登革病毒（DENV）病是世界上感染人数最多，威胁最严重的虫媒传染病之一，然而目前我们对于机体抗登革病毒免疫的机理十分不明确。近来研究表明，Notch介导了固有免疫细胞的多项功能。那么，Notch是否在固有免疫细胞抗登革病毒过程中发挥了作用呢？我们的预实验结果提示，DENV可通过I型干扰素诱导原代巨噬细胞中Notch分子高表达和通路激活；进一步的实验表明Notch通路激活对DENV复制具有抑制效应。由此，本项目将首先明确DENV 对Notch通路的调控作用，并阐明其调控的分子机制；并通过重组蛋白刺激、建立稳定细胞系、中和抗体实验、RNAi、过表达和抑制剂阻断等技术，从正反两方面来重点阐明Notch对于固有免疫和登革病毒复制的影响。本项目的实施将揭示DENV,Notch和固有免疫应答的相互关系，有助于阐明机体抗DENV感染的免疫机理，为登革病毒病防治药物开发提供新的作用靶点。

Dengue Virus (DENV) disease is one of the most prevalent and threatening arboviruscaused diseases worldwide. However, the mechanism of immune response against DENV remains unclear. Recent studies showed that Notch signaling pathway plays an important role in the innate immune cells. Our question is: Whether is the Notch signaling in macrophages and dendritic cells invovled in combating DENV infection? Our preliminary data demonstrated that in DENV-infected primary macrophages, expression of some Notch molecules was enhanced and Notch signaling was activated via type I Interferons. And the Notch activation in macrophages has an antiviral effect. Therefore, the first goal of current study is to validate the regulatory effects of DENV on the Notch signaling pathway, and to illustrate the underlying molecular mechanisms of DENV regulation on Notch signaling.Moreover, we will focus on the funcational analysis of Notch signaling on the innate immune response and DENV replication, by establishing stable cell clones expressing Notch ligands, antibody neutralzation assay, overexpression assay ,RNAi and inhibitor blockade assay ect. This study will illucidate the relationship between DENV, Notch and innate immunity, and shed light on the host immune response against DENV infection, providing potential targets for development of novel anti-DENV drugs.