miRNA在补体介导甲型H1N1流感肺部炎症损伤中的作用及调控机制研究

Influenza is an acute respiratory disease caused by influenza A virus. The main nosogeny of influenza is that immunnity inflammation provoked by the infection leads to pathological injury, and complement pathway plays important role in the inflammation.Researches in recent year has found the miRNA also plays important role in the immunity inflammation response to the influenza A virus infection, but it is not clear whether the miRNAs play important modulating role in the inflammation through regulating the complement pathway during H1N1 influenza A virus infection.Before now, We have profiled cellular miRNA and mRNA of lung tissues from mice infected with H1N1 influenza A virus, analyzed miRNA-mRNA data with miRBase by bioinformatics methods and found complement molecules (C5、C2、C1R、C5aR1) are predicted targets of differently expressed miRNAs (miR-130b、miR-139-5p、miR-21、miR-30d、miR-574-3p).In this study, in order to know the miRNA effects on inflammation and clarify effect mechanism whether the differently expressed miRNAs regulate inflammation through modulating the complement pathway or not during H1N1 influenza virus A infection, we are to carry out a series of functional experiments on model of cell and mouse (including C5a、C2、C1R、C5AR1 knockout mouse)to further study it,such as reporter gene experiment, interfering miRNA expression experiments, complement (including activated complement) level detection experiments. The results will not only help to further elucidate the mechanism of influenza virus infection, also provide new ideas on treating the immunity damage induced by influenza A virus.

流感是严重威胁人类健康的急性传染病，免疫炎症反应是其主要致病机制，补体和miRNA均参与其调控，但尚不清楚miRNA如何通过调节补体来调控其免疫炎症反应。本研究前期通过检测甲型H1N1病毒感染小鼠后肺组织的miRNA和mRNA表达谱，获得差异表达的miR-130b、miR-139-5p、miR-21、miR-30d、miR-574-3p，利用生物信息学技术预测其靶基因为补体分子C5、C2、C1R和C5aR1。下一步拟通过报告基因鉴定以及普通小鼠和C5、C2、C1R、C5aR1缺陷小鼠感染模型阐明目标miRNA通过调节补体激活来调控流感病毒介导的肺部免疫损伤机制及其体内对病毒复制的影响，结合分子生物学、病理学和免疫学等方法研究miRNA调节补体通路及对流感炎症免疫反应的作用,以期进一步阐明流感病毒感染过程中的免疫损伤机制，为miRNA靶向干预治疗流感炎症免疫损伤提供新的思路和技术支持。

补体和miRNA均参与流感病毒感染的调控，但尚不清楚miRNA如何通过调节补体来调控其免疫炎症反应。本研究通过检测甲型H1N1病毒感染小鼠后肺组织的miRNA和mRNA表达谱，获得差异表达的miR-130b、miR-139-5p、miR-21、miR-30d、miR-574-3p，利用生物信息学技术预测其靶基因为补体分子C5、C2、C1R和C5aR1。通过报告基因鉴定以及普通小鼠和C5、C2、C1R、C5aR1缺陷小鼠感染模型，阐明了目标miRNA通过调节补体激活来调控流感病毒介导的肺部免疫损伤机制及其体内对病毒复制的影响，结合分子生物学、病理学和免疫学等方法研究miRNA调节补体通路及对流感炎症免疫反应的作用,初步阐明了流感病毒感染过程中的免疫损伤机制，为miRNA靶向干预治疗流感炎症免疫损伤提供新的思路和技术支持。