新型冠状病毒Omicron变异株利用多种动物ACE2作为受体侵入细胞的能力  

Ability of Omicron variant of SARS-CoV-2 to utilize angiotensin-converting enzymeⅡfrom different animals as receptors for cellular entry

作　　者：邱雅若 李星霖 陈丹瑛 刘永梅 宋焱君 李国力[2] 宋川[2] 王玺 赵学森[1] Qiu Yaruo;Li Xinglin;Chen Danying;Liu Yongmei;Song Yanjun;Li Guoli;Song Chuan;Wang Xi;Zhao Xuesen(Peking University Ditan Teaching Hospital, Beijing 100015, China;Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China)

机构地区：[1]北京大学地坛医院教学医院,北京100015 [2]首都医科大学附属北京地坛医院传染病研究所,北京100015

出　　处：《首都医科大学学报》2022年第3期421-426,共6页Journal of Capital Medical University

基　　金：国家自然科学基金(81971916)。

摘　　要：目的探讨新型冠状病毒Omicron变异株利用不同动物血管紧张素转换酶Ⅱ(angiotensin-converting enzymeⅡ,ACE2)受体侵入细胞的能力,评价Omicron变异株潜在的跨宿主传播风险。方法将不同动物来源的ACE2表达质粒转染至293T细胞,建立新型冠状病毒D614G株系、Delta株系及Omicron株系的假病毒感染系统,并进行假病毒感染实验;利用假病毒感染系统及荧光酶素报告基因检测Omicron刺突蛋白对不同动物来源的ACE2受体利用能力。结果与D614G株相比,Omicron株利用小鼠ACE2受体侵入细胞的能力明显增高(t=16.09、P<0.05),但其利用中华菊头蝠、墨西哥无尾蝠、雪貂獾、猪獾、猫、兔、穿山甲的ACE2受体侵入细胞的能力降低(t=17.80、P<0.05,t=8.43、P<0.05,t=18.10、P<0.05,t=10.46、P<0.05,t=22.00、P<0.05,t=10.08、P<0.05,t=4.83、P<0.05);与Delta株相比,Omicron株利用中华菊头蝠、雪貂獾、猪獾、猫的ACE2受体侵入细胞的能力降低(t=8.15、P<0.05,t=7.91、P<0.05,t=8.59、P<0.05,t=8.43、P<0.05)。结论新型冠状病毒Omicron株的刺突蛋白可以利用多种动物的ACE2作为受体感染细胞,提示Omicron株可能存在多种跨宿主传播的风险。Objective To investigate the ability of Omicron variant of SARS-CoV-2 to utilize angiotensin-converting enzymeⅡ(ACE2)from different animals as receptors for cellular entry,and to explore the potential cross-species transmissibility of Omicron.Methods Plasmids encoding ACE2 molecules from different animals were constructed and transfected into 293T cells.The pseudoviral infection systems of D614G strain,Delta strain and Omicron strain were established to determine receptor activity of different animals’ACE2 for cellular entry.The utilization ability of Omicron strain to ACE2 receptors were examined by luciferase assay.Results ACE2 from different animals expressed in 293T cells supported cellular entry mediated by spike protein.Compared with D614G,the ability of Omicron-pp to invade cells using mouse ACE2 molecules was significantly increased(t=16.09,P<0.05),while it decreased when using ACE2 molecules from Chinese horseshoe bat,Mexican free-tailed bat,Ferret badger,Hog badger,Feline,Rabbit,or Pangolin(t=17.80,P<0.05;t=8.43,P<0.05;t=18.10,P<0.05;t=10.46,P<0.05;t=22.00,P<0.05;t=10.08,P<0.05;t=4.83,P<0.05,respectively).Compared with Delta,the ability of Omicron-pp to entry cells was decreased when using Chinese horseshoe bat,Ferret badger,Hog badger and Feline(t=8.15,P<0.05;t=7.91,P<0.05;t=8.59,P<0.05;t=8.43,P<0.05,respectively).Conclusion The ACE2 molecules from different animals served as functional receptors for cellular entry mediated by Omicron spike protein.Our findings herein suggest that there may exist a risk of multiple cross-species transmission of Omicron among different mammal animals.

关 键 词：新型冠状病毒 Omicron 血管紧张素转换酶Ⅱ 

分 类 号：R563.1[医药卫生—呼吸系统]