通过RIG-I介导的携带5'-二酸盐的RNA的识别获得抗病毒免疫力
Delphine Goubau1, Martin Schlee2, Safia Deddouche1
1Immunobiology Laboratory, Cancer Research UK, London Research Institute, 44 Lincoln's Inn Fields, London WC2A 3LY, UK.
Nature
|August 15, 2014
概括
RIG-I (可诱导酸的基因I) 识别了具有5'-二酸盐 (5'pp) 的病毒RNA,扩大了它在天生的免疫力中的作用. 这一发现增强了对细胞如何区分病毒入侵者和自我细胞的理解.
科学领域:
- 具有天生的免疫力.
- 分子病毒学分子病毒学
- 感应RNA 感应RNA 感应
背景情况:
- 哺乳动物细胞使用RIG-I类受体 (RLR),包括RIG-I和MDA5,来检测细胞质中的病毒RNA.
- RIG-I通常检测具有5'-三酸盐 (ppp) 末端和形末端,基配对区域的病毒RNA.
- 激活RIG-I启动信号级联,导致I型干扰素的产生,这对抗病毒防御至关重要.
研究的目的:
- 调查RIG-I是否可以调解5'-二酸盐 (5'pp) termini的病毒RNA的抗病毒反应.
- 为了确定RIG-I识别超出5'-pppRNA的最小RNA结构要求.
主要方法:
- 使用RIG-I和各种5'pp-RNA (来自reoviruses,酵母L-A病毒,体外转录和化学合成) 的结合分析.
- 功能性测试用于评估RIG-I依赖于5'pp-RNA的抗病毒反应.
- 在培养细胞和小鼠中进行感染研究,以评估RIG-I在控制reovirus感染中的作用.
主要成果:
- RIG-I与5'pp末端的病毒RNA结合并激活,包括reovirus基因组和酵母L-A病毒RNA.
- 基配5'pp-RNAs,无论其来源如何,都充当RIG-I激动剂.
- 在细胞培养和小鼠模型中,依赖于RIG-I控制reovirus感染是必不可少的.
结论:
- 对于RIG-I识别的最小决定因素是具有5'-二酸盐 (5'pp) 部分的基配对RNA.
- 对5'pp-RNA的识别扩大了RIG-I检测到的病毒结构的范围.
- 这一发现凸显了5'pp-RNA识别作为先天性免疫自我/非自我歧视病毒病原体的关键机制.
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