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: 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
• 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' 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

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年以来造成了1400多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开发疫苗和治疗方法的努力中不可或缺的一部分。该项目将研究NLRP 6在控制小鼠WNV发病机制中的关键作用，NLRP 6是NOD（核苷酸结合寡聚化结构域）样受体（NLR）家族的一个特征不明显的成员。NLRP 6最近已被证明在化学诱导的结肠炎以及结肠炎诱导的肿瘤发生的发展中起保护作用，并通过防止炎症诱导细菌在结肠中定殖来维持肠道微生物组稳态。最近，NLRP 6被证明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，并通过增强I型IFN应答降低WNV致死率。本项目将继续研究NLRP 6在体内感染西尼罗河病毒中的生理功能，并通过生物化学、分子和遗传学方法阐明其潜在机制。

项目成果

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.

• DOI: 10.1038/nmicrobiol.2017.20
• 发表时间: 2017-03-01
• 期刊: Nature microbiology
• 影响因子: 28.3
• 作者: Xiao X;Yang L;Pang X;Zhang R;Zhu Y;Wang P;Gao G;Cheng G
• 通讯作者: Cheng G