miR-214在乌鳢水泡病毒感染SSN-1细胞中的调控机制研究

批准号:
31602195
项目类别:
青年科学基金项目
资助金额:
20.0 万元
负责人:
涂加钢
依托单位:
学科分类:
C1908.水产生物病原学与病害控制
结题年份:
2019
批准年份:
2016
项目状态:
已结题
项目参与者:
赵联忠、刘晓丹、孙琳丹、张驰、伊丽竹
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中文摘要
乌鳢水泡病毒(SHVV)感染导致我国乌鳢养殖业重大经济损失,目前还没有有效的防治措施。MicroRNA是一类非编码的小分子RNA,在病毒感染过程中发挥重要的调控作用。我们前期研究发现SHVV感染乌鳢细胞(SSN-1)导致细胞的microRNA-214 (miR-214)下调表达,而过表达miR-214类似物抑制SHVV的增殖。进一步从SHVV基因组搜索miR-214的靶基因发现N和P基因是miR-214的潜在靶基因。因此,本项目拟对miR-214在SHVV感染SSN-1细胞中的调控机制进行研究。主要内容包括:(1)在SHVV感染SSN-1细胞过程中,哪些病毒成分导致miR-214下调表达;(2)miR-214是否与潜在靶基因N和P的mRNA结合,降低N、P基因mRNA的含量,从而抑制SHVV的增殖。研究结果对认识miR-214如何调控SHVV的感染和研发新型抗SHVV的药物具有重要的意义。
英文摘要
Snakehead vesiculovirus (SHVV) infection has caused great economic loss to snakehead fish culture in China, and there are not any efficient preventive and therapeutic ways. MicroRNA is a class of small non-coding RNA that plays an important role in the regulation of virus infection. Snakehead vesiculovirus (SHVV) infection has caused great economic loss to snakehead fish culture in China, and there are not any efficient preventive and therapeutic ways. MicroRNA is a class of small non-coding RNA that plays an important role in the regulation of virus infection. Our previous research indicates that cellular microRNA-214 (miR-214) was down regulated in striped snakehead fish (SSN-1) cells upon SHVV infection, and overexpression of miR-214 mimic inhibited the replication of SHVV. Further target-gene prediction of miR-214 in SHVV genome revealed that N and P genes were the potential target genes of miR-214. Therefore, this project aims at illuminating the regulatory role of miR-214 in SSN-1 cells upon SHVV infection. The main studies included: (1) Identify viral components that are involved in the down regulation of miR-214 in SSN-1 cells during the infection of SHVV; (2) Investigate whether miR-214 decreases the concentration of mRNAs of N and P genes via binding to these mRNAs, thus resulting in the inhibition of SHVV replication. The obtained results are highly important to reveal how miR-214 regulates SHVV infection and develop novel drugs against SHVV infection.
乌鳢水泡病毒(SHVV)是从患病杂交鳢分离的一株弹状病毒,其感染对我国乌鳢养殖业造成了巨大经济损失。但是,我们对SHVV的致病机理知之甚少。.本项目围绕microRNA miR-214在SHVV感染条纹月鳢(SSN-1)细胞中的调控机制展开研究,取得了以下研究成果:1)SHVV感染SSN-1细胞导致细胞内miR-214下调表达,且呈现时间、剂量的依赖性;2)转染miR-214类似物可抑制SHVV增殖,而转染miR-214抑制剂可促进SHVV增殖,说明miR-214是SHVV增殖的负调控因子;3)靶基因预测及双荧光报告系统验证表明SHVV的N和P基因是miR-214的靶基因,过表达miR-214能抑制N和P基因的表达;4)通过转录组测序及双荧光报告系统验证发现AMP依赖的蛋白激酶(AMPK)是miR-214的靶基因,siRNA敲降AMPK可抑制SHVV的增殖,同时上调表达IFN-α。而siAMPK对SHVV增殖的抑制可以通过添加miR-214抑制剂得到一定程度的回补,表明miR-214可通过靶向AMPK抑制SHVV增殖;5)进一步研究发现糖原合成酶(GS)也是miR-214的靶基因,过表达miR-214降低细胞内GS基因的表达,siGS敲降细胞内GS基因的表达显著抑制SHVV增殖,这种抑制作用能通过添加miR-214抑制剂回补,表明miR-214也能通过靶向宿主的GS基因抑制SHVV增殖。.本项目的研究结果为揭示SHVV如何利用宿主miRNA调节自身增殖的分子机制奠定基础,也为药物靶点的发掘提供理论依据。
期刊论文列表
专著列表
科研奖励列表
会议论文列表
专利列表
MiR-214 inhibits snakehead vesiculovirus (SHVV) replication by targeting host GS
MiR-214 通过靶向宿主 GS 抑制蛇头水泡病毒 (SHVV) 复制
DOI:10.1016/j.fsi.2018.10.028
发表时间:2019
期刊:Fish & Shellfish Immunology
影响因子:4.7
作者:Zhang Chi;Li Ningqiu;Fu Xiaozhe;Lin Qiang;Lin Li;Tu Jiagang
通讯作者:Tu Jiagang
Development of a reverse genetics system for snakehead vesiculovirus (SHVV)
蛇头水泡病毒(SHVV)反向遗传学系统的开发
DOI:10.1016/j.virol.2018.10.002
发表时间:2019-01-02
期刊:VIROLOGY
影响因子:3.7
作者:Feng, Shuangshuang;Su, Jianguo;Tu, Jiagang
通讯作者:Tu, Jiagang
MicroRNA miR-214 inhibits snakehead vesiculovirus replication by promoting IFN-a expression via targeting host adenosine 5’-monophosphate-activated protein
MicroRNA miR-214 通过靶向宿主腺苷 5α-单磷酸激活蛋白促进 IFN-a 表达来抑制蛇头水泡病毒复制
DOI:--
发表时间:2017
期刊:Frontiers in immunology
影响因子:7.3
作者:Chi Zhang;Shuangshuang Feng;Wenting Zhang;Nan Chen;Abeer M. Hegazy;Wenjie Chen;Xueqin Liu;Lijuan Zhao;Jun Li;Li Lin;Jiagang Tu
通讯作者:Jiagang Tu
MicroRNA miR-214 inhibits snakehead vesiculovirus replication by targeting the coding regions of viral N and P.
MicroRNA miR-214 通过靶向病毒 N 和 P 编码区抑制蛇头水泡病毒复制
DOI:10.1099/jgv.0.000854
发表时间:2017
期刊:Journal of General Virology
影响因子:3.8
作者:Zhang Chi;Yi Lizhu;Feng Shuangshuang;Liu Xueqin;Su Jianguo;Lin Li;Tu Jiagang
通讯作者:Tu Jiagang
DOI:--
发表时间:2019
期刊:水产学报
影响因子:--
作者:伊丽竹;徐镇;林蠡;涂加钢
通讯作者:涂加钢
聚合酶复合物L-P通过泛素化修饰调节乌鳢水泡病毒增殖和毒力的分子机制研究
- 批准号:--
- 项目类别:面上项目
- 资助金额:58万元
- 批准年份:2021
- 负责人:涂加钢
- 依托单位:
Leader RNA与N蛋白互作调节乌鳢水泡病毒增殖的分子机制研究
- 批准号:31972832
- 项目类别:面上项目
- 资助金额:58.0万元
- 批准年份:2019
- 负责人:涂加钢
- 依托单位:
国内基金
海外基金
