宿主细胞DEAD-box RNA解旋酶DDX1对猪传染性胃肠炎病毒感染的抑制作用及机制研究

批准号:
31972692
项目类别:
面上项目
资助金额:
57.0 万元
负责人:
谢立兰
依托单位:
学科分类:
兽医免疫学
结题年份:
2023
批准年份:
2019
项目状态:
已结题
项目参与者:
谢立兰
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中文摘要
DDX1是宿主细胞中广泛存在的蛋白,可与多种病毒的核酸或蛋白质结合,甚至帮助病毒抵抗天然免疫,以促进病毒复制。猪传染性胃肠炎病毒(TGEV)是引起仔猪腹泻的主要病原,给世界养猪业造成严重的经济损失。我们的前期研究表明,沉默DDX1后TGEV诱导的β干扰素启动子活性显著降低,病毒增殖上调,超表达的作用则相反,提示DDX1在TGEV感染中发挥了重要的抑制作用。本项目拟构建过表达和敲低DDX1基因的细胞系,采用流式细胞术、激光共聚焦显微镜及荧光定量PCR、蛋白免疫印迹等技术,从吸附、侵入、生物合成和释放各个环节评价DDX1在TGEV感染中的作用;鉴定蛋白关键功能域;分析RLR通路和TLR通路及其相关信号分子在DDX1调控病毒增殖中的作用,从而揭示DDX1负调控TGEV增殖的具体环节及其可能的分子机制。该基础研究将为DDX1负调控其他病毒感染奠定基础,为进一步预防和控制猪传染性胃肠炎提供理论依据。
英文摘要
The human DEAD-box RNA helicase1 (DDX1) in the DEAD-box family is expressed ubiquitously in host cells. Previous studies have demonstrated that DDX1 can bind nucleic acids or proteins of many viruses and help the viruses evading the immunologic surveillance of the host cells. DDX1 plays a important enhancement role in several virus replication. Transmissible Gastroenteritis Virus (TGEV) is the major pathogen causing diarrhea in piglets, which caused economy loss in swine production worldwide.Our preliminary data showed that silencing the DDX1 via RNAi facilitates TGEV propagation with the reduction of the IFN-β promoter activity, while over-expression of DDX1 inhibit TGEV replication. In this study, TGEV will be used as a virus infection model to explore the inhibition mechanisms of DDX1. Cells in which DDX1 gene is over expressed or knocked down will be constructed. Flow cytometry, laser confocal microscopy techniques, real-time PCR and western-blot assay will be used to evaluate the the role of DDX1 in the adsorption, penetration, protein synthesis and release step of TGEV infection. The functional domain of the DDX1 protein reponsible for TGEV propagation will be further identified by mutagenesis experiments, and the role of RLR pathway and TLR pathway and its related signaling molecules in the regulation of TGEV proliferation by DDX1 will be investigated.This study would add more clues to elucidate the biological function of DDX1 and the pathogenesis of TGEV.which will also provide us with useful information to better design vaccines against TGEV infection.
期刊论文列表
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科研奖励列表
会议论文列表
专利列表
DOI:10.1016/j.vaccine.2022.08.054
发表时间:2022-09-22
期刊:VACCINE
影响因子:5.5
作者:Cao, Xiaoling;Zai, Junjie;Zhao, Qingzhen;Xie, Lilan;Li, Yaoming
通讯作者:Li, Yaoming
DOI:--
发表时间:2021
期刊:重庆医学
影响因子:--
作者:罗祥;黄雯琪;谢立兰
通讯作者:谢立兰
DOI:10.1016/j.virol.2021.02.010
发表时间:2021-06
期刊:Virology
影响因子:3.7
作者:Xie L;Yi K;Li Y
通讯作者:Li Y
DOI:10.1016
发表时间:2018
期刊:J Infect
影响因子:--
作者:Nannan Pang;Fengbo Zhang;Shaoyu Li;Yuejie Zhu;Chuntao Zhang;Mengting An;Hongying Wang;Wulamu Mamuti;Jianbing Ding;Haining Fan
通讯作者:Haining Fan
DOI:DOI: 10.1089/mab.2023.0010
发表时间:2023
期刊:MONOCLONAL ANTIBODIES IN IMMUNODIAGNOSIS AND IMMUNOTHERAPY
影响因子:--
作者:Lilan Xie;Fang Lin;Peiling Dong;Yaoming Li
通讯作者:Yaoming Li
DDX1在猪传染性胃肠炎病毒非结构蛋白nsp14激活NF-κB信号通路中的作用机制
- 批准号:31402181
- 项目类别:青年科学基金项目
- 资助金额:25.0万元
- 批准年份:2014
- 负责人:谢立兰
- 依托单位:
国内基金
海外基金
