I型干扰素在机体抗病毒固有免疫应答中发挥关键作用，而病毒可通过调控I型干扰素的产生及其应答过程完成免疫逃逸。我们初步实验发现，与正常人群相比，感染RSV病毒的病人外周血Dbf2p-相关激酶NDR1表达明显下调，RNA病毒(RSV和VSV)或DNA病毒(HSV-1和MHV68)感染显著下调巨噬细胞中NDR1的表达。而NDR1表达降低或者缺失显著抑制进VSV感染的的I型干扰素、炎症细胞因子及干扰素诱导蛋白ISGs的生成，促进VSV病毒的复制，提示病毒感染可能通过下调NDR1的表达产生免疫逃逸。本项目拟在此基础上利用NDR1基因敲除小鼠，免疫共沉淀及质谱分析等技术，明确NDR1对抗病毒天然免疫反应的调控作用及分子机制，丰富NDR1分子的生理、病理功能。同时探讨病毒诱导 NDR1表达下调的分子机制，可为阐明病毒逃逸免疫系统的监控提供新的理论基础，并为感染性疾病防治提供新靶点。

Type I Interferon plays key role in anti-viral innate immune response. To counteract the cellular defense and secure viral replication, viruses have evolved effective strategies to evade immune surveillance pathways including impairing IFN induction or blocking signaling downstream of the IFNα/β receptor. To our interesting, NDR1 mRNA is significantly reduced in peripheral blood samples from patients infected with respiratory syncytial virus (RSV) comparing to those from the healthy control. The downregulated mRNA and protein levels of NDR1 were further observed in mouse peritoneal macrophages (PMs) infected with RNA virus including RSV and vesicular stomatitis virus (VSV) and DNA viruses including herpes simplex virus 1(HSV-1) and murine herpesvirus 68 (MHV68). Moreover, our data showed that NDR1 knockdown or knockdown inhibits the virus infection induced- proinflammatory cytokines, type I interferon and antiviral ISGs production and promotes the viral infection and replication in macrophage. These preliminary results not only indicate the importance of NDR1 in antiviral innate immunity, but also indicate that NDR1 may be regulated by virus infections and involved in immune response escaping. We will further clarify the role of NDR1 in the anti-viral immune response and the related molecular mechanisms. Also, we will explore the underlined mechanisms by which virus infection inhibits the expression of NDR1. All these data will reveal a novel immune evasion pathway exploited by viruses and provide novel targets for the therapy of infection disease.