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型肝炎病毒改变过氧体的形态和功能
Esther Martin de Fourchambault1, Nathalie Callens1, Jean-Michel Saliou2
1Université de Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U 1019 - UMR9017 - CIIL - Center for Infection and Immunity of Lille, Lille, France.
Frontiers in microbiology
|October 9, 2023
概括
型肝炎病毒 (HCV) 改变受感染细胞中的过氧体功能和形态. 尽管如此,去除过氧体并不会影响HCV复制,这表明它对细胞氧化还原平衡有特定的影响.
科学领域:
- 肝病学 肝病学是一种肝病学.
- 细胞生物学 细胞生物学
- 病毒学 病毒学
背景情况:
- 慢性型肝炎病毒 (HCV) 感染会破坏细胞代谢,特别是脂质代谢和氧化还原平衡,导致肝脏疾病的发病.
- 目前尚不完全了解HCV诱导病原体的确切机制.
研究的目的:
- 研究过氧体在HCV感染和发病过程中的作用.
- 确定HCV如何影响过氧体的功能和形态.
主要方法:
- 利用基于APEX2的近距离生物化来识别HCV复制复合体附近的蛋白质.
- 使用共聚焦显微镜观察HCV感染的Huh-7细胞中的过氧体转移和形态变化.
- 使用CRISPR/Cas9生成过氧体缺乏的Huh-7细胞,以评估对HCV复制的过氧体必要性.
- 分析了HCV感染细胞和亚基因组复制品中的活性氧物种 (ROS) 水平和催化酶活性.
主要成果:
- 在HCV复制复合体附近确定了ACBD5,一种超氧体膜蛋白.
- 在大约30%的HCV感染细胞中观察到过氧体转移和改变形态.
- 证明过氧体缺失没有影响HCV复制动力学或传染性标位.
- 发现ROS增加和触酶活性降低,特别是在HCV复制细胞的过氧体内,表明过氧体氧化还原平衡受损.
结论:
- 在HCV感染期间,过氧体的功能和形态发生变化.
- 肝炎病毒特别影响过氧体的氧化还原平衡,而不是影响细胞质或线粒体的ROS.
- 过氧体对HCV复制没有必要,但它们的功能和结构变化是感染的结果.
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