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.

甲型流感病毒（IAV）主要感染气道和肺泡上皮细胞并破坏细胞间连接，导致细胞旁通透性增加。尽管这种病理变化在肺组织损伤和继发感染中起关键作用，但是IAV诱导的肺泡屏障损害的分子机制仍然不清楚。在这里，我们报告说，Gli1，在声波刺猬（Shh）信号传导途径中的转录因子，在H1N1病毒（PR8）感染的A549细胞和H1N1病毒感染的肺部中被MAP和PI3激酶途径交叉激活老鼠。Gli1激活诱导Snail表达，从而下调包括E-cadherin，ZO-1和Occludin在内的细胞间连接蛋白的表达，并增加细胞旁通透性。抑制Shh通路可恢复感染H1N1的细胞中Snail和细胞间连接蛋白的水平。我们的研究表明，Gli1激活在破坏细胞间连接和促进H1N1病毒感染的发病机理中起着重要作用。