核 hnRNPA2B1 启动并放大对DNA病毒的先天免疫反应
Lei Wang1,2, Mingyue Wen2, Xuetao Cao3,2,4
1National Key Laboratory of Medicinal Chemical Biology, College of Life Science, Nankai University, Tianjin 300071, China.
Science (New York, N.Y.)
|July 20, 2019
概括
异质核核蛋白A2B1 (hnRNPA2B1) 感知核中的病毒DNA,从而启动抗病毒干扰素的产生. 这种蛋白质还增强了细胞质抗病毒信号通路,对宿主防御至关重要.
科学领域:
- 免疫学
- 分子生物学
- 病毒学
背景情况:
- 核病原体衍生的DNA传感仍然是先天免疫的一个关键问题.
- 了解病毒DNA如何触发宿主防御机制对于开发抗病毒策略至关重要.
研究的目的:
- 阐明异质核核核蛋白A2B1 (hnRNPA2B1) 在感知核病毒DNA中的作用.
- 研究hnRNPA2B1引发和放大对DNA病毒的先天免疫反应的分子机制.
主要方法:
- 免疫光显微镜用于追踪 hnRNPA2B1 的定位.
- 生物化学试验用于研究hNRNPA2B1二元化和脱甲基化.
- 评估mRNA修饰和蛋白质相互作用的RNA免疫沉和西部涂抹.
- 干扰素报告测试以测量抗病毒反应
主要成果:
- 核 hnRNPA2B1 识别病毒 DNA 并通过 JMJD6 进行脱甲基化.
- 脱甲基的hnRNPA2B1转移到细胞质中,激活了TANK结合激酶1-干扰素调节因子3 (TBK1- IRF3) 途径.
- 促进cGAS,IFI16和STINGmRNA的m6A修饰和传输,从而放大细胞质抗病毒信号.
结论:
- hnRNPA2B1是核病毒DNA的关键传感器,可以启动干扰素-α/β (IFN-α/β) 的产生.
- hnRNPA2B1通过增强STING依赖的细胞质抗病毒信号通路来增强先天免疫力.
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