Regulation of influenza virus replication by Wnt/β-catenin signaling

Sunil More, Xiaoyun Yang, Zhengyu Zhu, Gayan Bamunuarachchi, Yujie Guo, Chaoqun Huang, Keith Bailey, Jordan P. Metcalf, Lin Liu

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Article numbere0191010
JournalPloS one
Volume13
Issue number1
DOIs
StatePublished - Jan 2018
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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