中文版 | English
题名

戊型肝炎病毒调控细胞周期相关线粒体动态变化促进病毒复制机制研究

其他题名
Hepatitis E virus regulates cell cycle-related mitochondrial dynamic to promote viral replication
姓名
姓名拼音
LIU Xiaoman
学号
12133131
学位类型
硕士
学位专业
0710 生物学
学科门类/专业学位类别
07 理学
导师
袁静
导师单位
深圳市第三人民医院
论文答辩日期
2024-05-09
论文提交日期
2024-07-05
学位授予单位
南方科技大学
学位授予地点
深圳
摘要

戊型肝炎病毒(hepatitis E virusHEV)感染是急性肝炎的最常见原因,近年来被发现在器官移植病人、需要化疗的恶性血液肿瘤患者和艾滋病病毒感染者中引起慢性感染。一些病毒被报道通过调节宿主细胞的细胞周期和/或线粒体动态促进自身复制,但缺乏 HEV 相关报道。因此,本文探究 HEV 是否可以通过调控宿主细胞周期相关线粒体动态变化促进病毒复制。

通过建立 HEV 感染 Huh7.5 细胞模型,发现 HEV 感染可以显著提高线粒体融合蛋白 OPA1 MFN1 表达水平,诱导线粒体融合;在 OPA1 MFN1 敲除 Huh7.5 细胞中,由 HEV 引发的线粒体融合被消除,HEV 感染引起的 自噬被显著 抑制, 部分干扰素 刺激基 因(Interferon-stimulated genes ISG)转录以 HEV 依赖或独立的形式被激活,HEV 复制水平下降,这提示 HEV 调控 线 粒体 化促 自身 利用 式细 术和 Western blotting HEV 使 宿 G0/G1 期,并显著降低 G0/G1 期调控蛋白 CDK4 表达水平;通过羟基脲使细胞 G0/G1 期比例升高,发现 G0/G1 期同步化组细胞线粒体融合,感染HEV 后发现病毒复制水平明显增强,这提示 HEV 可以通过调控细胞周期相关线粒体动态来促进自身复制。在 HEV 结构蛋白 ORF2 质粒转染细胞模型中,羟基脲处理显著提高了 ORF2 的表达量,这进一步验证了细胞周期与HEV 复制的相关性。综上,HEV 可以通过调控宿主细胞停滞在 G0/G1 期并激发线粒体融合从而促进自身病毒复制,该机制为探究 HEV 持续感染提供新的思路。

其他摘要

 

关键词
语种
中文
培养类别
独立培养
入学年份
2021
学位授予年份
2024-07
参考文献列表

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刘小曼. 戊型肝炎病毒调控细胞周期相关线粒体动态变化促进病毒复制机制研究[D]. 深圳. 南方科技大学,2024.
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