NONO检测核HIV体以促进cGAS介导的先天免疫激活
Xavier Lahaye1, Matteo Gentili1, Aymeric Silvin1
1Immunity and Cancer Department, Institut Curie, PSL Research University, INSERM U932, 75005 Paris, France.
Cell
|October 2, 2018
概括
蛋白NONO作为核中的HIV囊的关键传感器,对激活循环GMP- AMP合成酶 (cGAS) 免疫反应至关重要.
科学领域:
- 免疫学
- 病毒学
- 分子生物学
背景情况:
- 遗传免疫传感器检测病毒, 启动抗病毒免疫力.
- 循环GMP-AMP合成酶 (cGAS) 检测人类免疫细胞中的HIV DNA,但仅仅HIV DNA合成并不能保证免疫激活.
- 艾滋病毒囊蛋白在启动cGAS介导的免疫激活中发挥着关键作用.
研究的目的:
- 确定负责检测HIV囊的核传感器.
- 阐明HIV囊触发天生的免疫感应的机制.
- 了解细胞如何区分核病毒组件和自我.
主要方法:
- 核蛋白分离和共免疫沉测试以识别HIV囊相互作用蛋白.
- 在体外结合测试以确定NONO与HIV-1和HIV-2囊的结合亲和力.
- 编辑CRISPR/Cas9基因以减少人类细胞中的NONO.
- 在NONO枯竭细胞中评估HIV感染时的cGAS激活和局部化.
主要成果:
- 在核中,NONO蛋白直接与HIV结.
- 与HIV-1相比,NONO对HIV-2囊的结合亲和力更高.
- 在感染期间,NONO对于cGAS激活及其与HIVDNA的关联至关重要.
- NONO 识别了艾滋病毒囊中的一个保存区域,这表明逃脱突变的可能性有限.
结论:
- NONO作为HIV囊的一个关键核传感器.
- 这对启动抗病毒免疫力至关重要.
- 这种NONO介导的核病毒囊体检测代表了与生俱来的免疫策略,用于区分病毒病原体和宿主成分.
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