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Evaluating angiotensin-converting enzyme 2-mediated SARS-CoV-2 entry across species.
J Biol Chem. 2021 Jan-Jun; 296:100435.JB

Abstract

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic represents a global threat, and the interaction between the virus and angiotensin-converting enzyme 2 (ACE2), the primary entry receptor for SARS-CoV-2, is a key determinant of the range of hosts that can be infected by the virus. However, the mechanisms underpinning ACE2-mediated viral entry across species remains unclear. Using infection assay, we evaluated SARS-CoV-2 entry mediated by ACE2 of 11 different animal species. We discovered that ACE2 of Rhinolophus sinicus (Chinese rufous horseshoe bat), Felis catus (domestic cat), Canis lupus familiaris (dog), Sus scrofa (wild pig), Capra hircus (goat), and Manis javanica (Malayan pangolin) facilitated SARS-CoV-2 entry into nonsusceptible cells. Moreover, ACE2 of the pangolin also mediated SARS-CoV-2 entry, adding credence to the hypothesis that SARS-CoV-2 may have originated from pangolins. However, the ACE2 proteins of Rhinolophus ferrumequinum (greater horseshoe bat), Gallus gallus (red junglefowl), Notechis scutatus (mainland tiger snake), or Mus musculus (house mouse) did not facilitate SARS-CoV-2 entry. In addition, a natural isoform of the ACE2 protein of Macaca mulatta (rhesus monkey) with the Y217N mutation was resistant to SARS-CoV-2 infection, highlighting the possible impact of this ACE2 mutation on SARS-CoV-2 studies in rhesus monkeys. We further demonstrated that the Y217 residue of ACE2 is a critical determinant for the ability of ACE2 to mediate SARS-CoV-2 entry. Overall, these results clarify that SARS-CoV-2 can use the ACE2 receptors of multiple animal species and show that tracking the natural reservoirs and intermediate hosts of SARS-CoV-2 is complex.

Authors+Show Affiliations

State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute of Chinese Academy of Agricultural Sciences, Harbin, China.State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Disease, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China.State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Disease, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China.State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute of Chinese Academy of Agricultural Sciences, Harbin, China.State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute of Chinese Academy of Agricultural Sciences, Harbin, China.State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute of Chinese Academy of Agricultural Sciences, Harbin, China.State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute of Chinese Academy of Agricultural Sciences, Harbin, China.State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute of Chinese Academy of Agricultural Sciences, Harbin, China.School of Life Sciences and Food Engineering, Yibin University, Yibin Key Laboratory of Zoological Diversity and Ecological Conservation, Yibin, China.State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute of Chinese Academy of Agricultural Sciences, Harbin, China. Electronic address: tangyandong2008@163.com.State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Disease, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China. Electronic address: zhaojincun@gird.cn.State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute of Chinese Academy of Agricultural Sciences, Harbin, China. Electronic address: caixuehui139@163.com.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

33610551

Citation

Zhang, Hong-Liang, et al. "Evaluating Angiotensin-converting Enzyme 2-mediated SARS-CoV-2 Entry Across Species." The Journal of Biological Chemistry, vol. 296, 2021, p. 100435.
Zhang HL, Li YM, Sun J, et al. Evaluating angiotensin-converting enzyme 2-mediated SARS-CoV-2 entry across species. J Biol Chem. 2021;296:100435.
Zhang, H. L., Li, Y. M., Sun, J., Zhang, Y. Y., Wang, T. Y., Sun, M. X., Wang, M. H., Yang, Y. L., Hu, X. L., Tang, Y. D., Zhao, J., & Cai, X. (2021). Evaluating angiotensin-converting enzyme 2-mediated SARS-CoV-2 entry across species. The Journal of Biological Chemistry, 296, 100435. https://doi.org/10.1016/j.jbc.2021.100435
Zhang HL, et al. Evaluating Angiotensin-converting Enzyme 2-mediated SARS-CoV-2 Entry Across Species. J Biol Chem. 2021 Jan-Jun;296:100435. PubMed PMID: 33610551.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Evaluating angiotensin-converting enzyme 2-mediated SARS-CoV-2 entry across species. AU - Zhang,Hong-Liang, AU - Li,Yu-Ming, AU - Sun,Jing, AU - Zhang,Yu-Yuan, AU - Wang,Tong-Yun, AU - Sun,Ming-Xia, AU - Wang,Meng-Hang, AU - Yang,Yue-Lin, AU - Hu,Xiao-Liang, AU - Tang,Yan-Dong, AU - Zhao,Jincun, AU - Cai,Xuehui, Y1 - 2021/02/19/ PY - 2020/09/26/received PY - 2021/02/10/revised PY - 2021/02/16/accepted PY - 2021/2/22/pubmed PY - 2021/7/14/medline PY - 2021/2/21/entrez KW - ACE2 KW - SARS-CoV-2 KW - cross-species KW - pangolin KW - susceptibility SP - 100435 EP - 100435 JF - The Journal of biological chemistry JO - J Biol Chem VL - 296 N2 - The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic represents a global threat, and the interaction between the virus and angiotensin-converting enzyme 2 (ACE2), the primary entry receptor for SARS-CoV-2, is a key determinant of the range of hosts that can be infected by the virus. However, the mechanisms underpinning ACE2-mediated viral entry across species remains unclear. Using infection assay, we evaluated SARS-CoV-2 entry mediated by ACE2 of 11 different animal species. We discovered that ACE2 of Rhinolophus sinicus (Chinese rufous horseshoe bat), Felis catus (domestic cat), Canis lupus familiaris (dog), Sus scrofa (wild pig), Capra hircus (goat), and Manis javanica (Malayan pangolin) facilitated SARS-CoV-2 entry into nonsusceptible cells. Moreover, ACE2 of the pangolin also mediated SARS-CoV-2 entry, adding credence to the hypothesis that SARS-CoV-2 may have originated from pangolins. However, the ACE2 proteins of Rhinolophus ferrumequinum (greater horseshoe bat), Gallus gallus (red junglefowl), Notechis scutatus (mainland tiger snake), or Mus musculus (house mouse) did not facilitate SARS-CoV-2 entry. In addition, a natural isoform of the ACE2 protein of Macaca mulatta (rhesus monkey) with the Y217N mutation was resistant to SARS-CoV-2 infection, highlighting the possible impact of this ACE2 mutation on SARS-CoV-2 studies in rhesus monkeys. We further demonstrated that the Y217 residue of ACE2 is a critical determinant for the ability of ACE2 to mediate SARS-CoV-2 entry. Overall, these results clarify that SARS-CoV-2 can use the ACE2 receptors of multiple animal species and show that tracking the natural reservoirs and intermediate hosts of SARS-CoV-2 is complex. SN - 1083-351X UR - https://www.unboundmedicine.com/medline/citation/33610551/Evaluating_angiotensin_converting_enzyme_2_mediated_SARS_CoV_2_entry_across_species_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0021-9258(21)00208-8 DB - PRIME DP - Unbound Medicine ER -