MODULATION OF INNATE IMMUNE RESPONSES BY CYTOMEGALOVIRUS

巨细胞病毒对先天免疫反应的调节

• 批准号: 8357775
• 负责人: Klaus J Fruh
• 金额: $ 38.95万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 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/8357775
• 关键词: Cytomegalovirus; Funding; Genes; Grant; Human; Immune response; Immune system; Interferons; Macaca mulatta; Molecular; National Center for Research Resources; Primates; Principal Investigator; Proteins; Publishing; Research; Research Infrastructure; Resources; Source; Testing; United States National Institutes of Health; Viral; Virus; cost; gene induction; human IRF3 protein; interferon regulatory factor-3; research study; response

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 ultimate inability of the immune system to eliminate cytomegalovirus (CMV) from the host is likely due to sophisticated viral evasion mechanisms that target many aspects of the host immune system. In this project, we will try to gain a better understanding of the molecular mechanisms by which CMV modulates the induction of innate immune responses, particularly the interferon response. Specific Aim 1 is to identify how HCMV activates interferon-regulatory factor 3 (IRF3). This aim has been completed and the results have been published. Specific Aims 2 and 3 are to determine how human and rhesus CMV interfere with IRF3-dependent transcriptional induction of interferon-stimulated genes (ISGs). We have tested our original hypothesis that the tegument proteins pp65 and pp71 are responsible for inhibiting IRF3 activation by RhCMV by generating deletion viruses. However, since these viruses still inhibit IRF3 activation, we now hypothesize that RhCMV contains additional IRF3 inhibitory genes. Current experiments are aimed at identifying these genes. In addition, we now explore the inhibition of IFN-dependent ISG induction by RhCMV and we have generated evidence that HCMV also inhibits IRF3 activation.

该子项目是利用资源的众多研究子项目之一 由 NIH/NCRR 资助的中心拨款提供。子项目的主要支持 并且子项目的主要研究者可能是由其他来源提供的， 包括其他 NIH 来源。 子项目可能列出的总成本 代表子项目使用的中心基础设施的估计数量， NCRR 赠款不直接向子项目或子项目工作人员提供资金。 免疫系统最终无法从宿主中消除巨细胞病毒（CMV）可能是由于针对宿主免疫系统许多方面的复杂病毒逃避机制所致。在这个项目中，我们将尝试更好地了解 CMV 调节先天免疫反应（特别是干扰素反应）诱导的分子机制。具体目标 1 是确定 HCMV 如何激活干扰素调节因子 3 (IRF3)。该目标已完成，结果已公布。 具体目标 2 和 3 是确定人和恒河猴 CMV 如何干扰干扰素刺激基因 (ISG) 的 IRF3 依赖性转录诱导。 我们已经测试了我们最初的假设，即外皮蛋白 pp65 和 pp71 负责通过产生缺失病毒来抑制 RhCMV 激活 IRF3。然而，由于这些病毒仍然抑制 IRF3 激活，我们现在假设 RhCMV 含有额外的 IRF3 抑制基因。目前的实验旨在鉴定这些基因。此外，我们现在探索 RhCMV 对 IFN 依赖性 ISG 诱导的抑制，并且我们已经获得了 HCMV 也抑制 IRF3 激活的证据。