the Wnt/β-
catenin pathway by Wnt3a increased influenza virus
mRNA and virus production in in vitro in mouse lung epithelial E10 cells and
mRNA expresson of influenza virus genes in vivo in the lungs of mice infected with influenza virus A/Puerto Rico/8/34. However, the inhibition of Wnt/β-
catenin signaling by
iCRT14 reduced virus titer and viral gene expression in human lung epithelial A549 cells and viral replication in primary mouse alveolar epithelial cells infected with different influenza virus strains. Knockdown of β-
catenin also reduced
viral protein expression and virus production.
iCRT14 acts at the early stage of virus replication. Treatment with
iCRT14 inhibited the expression of the viral genes (vRNA,
cRNA and
mRNA) evaluated in this study. The intraperitoneal administration of
iCRT14 reduced viral load, improved clinical signs, and partially protected mice from influenza virus
infection.