Cell Rep . H1N1 Influenza Virus Cross-Activates Gli1 to Disrupt the Intercellular Junctions of Alveolar Epithelial Cells

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Cell Rep


. 2020 Jun 30;31(13):107801.
doi: 10.1016/j.celrep.2020.107801.
H1N1 Influenza Virus Cross-Activates Gli1 to Disrupt the Intercellular Junctions of Alveolar Epithelial Cells


Tao Ruan ¹ , Jing Sun ² , Wei Liu ² , Richard A Prinz ³ , Daxin Peng ⁴ , Xiufan Liu ⁴ , Xiulong Xu ⁵



Affiliations

• PMID: 32610119
• DOI: 10.1016/j.celrep.2020.107801

Abstract

Influenza A virus (IAV) primarily infects the airway and alveolar epithelial cells and disrupts the intercellular junctions, leading to increased paracellular permeability. Although this pathological change plays a critical role in lung tissue injury and secondary infection, the molecular mechanism of IAV-induced damage to the alveolar barrier remains obscure. Here, we report that Gli1, a transcription factor in the sonic hedgehog (Shh) signaling pathway, is cross-activated by the MAP and PI3 kinase pathways in H1N1 virus (PR8)-infected A549 cells and in the lungs of H1N1 virus-infected mice. Gli1 activation induces Snail expression, which downregulates the expression of intercellular junction proteins, including E-cadherin, ZO-1, and Occludin, and increases paracellular permeability. Inhibition of the Shh pathway restores the levels of Snail and intercellular junction proteins in H1N1-infected cells. Our study suggests that Gli1 activation plays an important role in disrupting the intercellular junctions and in promoting the pathogenesis of H1N1 virus infections.

Keywords: E-cadherin; Gli1; MAP kinase; Occludin; PI3 kinase; Snail; ZO-1; epithelial junctions; influenza A virus.