The role of NLRP6 and DHX15 in control of infection by RNA viruses

NLRP6和DHX15在控制RNA病毒感染中的作用

• 批准号: 10321245
• 负责人: Erol Fikrig
• 金额: $ 41.88万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10321245
• 关键词: Antiviral Response; Coxsackie Viruses; Disease; Enteral; Epithelial Cells; Genetic Polymorphism; Hepatitis A; Host Defense; Human; Immune; Immune response; In Vitro; Infection; Infection Control; Inflammasome; Inflammatory Response; Innate Immune Response; Interferon Type I; Interferons; Intestines; Knock-in Mouse; Mediating; Microbe; Mitochondria; Molecular; Mus; Mutation; Nucleotides; Organoids; Pathway interactions; Pattern; Pattern recognition receptor; Physiological; Play; Proteins; RNA; RNA Helicase; RNA Virus Infections; RNA Viruses; Role; Rotavirus; Rotavirus Vaccines; Signal Pathway; Signal Transduction; Signaling Protein; System; Viral; Virus; Virus Diseases; antiviral immunity; cohort; enteric virus infection; helicase; in vivo; insight; intestinal epithelium; microorganism; pathogen; receptor; response; sensor; therapeutic target; vaccine failure

ABSTRACT Pattern recognition receptors sense pathogen-associated molecular patterns and mediate the earliest host innate immune response to infection. The cytosolic nucleotide oligomerization domain (NOD) like receptors (NLRs) are a highly conserved group of cytosolic proteins that play a central role in the immune response to diverse microorganisms, environmental insults and cellular danger signals. We have recently demonstrated a role for Nlrp6 in the control of enteric virus infection. Nlrp6 controls enteric virus infection in the intestine by interacting with a RNA sensor, Dhx15. Here we propose to define the mechanisms of NLRP6-mediated anti-viral pathways, to identify whether other helicases may also interact with NLRP6 (Aim 1), whether other relevant RNA viruses are recognized through this pathway, and whether mutations may underlie certain human cases of vaccine failures (Aim 2). A fuller understanding of the triggers and physiologic function and signaling pathways for NLRs will provide key insights to immune mechanisms involved in host defense and immune-mediated diseases.

摘要 模式识别受体感知病原体相关的分子模式并介导 宿主对感染最早的先天免疫反应。胞内核苷酸齐聚结构域 (NOD)样受体(NLR)是一组高度保守的胞浆蛋白，在 对各种微生物、环境侮辱和细胞危险信号的免疫反应。我们 最近证明了NLRP6在控制肠道病毒感染中的作用。NLRP6控制肠道 通过与RNA传感器Dhx15相互作用，肠道中的病毒感染。在这里，我们建议定义 NLRP6介导的抗病毒途径的机制，以确定其他解旋酶是否也可能 与NLRP6(AIM 1)相互作用，是否通过这一途径识别其他相关RNA病毒， 以及突变是否可能是某些人类疫苗失败病例的基础(目标2)。更饱满的人 了解NLRs的触发机制、生理功能和信号通路将提供关键 对宿主防御和免疫介导性疾病中涉及的免疫机制的见解。

项目成果

Nlrp9b inflammasome restricts rotavirus infection in intestinal epithelial cells.

NLRP9B炎性体限制了肠上皮细胞中的轮状病毒感染。

• DOI: 10.1038/nature22967
• 发表时间: 2017-06-29
• 期刊: Nature
• 影响因子: 64.8
• 作者: Zhu S;Ding S;Wang P;Wei Z;Pan W;Palm NW;Yang Y;Yu H;Li HB;Wang G;Lei X;de Zoete MR;Zhao J;Zheng Y;Chen H;Zhao Y;Jurado KA;Feng N;Shan L;Kluger Y;Lu J;Abraham C;Fikrig E;Greenberg HB;Flavell RA
• 通讯作者: Flavell RA

CXCL10 Signaling Contributes to the Pathogenesis of Arthritogenic Alphaviruses.

• DOI: 10.3390/v12111252
• 发表时间: 2020-11-02
• 期刊: Viruses
• 作者: Lin T;Geng T;Harrison AG;Yang D;Vella AT;Fikrig E;Wang P
• 通讯作者: Wang P

AgBR1 and NeSt1 antisera protect mice from Aedes aegypti-borne Zika infection.

• DOI: 10.1016/j.vaccine.2021.01.072
• 发表时间: 2021-03-19
• 期刊: Vaccine
• 影响因子: 5.5
• 作者: Marin-Lopez A;Wang Y;Jiang J;Ledizet M;Fikrig E
• 通讯作者: Fikrig E

Phase separation drives RNA virus-induced activation of the NLRP6 inflammasome.

相分离驱动 RNA 病毒诱导的 NLRP6 炎症小体激活

• DOI: 10.1016/j.cell.2021.09.032
• 发表时间: 2021-11-11
• 期刊: Cell
• 影响因子: 64.5
• 作者: Shen C;Li R;Negro R;Cheng J;Vora SM;Fu TM;Wang A;He K;Andreeva L;Gao P;Tian Z;Flavell RA;Zhu S;Wu H
• 通讯作者: Wu H

UBXN3B positively regulates STING-mediated antiviral immune responses.

• DOI: 10.1038/s41467-018-04759-8
• 发表时间: 2018-06-13
• 期刊: Nature communications
• 影响因子: 16.6
• 作者: Yang L;Wang L;Ketkar H;Ma J;Yang G;Cui S;Geng T;Mordue DG;Fujimoto T;Cheng G;You F;Lin R;Fikrig E;Wang P
• 通讯作者: Wang P