RIG-I 样受体识别胞质中病毒RNA，激活机体抗病毒先天免疫应答。过早或失调的先天免疫应答对宿主有害，RIG-I介导的病毒免疫应答必须受到精细的调控。虽然对调控RIG-I介导的抗病毒免疫应答已有一些了解，但我们对于RIG-I介导的抗病毒免疫还不是相当了解。.我们发现E3连接酶NEDD4通过其相关联的N4BP3与RIG-I相互作用，负调控RIG-I介导的抗病毒免疫应答。研究还发现，NEDD4和N4BP3的表达加强RIG-I的泛素化修饰，特异性地降解仙台病毒诱导的RIG-I蛋白。.本项目拟对E3连接酶蛋白NEDD4负调控RIG-I介导的抗病毒免疫应答机理做深入研究,首次发现NEDD4通过对RIG-I的泛素化修饰，促进RIG-I的降解，负调控RIG-I介导的抗病毒信号通路。研究结果将使我们对机体精密调控RIG-I介导的先天免疫应答有新的认识。

Innate immunity plays the first line of defense against human and animal resistance to viral infections. RIG-I-like receptors (RLRs) recognize viral RNA in the cytoplasm and activate antiviral signaling pathways, resulting in the.production of type I interferons (IFN) and other pro-inflammatory cytokines. A premature or dysregulated innate immune response can be adverse to the host, the RIG-I-mediated antiviral immune response must be tightly regulated. It is known that multiple E3 ligase proteins play a vital role in regulating RIG-I-mediated antiviral innate immune signaling pathway, but we are not quite aware of RIG-I-mediated antiviral immunity. .In screening for the regulatory protein of RIG-I, we found that the E3 ligase NEDD4 interacts with RIG-I via its own associated N4BP3, negatively regulating the RIG-I-mediated antiviral immune response. Further studies revealed that the expression of NEDD4 and N4BP3 enhanced the ubiquitination of RIG-I and specifically degraded the RIG-I protein induced by Sendai virus. .This project intends to conduct an in-depth study on the mechanism of negative regulation of RIG-I-mediated antiviral immune response by E3 ligase protein NEDD4. It was first discovered that NEDD4 promotes the degradation of RIG-I and negatively regulates the RIG-I-mediated antiviral signaling pathway through ubiquitination of RIG-I. Therefore, the results of the study gave a new illuminating of the precise regulation of RIG-I-mediated innate immune response.