通过ATM/ATR介导的DNA损伤反应促进了SARS-CoV-2尖端蛋白诱导的同位素形成
Xiaotong Zhao1, Tingting Wei1, Yujia Hou1
1Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, State Key Laboratory of Advanced Medical Materials and Devices, Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China.
Journal of medical virology
|December 31, 2024
概括
通过激活DNA损伤反应 (DDR) 途径,SARS-CoV-2尖端蛋白诱导细胞融合. 抑制像ATM和ATR这样的DDR激酶会减少合成细胞的形成,这表明病毒利用宿主DDR进行传播.
科学领域:
- 病毒学 病毒学
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
背景情况:
- 在SARS-CoV-2感染的肺部中观察到多核细胞 (syncytia).
- SARS-CoV-2尖端蛋白调解细胞融合,但宿主反应和DNA损伤反应 (DDR) 的作用尚不清楚.
研究的目的:
- 在体外研究SARS-CoV-2尖端蛋白对细胞融合的影响.
- 确定DDR信号传导 (ATR/ATM激酶) 在尖端蛋白诱导的突触形成中的作用.
主要方法:
- 在实验室中使用了表达ACE2的同源和异源细胞融合模型.
- 分析了ATR,ATM,CHK1,CHK2和DDR标记物的蛋白质水平 (γH2AX,53BP1,RAD51).
- 利用siRNA和激酶抑制剂 (ATM,ATR) 来评估它们对合成细胞形成的影响.
主要成果:
- 细胞融合激活了ATR-CHK1和ATM-CHK2信号通路.
- 在Syncytia中,DDR标记物 γH2AX,53BP1和RAD51.1的聚合被发现.
- 抑制ATM和ATR抑制了合成细胞的形成,并降低了S蛋白水平.
结论:
- 主体DNA损伤反应 (DDR) 在稳定SARS-CoV-2尖端蛋白中起着至关重要的作用.
- DDR信号促进了尖端蛋白诱导的细胞融合和同位素的形成.
- SARS-CoV-2 似乎利用宿主 DDR 途径促进病毒传播.
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