A critical role of NLRP6 in West Nile virus pathogenesis in mice

NLRP6 在小鼠西尼罗河病毒发病机制中的关键作用

• 批准号: 8635669
• 负责人: PENGHUA WANG
• 金额: $ 20.81万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-04-10 至 2015-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8635669
• 关键词: Address; Affect; Alzheimer' s Disease; Antiviral Agents; Astrocytes; Atherosclerosis; Bacteria; Bacterial Infections; Binding; Biochemical; Biological Assay; Biology; Brain; Caspase-1; Cells; Co-Immunoprecipitations; Colitis; Colon; Complex; Coupled; Data; Dendritic Cells; Development; Disease; Enzyme-Linked Immunosorbent Assay; Epithelial; Epithelial Cell Proliferation; Epithelial Cells; Family; Flavivirus; Gastrointestinal tract structure; Homeostasis; Human; Immune; Immune response; In Vitro; Inflammation; Inflammatory; Interferons; Interleukin-1; Mass Spectrum Analysis; Measures; Meningoencephalitis; Messenger RNA; Molecular; Molecular Genetics; Multiple Sclerosis; Mus; Myofibroblast; NF-kappa B; Natural regeneration; Neuraxis; Neurons; Non-Insulin-Dependent Diabetes Mellitus; Nucleotides; Parasites; Pattern; Peritoneal Macrophages; Physiological; Play; Production; Proteins; RNA Viruses; Reporting; Risk Factors; Role; Sendai virus; Serum; Siblings; Signal Transduction; Stimulus; Sting Injury; Testing; Time; Viral Encephalitis; Virus; Virus Diseases; Virus Replication; West Nile virus; cell type; cytokine; fight against; fungus; in vivo; insight; knockout gene; macrophage; member; microbiome; monocyte; neurotropic; neutrophil; overexpression; pathogen; prevent; public health relevance; receptor; repaired; response; therapeutic vaccine; tumorigenesis; vaccine development; viral RNA; virus pathogenesis

West Nile virus (WNV) is the most significant cause of viral encephalitis in the USA, responsible for over 1400 lethal human meningoencephalitis cases since 1999. Addressing the fundamental questions regarding host-WNV interactions is an integrated and indispensable part of the effort towards development of vaccines and therapeutics. This project will investigate the critical role of NLRP6, a poorly characterized member of the NOD (nucleotide- binding oligomerization domain) like receptor (NLR) family, in controlling WNV pathogenesis in mice. NLRP6 has been recently demonstrated to play a protective role in development of chemically induced colitis as well as colitis-induced tumorigenesis, and to maintain the gut microbiome homeostasis by preventing inflammation-inducing bacteria from colonizing the colon. More recently, NLRP6 was shown to negatively regulate NF-kB signaling during bacterial infection. However, our results show that NLRP6 helps mammalian hosts fight against WNV infection and reduce WNV lethality by enhancing type I IFN response. This project will continue investigating the physiological functions of NLRP6 in WNV infection in vivo, and elucidate the underlying mechanisms through biochemical, molecular and genetic approaches.

西尼罗河病毒（WNV）是美国病毒性脑炎的最重要原因， 自1999年以来，超过1400例致命的人类脑膜脑炎病例。解决 关于宿主-西尼罗河病毒相互作用的基本问题是一个不可或缺的组成部分， 疫苗和治疗方法的发展。该项目将调查 NLRP 6的关键作用，NLRP 6是NOD的一个特征不佳的成员（核苷酸结合蛋白）。 寡聚化结构域）样受体（NLR）家族在控制小鼠中的WNV发病机制中的作用。 NLRP 6最近已被证明在化学性肿瘤的发展中起保护作用。 诱导的结肠炎以及结肠炎诱导的肿瘤发生，并维持肠道微生物组 通过防止炎症诱导细菌在结肠定植来维持体内平衡。更 最近，NLRP 6显示在细菌感染期间负调节NF-κ B信号传导。 然而，我们的研究结果表明，NLRP 6有助于哺乳动物宿主对抗WNV感染， 通过增强I型IFN应答降低WNV致死率。本项目将继续调查 NLRP 6在体内WNV感染中的生理功能，并阐明其潜在的作用机制。 通过生物化学、分子和遗传学方法研究其机制。