ORMDL3 是哮喘易感基因，与哮喘发病相关，哮喘和反复喘息患儿该基因表达增高，呼吸道合胞病毒 (RSV) 可诱发和加重哮喘和反复喘息，但机制不详。我们前期研究表明RNA病毒类似物poly (I:C) 可上调 ORMDL3 基因表达，该基因启动子区 IRF-3 位点在其中起重要作用，因此假设 poly (I:C) 和 RSV 可通过启动子区 IRF-3 位点调控 ORMDL3 的表达。本课题拟通过多种分子生物学实验技术和动物实验研究 RSV 对哮喘小鼠 IRF-3、ORMDL3 表达及气道炎症的影响；在细胞水平论证 poly (I:C) 和 RSV 对 ORMDL3 启动子、RNA和蛋白表达的调节作用及 IRF-3 在其中的介导作用。本研究将有助于阐明 RSV、IRF-3、ORMDL3 和哮喘之间的联系，为防治病毒诱发哮喘及研发哮喘药物新靶点提供理论和实验依据。

Orosomucoid 1-like protein 3 (ORMDL3) is a potential asthma candidate gene and is involved in the pathogenesis of asthma. The expression level of the ORMDL3 gene was upregulated in asthma and recurrent wheeze patients. Respiratory syncytial virus (RSV) infection was regarded as an important dangerous factor in the development and exacerbation of asthma and recurrent wheeze. But the molecular mechanisms involved in ORMDL3 regulation have not been fully elucidated. Our preliminary studies showed that poly (I:C) upregulated the expression levels of ORMDL3 gene. The transcription factor binding site of IRF-3 in the promoter region of ORMDL3 played an important role in the upregulation of ORMDL3 by poly (I:C). So we hypothesized that the regulatory effects of poly (I:C) and RSV infection to the expression of ORMDL3 were mediated by IRF-3. This study will research the relationship among the expression levels of IRF-3, ORMDL3 and airway inflammation in RSV-infected mouse asthma model in vivo. It will also demonstrate the regulatory effects of IRF-3, poly (I:C) and RSV infection to the promoter activities, the expression levels of RNA and protein of ORMDL3, and the binding of IRF-3 with the promoter by many experimental techniques of molecular biology. After using the method of knockdown of IRF-3 by siRNA, we will observe the changes of the promoter activities, the binding of IRF-3 with the promoter and the expression levels of ORMDL3 after the stimulation by poly (I:C) and RSV infection. This study may reveal a new mechanism among RSV, IRF-3, ORMDL3 and asthma and may provide experimental basis for the prevention of virus-inducted asthma and development of new targets for the therapy of asthma.