USP18通过调节线粒体DNA释放来增强登革热病毒的复制
Jenn-Haung Lai1, De-Wei Wu2, Chien-Hsiang Wu2
1Department of Rheumatology, Allergy and Immunology, Department of Internal Medicine, Chang Gung Memorial Hospital, Lin-Kou, Tao-Yuan, Taiwan, ROC. laiandho@gmail.com.
Scientific reports
|November 18, 2023
概括
登革热病毒 (DENV) 通过USP18.18避开免疫系统. 这项研究揭示了USP18通过干扰素依赖和独立的线粒体通路调节DENV复制,影响病毒传播.
科学领域:
- 病毒学 病毒学
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
背景情况:
- 登革热病毒 (DENV) 构成了全球重大健康挑战.
- 乌比基特异性蛋白酶18 (USP18) 通过维持抗干扰素 (IFN) 效应,有助于DENV免疫逃避.
- 在调节DENV复制中USP18的精确机制尚未完全理解.
研究的目的:
- 研究USP18在DENV复制中的多方面的作用.
- 要确定USP18对DENV复制的调节是否超出了IFN的低响应性.
- 为了阐明参与USP18介导的DENV复制控制的特定线粒体路径.
主要方法:
- 使用的IFN信号阻断策略:IFN中和抗体,抗IFN受体抗体,Janus激酶抑制剂和IFNAR1淘汰细胞.
- 研究了在线粒体内的USP18定位.
- 分析了线粒体功能障碍的机制,包括ROS产生,膜电位变化,调动,OGG1表达,mtDNA氧化/碎片化和mPTP开放.
主要成果:
- USP18通过IFN相关和IFN无关路径影响DENV复制.
- 在线粒体中定位的USP18调节了线粒体DNA (mtDNA) 释放到细胞质中.
- 几种线粒体因素,包括mtROS,膜潜力,流量,OGG1,mtDNA完整性和mPTP,都与USP18控制的mtDNA释放有关.
结论:
- USP18在调节DENV复制中起着双重作用,影响IFN反应和线粒体完整性.
- 线粒体通路,特别是由USP18调节的mtDNA释放,对于控制DENV复制至关重要.
- 这项研究确定了USP18调节的关键线粒体组件,这些组件影响了DENV复制及其与IFN信号的相互作用.
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