REGULATION OF RIG-I MEDIATED ANTIVIRAL INNATE IMMUNITY

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 宿主对入侵病毒的早期检测依赖于有限数量的细胞内受体，这些受体感知病毒的保守结构成分，随后启动信号级联反应，从而诱导I型干扰素(IFN)的诱导。维甲酸诱导基因I(RIG-I)是检测包括流感病毒和丙型肝炎病毒在内的RNA病毒的重要受体。这项研究的主要目的是研究宿主先天性免疫系统如何识别病毒感染并触发干扰素反应，特别是RIG-I蛋白及其活性的调节。我们以前的研究表明，病毒RNA传感器RIG-I和环泛素E3连接酶TRIM25在干扰素抗RNA病毒感染的反应中发挥关键作用。尽管最近发现的RIG-I/TRIM25信号通路的分子组成产生了丰富的知识，但对其抗病毒活性的调节还没有得到很好的研究，但正是对干扰素产生的调节决定了病毒感染和致病的结果。因此，本研究致力于确定RIG-I的翻译后修饰，并研究翻译后修饰如何影响RIG-I的活性以限制病毒复制。此外，本研究旨在识别在RIG-I信号通路调控中起关键作用的宿主因子，并阐明它们在RIG-I宿主抗RNA病毒感染监测中的作用。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The early detection of invading viruses by the host depends on a limited number of intracellular receptors that sense conserved structural components of viruses and subsequently initiate signaling cascades leading to type-I-interferon (IFN) induction. Retinoic acid-inducible gene I (RIG-I) has emerged as a key cytosolic receptor for sensing RNA viruses, including influenza virus and hepatitis C virus. The main goal of this study is to investigate how the host innate immune system recognizes virus infection and triggers IFN responses, with a specific focus on the RIG-I protein and the regulation of its activity. Our previous studies demonstrated that the viral RNA sensor RIG-I and the RING ubiquitin E3 ligase TRIM25 play key roles in the IFN response against RNA virus infection. Despite the wealth of knowledge resulting from recent discoveries of molecular components in the RIG-I/TRIM25 signaling pathway, the regulation of their antiviral activities has not been well studied; but it is exactly the regulation of the IFN production, which dictates the outcome of the viral infection and pathogenesis. Thus, this study is dedicated to identify RIG-I posttranslational modifications, and to investigate how posttranslational modifications affect the RIG-I activity to limit viral replication. Furthermore, this study aims at identifying host factors with a pivotal role in the regulation of RIG-I signaling pathway, as well as elucidating their roles for RIG-I host surveillance against RNA virus infections.