RIG-I- AND TRIM25-MEDIATED IMMUNE RESPONSE AND EVASION OF INFLUENZA A VIRUS

RIG-I 和 TRIM25 介导的免疫反应和甲型流感病毒的逃避

• 批准号: 8357995
• 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/8357995
• 关键词: Antiviral Agents; Antiviral Response; Avian Influenza; Biological; Family member; Funding; Goals; Grant; Human; Immune response; Influenza A virus; Interferons; Mediating; National Center for Research Resources; Natural Immunity; New England; PTPN11 gene; Primates; Principal Investigator; Protein Family; Proteins; RNA Viruses; Regulatory Pathway; Research; Research Infrastructure; Resources; Role; Signal Transduction; Source; TRIM Gene; Ubiquitination; United States National Institutes of Health; Virus; Virus Diseases; Work; base; cost; human TRIM25 protein; influenzavirus; novel; receptor; response; swine influenza; 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 interconnection between the cytosolic viral RNA receptor RIG-I and the TRIM protein family member, TRIM25, represents a novel regulatory pathway that is important for the induction of interferon (IFN)-mediated host innate immunity against various RNA viruses, including influenza A viruses. To antagonize the host antiviral IFN response, viruses have evolved numerous sophisticated mechanisms. Our previous work demonstrated that the NS1 protein of human, avian and swine influenza A viruses interacts with and inhibits TRIM25 ubiquitin E3 ligase, thereby potently suppressing RIG-I ubiquitination and signal transducing activity. Thus, our goal here is to delineate the detailed mechanisms by which influenza A virus NS1 inhibits the RIG-I- and TRIM25-triggered IFN response. In addition, this study attempts to unveil the biological role of TRIM25 in the host antiviral response against influenza virus infection.

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。 细胞内病毒RNA受体RIG-I与TRIM蛋白家族成员TRIM25之间的相互连接代表了一种新的调控途径，对于诱导干扰素(干扰素)介导的宿主对包括甲型流感病毒在内的各种RNA病毒的天然免疫具有重要意义。为了对抗宿主的抗病毒干扰素反应，病毒进化出了许多复杂的机制。我们以前的工作证明，人、禽流感和猪流感病毒的NS1蛋白与TRIM25泛素E3连接酶相互作用并抑制TRIM25泛素E3连接酶，从而有效地抑制RIG-I泛素化和信号传导活性。因此，我们的目标是描述甲型流感病毒NS1抑制RIG-I和TRIM25触发的干扰素反应的详细机制。此外，本研究试图揭示TRIM25在宿主对流感病毒感染的抗病毒反应中的生物学作用。