甲型流感病毒引起的急性呼吸道传染病，会造成广泛流行，严重危害公众健康。甲流病毒激活模式识别受体信号，诱导下游干扰素调节蛋白（IRF）3和IRF7活化，启动I型干扰素（IFN-I）表达。IFN-I是抗病毒免疫的关键因子，但其确切调控机制仍有待阐明。我们前期研究显示：N-Myc和STAT交互蛋白（Nmi）可作用于巨噬细胞Toll样受体（TLR）4，激活核因子（NF）-КB，调控炎症因子表达。本课题利用Nmi敲除小鼠（Nmi-/-），进一步探索Nmi在甲流病毒性肺炎发病中的作用。在体外实验中，我们将敲除或过表达Nmi，明确Nmi是否直接作用于IRF7或者通过招募E3泛素连接酶，介导IRF7的降解，从而负向调控IFN-I通路。该研究将揭示Nmi在甲流病毒感染免疫调控中的关键作用及分子机制，为甲流病毒性肺炎防治提供新的策略和靶标。

Acute respiratory infections caused by influenza A virus can be widespread epidemics and seriously endanger public health. The virus activates pattern recognition receptors, induces the activation of downstream transcription factor IRF3 and IRF7, and initiates the expression of type I interferon (IFN-I). IFN-I is a key factor in antiviral host immunity, but its exact regulatory mechanisms need to be illuminated. Our previous study had demonstrated that N-Myc and STAT interactor (Nmi) can activate the Toll-like receptor 4 of macrophages and induce the expression of inflammatory cytokines through the activation of NF-КB . In the present study, we investigate role of Nmi in the pathogenesis of influenza A virus pneumonia, using Nmi knockout mice (Nmi-/-). We further explore whether Nmi directly targets IRF7 or recruits E3 ubiquitin ligase to induce degradation of IRF7, thus negatively regulating the IFN-I pathway. Our study will reveal the key role and molecular mechanisms of Nmi in regulating IFN-I signaling, and then provide a novel target for the prevention and treatment for influenza A virus pneumonia.