抗凋亡分子c-FLIP在寨卡病毒感染中的作用及机制研究
结题报告
批准号:
32000116
项目类别:
青年科学基金项目
资助金额:
24.0 万元
负责人:
罗欢乐
依托单位:
学科分类:
病毒学
结题年份:
2023
批准年份:
2020
项目状态:
已结题
项目参与者:
罗欢乐
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中文摘要
孕妇妊娠期感染寨卡病毒可导致胎儿流产、小头症等先天性异常。已有研究报道寨卡病毒诱导的过度细胞凋亡及炎症反应是其主要的致病机理,然而宿主调控这两个进程引发胎儿先天性发育缺陷的重要分子和相关机制尚不明确。c-FLIP作为重要的抗凋亡因子,不仅与细胞凋亡、坏死性凋亡相关,还参与调节宿主的炎症信号通路。我们发现寨卡病毒感染胎盘细胞增强c-FLIP的基因转录水平,且c-FLIP的上游调控分子Peli1促进寨卡病毒引发的胎儿宫内生长受限,因此推测c-FLIP很可能参与寨卡病毒感染。我们拟在细胞模型上首先确定Peli1是否通过c-FLIP影响寨卡病毒感染,并揭示c-FLIP对寨卡病毒感染的影响和相关机制,最后利用基因缺陷小鼠分析c-FLIP对寨卡病毒感染及其导致的胎儿先天性异常的作用机制。总之我们将阐明c-FLIP在寨卡病毒感染中的作用及相关机制,为寻找治疗寨卡病毒感染的新靶点提供理论依据。
英文摘要
Zika virus (ZIKV) infection during pregnancy can cause birth defects including microcephaly and abortion. Dysregulated apoptosis and inflammation induced by ZIKV have been reported being the main factors of ZIKV pathogenicity, however, it is still unclear how the host regulate these two processes to lead to disease. As an anti-apoptotic protein, c-FLIP is not only regulating apoptosis and necroptosis, but also involved in important signaling pathways related to inflammation. Our previous study demonstrated the mRNA level of c-FLIP in ZIKV infected placenta cells was upregulated, and Peli1-the upstream molecular of c-FLIP can enhance intrauterine growth restriction. Thus we speculate that c-FLIP is possibly involved in ZIKV infection. For our current study, we will first elucidate if Peli1 regulate ZIKV infection through c-FLIP and explore the mechanism of c-FLIP affecting ZIKV infection utilizing different cells lines. We will also uncover the mechanism for ZIKV causing birth defects in c-FLIP deficient mouse model. Overall, we will reveal the role and mechanism of c-FLIP during ZIKV infection, providing new targets for treating ZIKV infection.
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DOI:10.1016/j.virusres.2023.199166
发表时间:2023-09
期刊:VIRUS RESEARCH
影响因子:5
作者:Chen, Qiqi;Li, Nina;Zeng, Shike;Wu, Shu;Luo, Xin;Zhang, Shengze;Zhu, Lin;Wu, Jiani;Xie, Ting;Bai, Shaohui;Zhang, Hao;Jiang, Zhiyuan;Lin, Shaoli;Wu, Nan;Jiang, Ying;Fang, Shisong;Wang, Xin;Shu, Yuelong;Luo, Huanle
通讯作者:Luo, Huanle
宿主因子DISC1在寨卡病毒感染导致胎儿先天性异常中的作用机制研究
  • 批准号:
    --
  • 项目类别:
    面上项目
  • 资助金额:
    54万元
  • 批准年份:
    2022
  • 负责人:
    罗欢乐
  • 依托单位:
国内基金
海外基金