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SARS-CoV-2 蛋白 ORF3c 是先天免疫力的线粒体调节器
Hazel Stewart1, Yongxu Lu1, Sarah O'Keefe2
1Department of Pathology, University of Cambridge, Cambridge, UK.
iScience
|October 20, 2023
概括
SARS-CoV-2辅助蛋白ORF3c通过向线粒体中的MAVS来抑制先天免疫力,限制干扰素β的产生并帮助病毒免疫逃避.
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:
- 在SARS-CoV-2基因组编码辅助蛋白质,包括预测ORF3c.
- 在SARS-CoV和SARS-CoV-2中存在ORF3c,但其功能尚不清楚.
- 核糖体分析证实了感染期间ORF3c的表达.
研究的目的:
- 为了研究SARS-CoV-2辅助蛋白ORF3c.的功能.
- 阐明ORF3c与宿主免疫系统相互作用的机制.
主要方法:
- 进行比较基因组学来预测ORF3c.
- 核糖体分析以确认ORF3c的表达.
- 亚细胞局部化研究 (线粒体).
- 免疫信号测试 (IFN-β,NF-κB,JAK-STAT) 进行.
- 同免疫沉和蛋白质裂变测试.
主要成果:
- ORF3c局部化到线粒体中.
- ORF3c限制了IFN-β的产生,但不限制NF-κB或JAK-STAT的信号传输.
- ORF3c抑制了涉及RIG-I,MDA5和MAVS的途径,但不是TRIF,TBK1或IRF3.3的途径.
- ORF3c与MAVS和PGAM5.5一起进行共免疫沉.
- 在ORF3c中,ORF3c通过caspase-3诱导MAVS裂变.
结论:
- SARS-CoV-2 ORF3c是一种线粒体蛋白质,可以抑制天生的免疫力.
- ORF3c通过分裂抗病毒适应蛋白MAVS.来逃避宿主防御.
- 这种机制有助于SARS-CoV-2的免疫逃避.
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