由SARS-CoV-2增强的先天免疫逃避的演变
Lucy G Thorne1, Mehdi Bouhaddou2,3,4,5, Ann-Kathrin Reuschl1
1Division of Infection and Immunity, University College London, London, UK.
Nature
|December 23, 2021
概括
由于核体蛋白 (N),Orf9b和Orf6的水平增加,SARS-CoV-2 Alpha变种更有效地抑制免疫反应. 这些病毒抗剂增强了传播,并可能增加感染的持续时间.
科学领域:
- 病毒学
- 免疫学
- 分子生物学
背景情况:
- 引起关注的SARS-CoV-2变种表现出适应性,可增强人与人之间的传播.
- 专注于尖端蛋白突变,但非尖端突变可能有助于病毒适应.
研究的目的:
- 调查SARS-CoV-2阿尔法变异突变在尖端蛋白外对先天免疫抑制的影响.
- 阐明阿尔法变异增强病毒传播和复制的机制.
主要方法:
- 没有偏见的丰度蛋白质组学,蛋白质组学和RNA测序.
- 在呼吸道上皮细胞中进行病毒复制测试.
- 研究了Orf9b与线粒体蛋白TOM70的相互作用及其在先天免疫激活中的作用.
主要成果:
- 与第一波隔离物相比,阿尔法变异隔离物显示出增强的先天免疫反应抑制.
- 在阿尔法变体中显著增加核体蛋白 (N),Orf9b和Orf6.
- 通过与MAVS激活的关键调节者TOM70的相互作用,Orf9b抑制了先天免疫力.
- 通过酸化调节Orf9b-TOM70的相互作用.
结论:
- 像Orf9b这样的病毒免疫抗剂的增强表达有助于阿尔法变异的传染性增加.
- 在尖端蛋白之外的突变,特别是在N和Orf9b调节区域,对于SARS-CoV-2的适应至关重要.
- 德尔塔和欧米克朗变异的类似突变凸显了非尖端适应对病毒进化的意义.
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