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

doi:10.3969/j.issn.1006-7795.2022.03.015

首都医科大学学报 ›› 2022, Vol. 43 ›› Issue (3): 421-426.doi: 10.3969/j.issn.1006-7795.2022.03.015

• 新型冠状病毒肺炎:基础研究到临床诊治 • 上一篇下一篇

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

邱雅若^1#, 李星霖^2#, 陈丹瑛², 刘永梅², 宋焱君², 李国力², 宋川², 王玺², 赵学森^1*

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

收稿日期:2022-03-20 出版日期:2022-06-21 发布日期:2022-06-01
作者简介:^#共同第一作者
基金资助:
国家自然科学基金(81971916)。

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

Qiu Yaruo^1#, Li Xinglin^2#, Chen Danying², Liu Yongmei², Song Yanjun², Li Guoli², Song Chuan², Wang Xi², Zhao Xuesen^1*

1. Peking University Ditan Teaching Hospital, Beijing 100015, China;
2. Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China

Received:2022-03-20 Online:2022-06-21 Published:2022-06-01
Contact: *E-mail:zhaoxuesen@ccmu.edu.cn
Supported by:
National Natural Science Foundation of China (81971916).

摘要/Abstract

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 enzyme Ⅱ, 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。

关键词: 新型冠状病毒, Omicron, 血管紧张素转换酶Ⅱ

Abstract: Objective To investigate the ability of Omicron variant of SARS-CoV-2 to utilize angiotensin-converting enzyme Ⅱ(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.

Key words: severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2), Omicron, angiotensin-converting enzyme Ⅱ

中图分类号:

R563.1

邱雅若, 李星霖, 陈丹瑛, 刘永梅, 宋焱君, 李国力, 宋川, 王玺, 赵学森. 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[J]. 首都医科大学学报, 2022, 43(3): 421-426.

Qiu Yaruo, Li Xinglin, Chen Danying, Liu Yongmei, Song Yanjun, Li Guoli, Song Chuan, Wang Xi, Zhao Xuesen. Ability of Omicron variant of SARS-CoV-2 to utilize angiotensin-converting enzyme Ⅱ from different animals as receptors for cellular entry[J]. Journal of Capital Medical University, 2022, 43(3): 421-426.

参考文献

[1] Okba N M A, Müller M A, Li W T, et al. Severe acute respiratory syndrome coronavirus 2-specific antibody responses in coronavirus disease patients[J]. Emerg Infect Dis, 2020, 26(7): 1478-1488.
[2] Li Q, Guan X H, Wu P, et al. Early transmission dynamics in Wuhan, China, of novel coronavirus-infected pneumonia[J]. N Engl J Med, 2020, 382(13): 1199-1207.
[3] Wang M Y, Zhao R, Gao L J, et al. SARS-CoV-2: structure, biology, and structure-based therapeutics development[J]. Front Cell Infect Microbiol, 2020, 10: 587269.
[4] Hoffmann M, Krüger N, Schulz S, et al. The Omicron variant is highly resistant against antibody-mediated neutralization: implications for control of the COVID-19 pandemic[J]. Cell, 2022, 185(3): 447-456.e11.
[5] Zhao X S, Chen D Y, Szabla R, et al. Broad and differential animal angiotensin-converting enzyme 2 receptor usage by SARS-CoV-2[J]. J Virol, 2020, 94(18): e00940-e00920.
[6] Callaway E. Heavily mutated Omicron variant puts scientists on alert[J]. Nature, 2021, 600(7887): 21.
[7] Zhang L, Li Q Q, Liang Z T, et al. The significant immune escape of pseudotyped SARS-CoV-2 variant Omicron[J]. Emerg Microbes Infect, 2022, 11(1): 1-5.
[8] Araf Y, Akter F, Tang Y D, et al. Omicron variant of SARS-CoV-2: genomics, transmissibility, and responses to current COVID-19 vaccines[J]. J Med Virol, 2022, 94(5): 1825-1832.
[9] Planas D, Veyer D, Baidaliuk A, et al. Reduced sensitivity of SARS-CoV-2 variant delta to antibody neutralization[J]. Nature, 2021, 596(7871): 276-280.
[10] Han P C, Li L J, Liu S, et al. Receptor binding and complex structures of human ACE2 to spike RBD from omicron and delta SARS-CoV-2[J]. Cell, 2022, 185(4): 630-640.e10.
[11] Du P, Gao G F, Wang Q H. The mysterious origins of the Omicron variant of SARS-CoV-2[J]. Innovation (N Y), 2022, 3(2): 100206.
[12] Wei C S, Shan K J, Wang W G, et al. Evidence for a mouse origin of the SARS-CoV-2 Omicron variant[J]. J Genet Genomics, 2021, 48(12): 1111-1121.
[13] Bojkova D, Klann K, Koch B, et al. SARS-CoV-2 infected host cell proteomics reveal potential therapy targets[J]. Nature, 2020, 583: 469-472.
[14] Davidson A D, Williamson M K , Lewis S, et al. Characterisation of the transcriptome and proteome of SARS-CoV-2 reveals a cell passage induced in-frame deletion of the furin-like cleavage site from the spike glycoprotein[J]. Genome Med, 2020, 12(1): 68.
[15] Hoffmann M, Kleine-Weber H, Schroeder S, et al. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor[J]. Cell, 2020, 181(2): 271-280.e8.
[16] Chen J H, Wang R, Gilby N B, et al. Omicron variant (B.1.1.529): infectivity, vaccine breakthrough, and antibody resistance[J]. J Chem Inf Model, 2022, 62(2): 412-422.

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 enzyme Ⅱ from different animals as receptors for cellular entry

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