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The 442th amino acid residue of the spike protein is critical for the adaptation to bat hosts for SARS-related coronaviruses.
Virus Res. 2021 04 02; 295:198307.VR

Abstract

Bats carry diverse severe acute respiratory syndrome-related coronaviruses (SARSr-CoVs). The suspected interspecies transmission of SARSr-CoVs from bats to humans has caused two severe CoV pandemics, the SARS pandemic in 2003 and the recent COVID-19 pandemic. The receptor utilization of SARSr-CoV plays the key role in determining the host range and the interspecies transmission ability of the virus. Both SARS-CoV and SARS-CoV-2 use angiotensin-converting enzyme 2 (ACE2) as their receptor. Previous studies showed that WIV1 strain, the first living coronavirus isolated from bat using ACE2 as its receptor, is the prototype of SARS-CoV. The receptor-binding domain (RBD) in the spike protein (S) of SARS-CoV and WIV1 is responsible for ACE2 binding and medicates the viral entry. Comparing to SARS-CoV, WIV1 has three distinct amino acid residues (442, 472, and 487) in its RBD. This study aimed at exploring whether these three residues could alter the receptor utilization of SARSr-CoVs. We replaced the three residues in SARS-CoV (BJ01 strain) S with their counterparts in WIV1 S, and then evaluated the change of their utilization of bat, civet, and human ACE2s using a lentivirus-based pseudovirus infection system. To further validate the S-ACE2 interactions, the binding affinity between the RBDs of these S proteins and the three ACE2s were verified by flow cytometry. The results showed that the single amino acid substitution Y442S in the RBD of BJ01 S enhanced its utilization of bat ACE2 and its binding affinity to bat ACE2. On the contrary, the reverse substitution in WIV1 S (S442Y) significantly attenuated the pseudovirus utilization of bat, civet and human ACE2s for cell entry, and reduced its binding affinity with the three ACE2s. These results suggest that the S442 is critical for WIV1 adapting to bats as its natural hosts. These findings will enhance our understanding of host adaptations and cross-species infections of coronaviruses, contributing to the prediction and prevention of coronavirus epidemics.

Authors+Show Affiliations

Hunan Provincial Key Laboratory of Medical Virology, Institute of Pathogen Biology and Immunology, College of Biology, Hunan University, 27 Tianma Rd., Changsha, Hunan, 410012, China. Electronic address: lijinyan@hnu.edu.cn.Hunan Provincial Key Laboratory of Medical Virology, Institute of Pathogen Biology and Immunology, College of Biology, Hunan University, 27 Tianma Rd., Changsha, Hunan, 410012, China. Electronic address: qw@hnu.edu.cn.Hunan Provincial Key Laboratory of Medical Virology, Institute of Pathogen Biology and Immunology, College of Biology, Hunan University, 27 Tianma Rd., Changsha, Hunan, 410012, China. Electronic address: liaoceheng@hnu.edu.cn.Hunan Provincial Key Laboratory of Medical Virology, Institute of Pathogen Biology and Immunology, College of Biology, Hunan University, 27 Tianma Rd., Changsha, Hunan, 410012, China. Electronic address: qiuye@hnu.edu.cn.Hunan Provincial Key Laboratory of Medical Virology, Institute of Pathogen Biology and Immunology, College of Biology, Hunan University, 27 Tianma Rd., Changsha, Hunan, 410012, China. Electronic address: xyge@hnu.edu.cn.

Pub Type(s)

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

Language

eng

PubMed ID

33476695

Citation

Li, Jin-Yan, et al. "The 442th Amino Acid Residue of the Spike Protein Is Critical for the Adaptation to Bat Hosts for SARS-related Coronaviruses." Virus Research, vol. 295, 2021, p. 198307.
Li JY, Wang Q, Liao CH, et al. The 442th amino acid residue of the spike protein is critical for the adaptation to bat hosts for SARS-related coronaviruses. Virus Res. 2021;295:198307.
Li, J. Y., Wang, Q., Liao, C. H., Qiu, Y., & Ge, X. Y. (2021). The 442th amino acid residue of the spike protein is critical for the adaptation to bat hosts for SARS-related coronaviruses. Virus Research, 295, 198307. https://doi.org/10.1016/j.virusres.2021.198307
Li JY, et al. The 442th Amino Acid Residue of the Spike Protein Is Critical for the Adaptation to Bat Hosts for SARS-related Coronaviruses. Virus Res. 2021 04 2;295:198307. PubMed PMID: 33476695.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The 442th amino acid residue of the spike protein is critical for the adaptation to bat hosts for SARS-related coronaviruses. AU - Li,Jin-Yan, AU - Wang,Qiong, AU - Liao,Ce-Heng, AU - Qiu,Ye, AU - Ge,Xing-Yi, Y1 - 2021/01/18/ PY - 2020/09/08/received PY - 2021/01/12/revised PY - 2021/01/13/accepted PY - 2021/1/22/pubmed PY - 2021/3/24/medline PY - 2021/1/21/entrez KW - ACE2 KW - Receptor binding domain KW - Receptor utilization KW - SARS-CoV KW - SARSr-CoV KW - Spike SP - 198307 EP - 198307 JF - Virus research JO - Virus Res VL - 295 N2 - Bats carry diverse severe acute respiratory syndrome-related coronaviruses (SARSr-CoVs). The suspected interspecies transmission of SARSr-CoVs from bats to humans has caused two severe CoV pandemics, the SARS pandemic in 2003 and the recent COVID-19 pandemic. The receptor utilization of SARSr-CoV plays the key role in determining the host range and the interspecies transmission ability of the virus. Both SARS-CoV and SARS-CoV-2 use angiotensin-converting enzyme 2 (ACE2) as their receptor. Previous studies showed that WIV1 strain, the first living coronavirus isolated from bat using ACE2 as its receptor, is the prototype of SARS-CoV. The receptor-binding domain (RBD) in the spike protein (S) of SARS-CoV and WIV1 is responsible for ACE2 binding and medicates the viral entry. Comparing to SARS-CoV, WIV1 has three distinct amino acid residues (442, 472, and 487) in its RBD. This study aimed at exploring whether these three residues could alter the receptor utilization of SARSr-CoVs. We replaced the three residues in SARS-CoV (BJ01 strain) S with their counterparts in WIV1 S, and then evaluated the change of their utilization of bat, civet, and human ACE2s using a lentivirus-based pseudovirus infection system. To further validate the S-ACE2 interactions, the binding affinity between the RBDs of these S proteins and the three ACE2s were verified by flow cytometry. The results showed that the single amino acid substitution Y442S in the RBD of BJ01 S enhanced its utilization of bat ACE2 and its binding affinity to bat ACE2. On the contrary, the reverse substitution in WIV1 S (S442Y) significantly attenuated the pseudovirus utilization of bat, civet and human ACE2s for cell entry, and reduced its binding affinity with the three ACE2s. These results suggest that the S442 is critical for WIV1 adapting to bats as its natural hosts. These findings will enhance our understanding of host adaptations and cross-species infections of coronaviruses, contributing to the prediction and prevention of coronavirus epidemics. SN - 1872-7492 UR - https://www.unboundmedicine.com/medline/citation/33476695/The_442th_amino_acid_residue_of_the_spike_protein_is_critical_for_the_adaptation_to_bat_hosts_for_SARS_related_coronaviruses_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0168-1702(21)00014-9 DB - PRIME DP - Unbound Medicine ER -