REGULATION OF RIG-I MEDIATED ANTIVIRAL INNATE IMMUNITY

RIG-I 介导的抗病毒先天免疫的调节

• 批准号: 8357994
• 负责人: Michaela Ulrike Gack
• 金额: $ 16.64万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-05-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8357994
• 关键词: Affect; Antiviral Agents; Early Diagnosis; Funding; Genes; Goals; Grant; Hepatitis C virus; Immune system; Integration Host Factors; Interferon Type I; Interferons; Invaded; Mediating; Molecular; National Center for Research Resources; Natural Immunity; New England; Outcome; Play; Post-Translational Protein Processing; Primates; Principal Investigator; Production; Proteins; RNA Virus Infections; RNA Viruses; Regulation; Research; Research Infrastructure; Resources; Role; Signal Pathway; Signal Transduction; Source; Tretinoin; United States National Institutes of Health; Viral; Viral Pathogenesis; Virus; Virus Diseases; base; cost; cytosolic receptor; human TRIM25 protein; influenzavirus; knowledge of results; receptor; response; sensor; ubiquitin-protein ligase; viral RNA

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.

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子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，其感测病毒的保守结构组分并随后启动导致I型干扰素（IFN）诱导的信号级联。视黄酸诱导基因I（RIG-I）是一种重要的细胞质受体，可感应RNA病毒，包括流感病毒和丙型肝炎病毒。本研究的主要目的是研究宿主先天免疫系统如何识别病毒感染并触发IFN应答，特别关注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-1和RING泛素E3连接酶TRIM 25在IFN对RNA病毒感染的应答中起关键作用。尽管最近发现RIG-I/TRIM 25信号通路中的分子组分产生了丰富的知识，但其抗病毒活性的调节尚未得到很好的研究;但正是IFN产生的调节决定了病毒感染和发病机制的结果。因此，本研究致力于鉴定RIG-I翻译后修饰，并研究翻译后修饰如何影响RIG-I活性以限制病毒复制。此外，本研究的目的是确定在RIG-I信号通路的调节中具有关键作用的宿主因子，以及阐明它们在RIG-I宿主对RNA病毒感染的监测中的作用。