SARS-CoV-2不同毒株在K18-hACE2小鼠体内的毒力比较  

Comparison of virulence of different SARS-CoV-2 strains in K18-hACE2 mice

作　　者：张秋 王如玉 范慧芬 孙凯丽 刘元浪 夏云翔 徐秀丽 卢佳 李新国 ZHANG Qiu;WANG Ruyu;FAN Huifen;SUN Kaili;LIU Yuanlang;XIA Yunxiang;XU Xiuli;LU Jia;LI Xinguo(Wuhan Institute of Biological Products Co.,Ltd.,Wuhan 430207,Hubei Province,China)

机构地区：[1]武汉生物制品研究所有限责任公司,湖北武汉430207

出　　处：《中国生物制品学杂志》2023年第12期1455-1464,共10页Chinese Journal of Biologicals

基　　金：国家重点研发计划(2020YFC0842100,2020YFC0841800)。

摘　　要：目的通过滴鼻途径探讨严重急性呼吸系统综合征冠状病毒2(severe acute respiratory syndrome coronavirus 2,SARS-CoV-2)不同毒株(Prototype、Delta、Beta、Omicron BA.1)对表达人血管紧张素转换酶2(angiotensin-converting enzyme 2,ACE2)的转基因小鼠K18-hACE2的感染效果。方法每种毒株设置不同梯度的攻毒剂量,采用滴鼻方式进行攻毒,每日监测小鼠体质量及存活情况,观察周期变异株Beta组为6 d,其他3组为14 d。利用IBM SPSS Statistics26分析软件计算半数致死量(LD_(50)),通过检测肺、脑、鼻甲组织病毒核酸载量及肺组织病变损伤情况对SARS-CoV-2不同毒株的毒力进行比较。结果Beta株毒力最强、致死性最高,最低剂量(1 CCID_(50))100%致死,LD_(50)<1 CCID_(50);Delta、Prototype和Omicron BA.1株的LD_(50)分别为0.52、0.60和52.92 CCID_(50)。不同毒株感染后各剂量组小鼠的肺组织病毒核酸拷贝数随着攻毒剂量的增加而呈整体递增趋势,死亡小鼠的脑组织病毒拷贝数可达10^(8)~10^(11)copies/mL,感染不同毒株各剂量组小鼠的肺组织病理出现不同程度的损伤。结论SARS-CoV-2不同毒株在K18-hACE2小鼠体内的毒力Beta>Delta>Prototype>Omicron BA.1。Objective To investigate the infection effects of different strains(Prototype,Delta,Beta,and Omicron BA.1)of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)on transgenic mice K18-hACE2 expressing angiotensinconverting enzyme 2(ACE2)by nasal drip.MethodsMice were challenged with each strain of different gradients of doses by nasal drip,which were monitored for body mass and survival daily for 6 d in Beta group and 14 d in the other three groups.The median lethal dose(LD_(50))was calculated by IBM SPSS Statistics 26 analysis software,and the virulence of different SARS-CoV-2 strains were compared by detection of the viral nucleic acid loads of lung,brain and turbinate tissues and the lesion of lung tissues.ResultsBeta strain showed the strongest virulence and the highest lethality,and the lowest dose(1 CCID_(50))was 100%lethal with a LD_(50)less than 1 CCID_(50);The LD_(50)of Delta,Prototype and Omicron BA.1 strains were 0.52,0.60 and 52.92 CCID50respectively.The copy number of viral nucleic acid in lung tissue of mice infected with different strains elevated with the increase of challenge dose,and the copy number of viral nucleic acid in brain tissue of dead mice reached 10^(8)~10^(11)copies/mL.The lung tissues of mice infected with different strains of different doses showed different degrees of pathological damage.ConclusionThe virulence of different SARS-CoV-2 strains in K18-hACE2 mice from high to low were Beta,Delta,Prototype and Omicron BA.1.

关 键 词：严重急性呼吸系统综合征冠状病毒2 变异株 K18-hACE2小鼠 半数致死量 病毒核酸载量 病理检测 

分 类 号：R563.1[医药卫生—呼吸系统] R-332[医药卫生—内科学]