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.

该副本是利用资源的众多研究子项目之一 由NIH/NCRR资助的中心赠款提供。对该子弹的主要支持 而且，副投影的主要研究员可能是其他来源提供的 包括其他NIH来源。 列出的总费用可能 代表subproject使用的中心基础架构的估计量， NCRR赠款不直接向子弹或副本人员提供的直接资金。 免疫系统从宿主中消除巨细胞病毒（CMV）的最终无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调节先天免疫反应的诱导，尤其是干扰素反应的分子机制。具体目的1是确定HCMV如何激活干扰素调节因子3（IRF3）。这个目标已经完成，结果已经发布。 具体目的2和3是确定人类和恒河类CMV如何干扰IRF3依赖性转录诱导的干扰素刺激基因（ISGS）。 我们已经检验了我们的原始假设，即Tegument蛋白PP65和PP71负责通过产生缺失病毒来抑制RHCMV的IRF3激活。但是，由于这些病毒仍抑制IRF3激活，因此我们现在假设RHCMV包含额外的IRF3抑制基因。当前的实验旨在鉴定这些基因。此外，我们现在探讨了RHCMV对IFN依赖性ISG诱导的抑制作用，并且我们产生了HCMV也抑制IRF3激活的证据。