SARS-CoV-2 劫持细胞损伤反应,从而诱导更高效的 Spike S-acyltransferase 的转录
Francisco S Mesquita1, Laurence Abrami2, Lucie Bracq2
1Global Health Institute, School of Life Sciences, EPFL, Lausanne, Switzerland. francisco.mesquita@epfl.ch.
Nature communications
|November 11, 2023
概括
通过改变ZDHHC20基因,SARS-CoV-2感染增强了病毒融合. 这会产生更活跃的酶,增强Spike蛋白的S-化,改善病毒与宿主细胞的融合.
科学领域:
- 病毒学 病毒学
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
背景情况:
- SARS-CoV-2 病毒的进入依赖于Spike 蛋白质介导的膜融合.
- 尖端蛋白的融合活性是由宿主S-转移酶调节的,特别是ZDHHC20.
- 与单独的传染相比,SARS-CoV-2感染增加了尖端蛋白S-化.
研究的目的:
- 为了研究SARS-CoV-2感染期间斯派克蛋白S-化增加背后的机制.
- 为了确定SARS-CoV-2感染是否会改变ZDHHC20的表达或活性.
- 探索ZDHHC20修饰对病毒融合的功能影响.
主要方法:
- 在感染细胞和体内模型中分析zdhhc20基因转录起始部位的变化.
- 对N端扩展ZDHHC20蛋白的S-化活性进行评估.
- 在不同条件下的病毒宿主细胞融合效率的量化.
主要成果:
- 感染SARS-CoV-2会导致zdhhc20基因的转录开始部位发生变化.
- 这导致一个N端扩展的ZDHHC20蛋白,具有~40倍高的Spike化活性.
- 修改后的ZDHHC20增强了病毒与宿主细胞膜融合.
- 在对化学诱导的大肠炎和毛孔形成毒素的反应中观察到类似的转录变化.
结论:
- SARS-CoV-2 感染劫持了一条涉及 ZDHHC20.20 的细胞损伤反应途径.
- 该病毒诱导一种更活跃的ZDHHC20形式,以优化Spike蛋白的S-化,并增强病毒融合.
- 这种机制突出了对病毒感染性至关重要的宿主-病原体相互作用.
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