由CARD8炎症酶体对冠状病毒和皮科纳病毒的宿主特异感应
Brian V Tsu1, Rimjhim Agarwal1, Nandan S Gokhale2
1Department of Molecular Biology, University of California, San Diego, La Jolla, California, United States of America.
PLoS biology
|June 8, 2023
概括
冠状病毒 冠状病毒
科学领域:
- 免疫学 免疫学 免疫学
- 病毒学 病毒学
- 分子生物学分子生物学
背景情况:
- 主体免疫反应涉及通过NLRP1和CARD8.8等炎症体传感器检测微生物蛋白酶.
- 冠状病毒,包括SARS-CoV-2,编码3CL蛋白酶 (3CLpro),对病毒复制至关重要.
研究的目的:
- 为了研究冠状病毒3CLpro和人类CARD8炎症体传感器之间的相互作用.
- 探索CARD8中的自然变异如何影响其对病毒蛋白酶的感知.
主要方法:
- 在体外测试以评估CARD8裂变和病毒蛋白酶的炎症酶激活.
- 分析CARD8序列变异及其功能后果.
主要成果:
- 人类的CARD8直接分裂并被冠状病毒3CLpro激活,在SARS-CoV-2感染期间触发炎症体反应,细胞死亡和细胞因子释放.
- 自然的CARD8变异改变了3CLpro的感知,一些变异显示了对抗性或感知了不同的病毒蛋白酶 (例如,picornavirus3Cpro).
结论:
- CARD8充当病毒蛋白酶活性的广泛传感器,包括冠状病毒3CLpro.
- 在CARD8的遗传多样性影响宿主病毒相互作用,有助于病毒传感和免疫病理学在物种之间变化的变化.
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