病原体驱动的CRISPR屏幕识别了TREX1作为在流感病毒感染期间DNA自我传感的调节者
Cason R King1, Yiping Liu2, Katherine A Amato1
1Department of Medical Microbiology & Immunology, University of Wisconsin-Madison, Madison, WI 53706, USA.
Cell host & microbe
|August 31, 2023
概括
这项研究揭示了流感病毒如何利用宿主TREX1通过降解线粒体DNA来复制,否则会触发抗病毒免疫力. 这突出了TREX1作为宿主-病原体相互作用的关键调节者.
科学领域:
- 病毒学 病毒学
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
背景情况:
- 宿主-病原体相互作用对于感染结果至关重要,但不完全理解.
- 现有的方法在探索宿主-病原体接口的全谱方面存在局限性.
研究的目的:
- 开发一种基于健康状况的新屏幕,以识别感染中后期阶段涉及的宿主因素.
- 为了发现流感病毒利用复制的宿主调节体.
主要方法:
- 工程流感病毒表达dCas9以调节宿主基因表达.
- 进行全基因组选,以确定亲病毒宿主因素.
- 研究了确定宿主因子TREX1在病毒复制和先天免疫反应中的作用.
主要成果:
- 确定了细胞质DNA外核酶TREX1作为一种亲病毒因素.
- 证明TREX1降解细胞质DNA,包括感染期间释放的线粒体DNA.
- 表明TREX1可以通过自身DNA阻止抗病毒信号通路 (cGAS-STING) 的激活,从而有助于流感病毒的复制.
结论:
- 流感病毒利用宿主TREX1抑制由自身DNA触发的先天免疫反应.
- 感染期间释放的线粒体DNA作为信号来放大先天免疫力,这是由TREX1.1调节的过程.
- 病原体驱动的基于健身的屏幕是发现感染宿主调节者的强大工具.
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