Division of Experimental Therapeutics, Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario, Canada; Institute of Medical Science, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
Virology. 2014 Jan 5;448:91-103. doi: 10.1016/j.virol.2013.09.022. Epub 2013 Oct 22.
Pandemic H1N1 influenza A (H1N1pdm) elicits stronger pulmonary inflammation than previously circulating seasonal H1N1 influenza A (sH1N1), yet mechanisms of inflammatory activation in respiratory epithelial cells during H1N1pdm infection are unclear. We investigated host responses to H1N1pdm/sH1N1 infection and virus entry mechanisms in primary human bronchial epithelial cells in vitro. H1N1pdm infection rapidly initiated a robust inflammatory gene signature (3 h post-infection) not elicited by sH1N1 infection. Protein secretion inhibition had no effect on gene induction. Infection with membrane fusion deficient H1N1pdm failed to induce robust inflammatory gene expression which was rescued with restoration of fusion ability, suggesting H1N1pdm directly triggered the inflammatory signature downstream of membrane fusion. Investigation of intra-virion components revealed H1N1pdm viral RNA (vRNA) triggered a stronger inflammatory phenotype than sH1N1 vRNA. Thus, our study is first to report H1N1pdm induces greater inflammatory gene expression than sH1N1 in vitro due to direct virus-epithelial cell interaction.
大流行性 H1N1 流感 A（H1N1pdm）引起的肺部炎症强于先前循环的季节性 H1N1 流感 A（sH1N1），但在 H1N1pdm 感染期间呼吸道上皮细胞中炎症激活的机制尚不清楚。我们研究了宿主对 H1N1pdm/sH1N1 感染的反应和病毒进入机制在体外原代人支气管上皮细胞中的作用。H1N1pdm 感染迅速引发了强烈的炎症基因特征（感染后 3 小时），而 sH1N1 感染则不会引发这种特征。蛋白分泌抑制对基因诱导没有影响。感染缺乏膜融合能力的 H1N1pdm 不能诱导强烈的炎症基因表达，而恢复融合能力则可以挽救这种情况，这表明 H1N1pdm 直接在膜融合下游触发了炎症特征。对病毒内成分的研究表明，H1N1pdm 病毒 RNA（vRNA）比 sH1N1 vRNA 引发更强的炎症表型。因此，我们的研究首次报道 H1N1pdm 在体外比 sH1N1 诱导更强的炎症基因表达，这是由于直接的病毒-上皮细胞相互作用。
