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

基本信息

批准号：
8835026
负责人：
PENGHUA WANG
金额：
$ 23万
依托单位：
NEW YORK MEDICAL COLLEGE
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-04-10 至 2016-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8835026
关键词：
Address Affect Alzheimer&apos 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 Health 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 genetic approach in vivo insight knockout gene macrophage member microbiome monocyte neurotropic neutrophil overexpression pathogen prevent receptor repaired response therapeutic vaccine tumorigenesis vaccine development viral RNA virus pathogenesis

项目摘要

DESCRIPTION (provided by applicant): 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.

描述（由申请人提供）：西尼罗河病毒 (WNV) 是美国病毒性脑炎的最重要原因，自 1999 年以来导致 1400 多例致命的人类脑膜脑炎病例。解决有关宿主与 WNV 相互作用的基本问题是一个综合且不可或缺的过程。开发疫苗和治疗方法的努力的一部分。该项目将研究 NLRP6 在控制小鼠 WNV 发病机制中的关键作用，NLRP6 是 NOD（核苷酸结合寡聚结构域）样受体 (NLR) 家族的一个尚未被充分表征的成员。最近已证明 NLRP6 在化学诱导的结肠炎的发展以及结肠炎诱导的肿瘤发生中发挥保护作用，并通过防止炎症诱导细菌在结肠定殖来维持肠道微生物组稳态。最近，NLRP6 显示在细菌感染期间负向调节 NF-kB 信号传导。然而，我们的结果表明，NLRP6 通过增强 I 型 IFN 反应，帮助哺乳动物宿主对抗 WNV 感染并降低 WNV 致死率。本项目将继续研究NLRP6在体内WNV感染中的生理功能，并通过生化、分子和遗传学方法阐明其潜在机制。

项目成果

期刊论文数量（3）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Blood meal acquisition enhances arbovirus replication in mosquitoes through activation of the GABAergic system.

DOI：
10.1038/s41467-017-01244-6
发表时间：
2017-11-02
期刊：
Nature communications
影响因子：
16.6
作者：
Zhu Y;Zhang R;Zhang B;Zhao T;Wang P;Liang G;Cheng G
通讯作者：
Cheng G

Flavivirus NS1 protein in infected host sera enhances viral acquisition by mosquitoes.

受感染宿主血清中的黄病毒 NS1 蛋白增强蚊子获取病毒的能力

DOI：
10.1038/nmicrobiol.2016.87
发表时间：
2016-06-20
期刊：
NATURE MICROBIOLOGY
影响因子：
28.3
作者：
Liu, Jianying;Liu, Yang;Nie, Kaixiao;Du, Senyan;Qiu, Jingjun;Pang, Xiaojing;Wang, Penghua;Cheng, Gong
通讯作者：
Cheng, Gong

A Mesh-Duox pathway regulates homeostasis in the insect gut.