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素分裂部位的损失减弱了SARS-CoV-2的病原性

Bryan A Johnson¹, Xuping Xie², Adam L Bailey³

¹Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, USA.

|January 25, 2021

概括

SARS-CoV-2 素分裂部位对于感染和病变产生至关重要. 删除该部位 (ΔPRRA突变) 减少了疾病的严重程度,但仍能对SARS-CoV-2进行保护.

科学领域:

病毒学
病变发生
免疫学

背景情况:

严重急性呼吸道综合征冠状病毒2 (SARS-CoV-2) 导致全球大流行.
SARS-CoV-2在其尖端蛋白中具有独特的素分裂部位 (PRRAR),而相关的冠状病毒中则没有这种部位.
在病毒感染和疾病中,这种素分裂部位的作用尚未完全阐明.

研究的目的:

调查SARS-CoV-2素分裂部位对病毒感染和病变的贡献.
为了生成和特征SARS-CoV-2突变缺少素分裂部位 (ΔPRRA).

主要方法:

产生一种缺乏素分裂部位的SARS-CoV-2突变体 (ΔPRRA).
在细胞培养中评估病毒复制动力学和适应性 (Vero E6,人类呼吸细胞).
在动物模型中评估病毒病原性 (驼鹿,K18-hACE2转基因小鼠).
对野生型和突变病毒的抗体中和分析.

主要成果:

在Vero E6细胞中,ΔPRRA突变体表现出更快的复制动力和更好的适应性,但在人类呼吸细胞中复制减少.
在子和K18- hACE2小鼠模型中,ΔPRRA突变被减弱,显示疾病减少.
尽管病原性降低,但 ΔPRRA 突变使得对随后的 SARS-CoV-2 具有保护性.
COVID-19 患者血清和单克隆抗体的中和度较低,对抗 ΔPRRA 突变.

结论:

素分裂部位在SARS-CoV-2感染和发病过程中起着至关重要的作用.
素分裂部位对于评估抗体对SARS-CoV-2的中和活性很重要.
针对或了解素分裂部位对于开发有效的COVID-19疗法和诊断至关重要.

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