在SARS-CoV-2和型EV-D68编码蛋白酶中,分别调节了热灭菌的发生
Siyu Shen1, Haoran Guo1, Yan Li1
1Institute of Virology and AIDS Research, First Hospital, Jilin University, Changchun, Jilin, China.
Journal of virology
|January 30, 2024
概括
来自SARS-CoV-2和EV-D68的病毒蛋白酶通过向气体皮质蛋白来差异调节热. 这项研究揭示了这些病毒如何操纵细胞死亡,为抗病毒和癌症疗法提供了洞察力.
科学领域:
- 分子生物学分子生物学
- 病毒学 病毒学
- 免疫学 免疫学 免疫学
背景情况:
- 炎症性编程细胞死亡的Pyroptosis与病毒病原发生有关,包括2019年新冠肺炎疾病 (COVID-19).
- 气体胺家族蛋白质 (GSDMs),特别是GSDMD和GSDME,是热的关键作用因子.
- 病毒调节热的机制尚不完全理解.
研究的目的:
- 选病毒蛋白质以检测它们干扰GSDMD定位和功能的能力.
- 为了阐明SARS-CoV-2和EV-D68蛋白酶如何调节GSDM介导的热.
- 为了研究EV-D68感染的潜在瘤效应.
主要方法:
- 在活细胞中使用mCherry-GSDMD光记者试验进行高通量选.
- 研究了SARS-CoV-2蛋白酶 (NSP5,NSP3) 在GSDMD和GSDME上的分裂部位和功能后果.
- 检查了EV-D68蛋白酶 (3C,2A) 对GSDMD和GSDME功能和火灭菌诱导的影响.
主要成果:
- SARS-CoV-2 主蛋白酶NSP5通过在Q29和Q193.3处裂解GSDMD,抑制了GSDMD介导的烧.
- SARS-CoV-2 蛋白酶 NSP3 激活了 GSDME 通过在 G370.0 处裂解 GSDME 的 GSDME 介导的灭.
- EV-D68蛋白酶3C和2A不激活了GSDMD,同时启动了与SARS-CoV-2蛋白酶相似的GSDME介导的烧灭酶.
- EV-D68感染诱导了 pyroptotic 细胞死亡,并对人类癌细胞表现出致癌作用.
结论:
- 呼吸系统病毒,包括SARS-CoV-2和EV-D68,具有独特的蛋白酶,可以差异调节宿主细胞灭.
- 对GSDMD和GSDME途径的病毒操纵为病毒病原和宿主免疫反应提供了洞察力.
- 这些发现表明抗病毒策略和癌症治疗的潜在治疗点,特别是利用EV-D68的瘤治疗特性.
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