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Receptor Usage of a Novel Bat Lineage C Betacoronavirus Reveals Evolution of Middle East Respiratory Syndrome-Related Coronavirus Spike Proteins for Human Dipeptidyl Peptidase 4 Binding.
J Infect Dis. 2018 06 20; 218(2):197-207.JI

Abstract

Although bats are known to harbor Middle East Respiratory Syndrome coronavirus (MERS-CoV)-related viruses, the role of bats in the evolutionary origin and pathway remains obscure. We identified a novel MERS-CoV-related betacoronavirus, Hp-BatCoV HKU25, from Chinese pipistrelle bats. Although it is closely related to MERS-CoV in most genome regions, its spike protein occupies a phylogenetic position between that of Ty-BatCoV HKU4 and Pi-BatCoV HKU5. Because Ty-BatCoV HKU4 but not Pi-BatCoV HKU5 can use the MERS-CoV receptor human dipeptidyl peptidase 4 (hDPP4) for cell entry, we tested the ability of Hp-BatCoV HKU25 to bind and use hDPP4. The HKU25-receptor binding domain (RBD) can bind to hDPP4 protein and hDPP4-expressing cells, but it does so with lower efficiency than that of MERS-RBD. Pseudovirus assays showed that HKU25-spike can use hDPP4 for entry to hDPP4-expressing cells, although with lower efficiency than that of MERS-spike and HKU4-spike. Our findings support a bat origin of MERS-CoV and suggest that bat CoV spike proteins may have evolved in a stepwise manner for binding to hDPP4.

Authors+Show Affiliations

State Key Laboratory of Emerging Infectious Diseases The University of Hong Kong, China. Department of Microbiology The University of Hong Kong, China. Carol Yu Centre for Infection The University of Hong Kong, China. Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Li Ka Shing Faculty of Medicine, The University of Hong Kong, China.Guangdong Key Laboratory of Animal Conservation and Resource Utilization, Guangdong Public Laboratory of Wild Animal Conservation and Utilization, and Guangdong Institute of Applied Biological Resources, Guangzhou, Guangdong Province, China.Department of Microbiology The University of Hong Kong, China.Department of Microbiology The University of Hong Kong, China.Guangdong Key Laboratory of Animal Conservation and Resource Utilization, Guangdong Public Laboratory of Wild Animal Conservation and Utilization, and Guangdong Institute of Applied Biological Resources, Guangzhou, Guangdong Province, China.Department of Microbiology The University of Hong Kong, China.Guangdong Key Laboratory of Animal Conservation and Resource Utilization, Guangdong Public Laboratory of Wild Animal Conservation and Utilization, and Guangdong Institute of Applied Biological Resources, Guangzhou, Guangdong Province, China.Department of Microbiology The University of Hong Kong, China.Department of Microbiology The University of Hong Kong, China.Department of Microbiology The University of Hong Kong, China.Department of Microbiology The University of Hong Kong, China.Department of Microbiology The University of Hong Kong, China.State Key Laboratory of Emerging Infectious Diseases The University of Hong Kong, China. Department of Microbiology The University of Hong Kong, China. Carol Yu Centre for Infection The University of Hong Kong, China. Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Li Ka Shing Faculty of Medicine, The University of Hong Kong, China.National Institute of Biological Sciences, Zhongguancun Life Science Park, Changping, Beijing, China.School of Biomedical Sciences, The University of Hong Kong, China.State Key Laboratory of Emerging Infectious Diseases The University of Hong Kong, China. Department of Microbiology The University of Hong Kong, China. Carol Yu Centre for Infection The University of Hong Kong, China. Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Li Ka Shing Faculty of Medicine, The University of Hong Kong, China.Department of Biomedical Sciences, City University of Hong Kong, China.State Key Laboratory of Emerging Infectious Diseases The University of Hong Kong, China. Department of Microbiology The University of Hong Kong, China. Carol Yu Centre for Infection The University of Hong Kong, China. Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Li Ka Shing Faculty of Medicine, The University of Hong Kong, China.National Institute of Biological Sciences, Zhongguancun Life Science Park, Changping, Beijing, China.State Key Laboratory of Emerging Infectious Diseases The University of Hong Kong, China. Department of Microbiology The University of Hong Kong, China. Carol Yu Centre for Infection The University of Hong Kong, China. Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Li Ka Shing Faculty of Medicine, The University of Hong Kong, China.State Key Laboratory of Emerging Infectious Diseases The University of Hong Kong, China. Department of Microbiology The University of Hong Kong, China. Carol Yu Centre for Infection The University of Hong Kong, China. Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Li Ka Shing Faculty of Medicine, The University of Hong Kong, China.

Pub Type(s)

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

Language

eng

PubMed ID

29346682

Citation

Lau, Susanna K P., et al. "Receptor Usage of a Novel Bat Lineage C Betacoronavirus Reveals Evolution of Middle East Respiratory Syndrome-Related Coronavirus Spike Proteins for Human Dipeptidyl Peptidase 4 Binding." The Journal of Infectious Diseases, vol. 218, no. 2, 2018, pp. 197-207.
Lau SKP, Zhang L, Luk HKH, et al. Receptor Usage of a Novel Bat Lineage C Betacoronavirus Reveals Evolution of Middle East Respiratory Syndrome-Related Coronavirus Spike Proteins for Human Dipeptidyl Peptidase 4 Binding. J Infect Dis. 2018;218(2):197-207.
Lau, S. K. P., Zhang, L., Luk, H. K. H., Xiong, L., Peng, X., Li, K. S. M., He, X., Zhao, P. S., Fan, R. Y. Y., Wong, A. C. P., Ahmed, S. S., Cai, J. P., Chan, J. F. W., Sun, Y., Jin, D., Chen, H., Lau, T. C. K., Kok, R. K. H., Li, W., ... Woo, P. C. Y. (2018). Receptor Usage of a Novel Bat Lineage C Betacoronavirus Reveals Evolution of Middle East Respiratory Syndrome-Related Coronavirus Spike Proteins for Human Dipeptidyl Peptidase 4 Binding. The Journal of Infectious Diseases, 218(2), 197-207. https://doi.org/10.1093/infdis/jiy018
Lau SKP, et al. Receptor Usage of a Novel Bat Lineage C Betacoronavirus Reveals Evolution of Middle East Respiratory Syndrome-Related Coronavirus Spike Proteins for Human Dipeptidyl Peptidase 4 Binding. J Infect Dis. 2018 06 20;218(2):197-207. PubMed PMID: 29346682.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Receptor Usage of a Novel Bat Lineage C Betacoronavirus Reveals Evolution of Middle East Respiratory Syndrome-Related Coronavirus Spike Proteins for Human Dipeptidyl Peptidase 4 Binding. AU - Lau,Susanna K P, AU - Zhang,Libiao, AU - Luk,Hayes K H, AU - Xiong,Lifeng, AU - Peng,Xingwen, AU - Li,Kenneth S M, AU - He,Xiangyang, AU - Zhao,Pyrear Su-Hui, AU - Fan,Rachel Y Y, AU - Wong,Antonio C P, AU - Ahmed,Syed Shakeel, AU - Cai,Jian-Piao, AU - Chan,Jasper F W, AU - Sun,Yinyan, AU - Jin,Dongyan, AU - Chen,Honglin, AU - Lau,Terrence C K, AU - Kok,Raven K H, AU - Li,Wenhui, AU - Yuen,Kwok-Yung, AU - Woo,Patrick C Y, PY - 2017/11/20/received PY - 2018/01/15/accepted PY - 2018/1/19/pubmed PY - 2019/9/13/medline PY - 2018/1/19/entrez SP - 197 EP - 207 JF - The Journal of infectious diseases JO - J Infect Dis VL - 218 IS - 2 N2 - Although bats are known to harbor Middle East Respiratory Syndrome coronavirus (MERS-CoV)-related viruses, the role of bats in the evolutionary origin and pathway remains obscure. We identified a novel MERS-CoV-related betacoronavirus, Hp-BatCoV HKU25, from Chinese pipistrelle bats. Although it is closely related to MERS-CoV in most genome regions, its spike protein occupies a phylogenetic position between that of Ty-BatCoV HKU4 and Pi-BatCoV HKU5. Because Ty-BatCoV HKU4 but not Pi-BatCoV HKU5 can use the MERS-CoV receptor human dipeptidyl peptidase 4 (hDPP4) for cell entry, we tested the ability of Hp-BatCoV HKU25 to bind and use hDPP4. The HKU25-receptor binding domain (RBD) can bind to hDPP4 protein and hDPP4-expressing cells, but it does so with lower efficiency than that of MERS-RBD. Pseudovirus assays showed that HKU25-spike can use hDPP4 for entry to hDPP4-expressing cells, although with lower efficiency than that of MERS-spike and HKU4-spike. Our findings support a bat origin of MERS-CoV and suggest that bat CoV spike proteins may have evolved in a stepwise manner for binding to hDPP4. SN - 1537-6613 UR - https://www.unboundmedicine.com/medline/citation/29346682/Receptor_Usage_of_a_Novel_Bat_Lineage_C_Betacoronavirus_Reveals_Evolution_of_Middle_East_Respiratory_Syndrome_Related_Coronavirus_Spike_Proteins_for_Human_Dipeptidyl_Peptidase_4_Binding_ L2 - https://academic.oup.com/jid/article-lookup/doi/10.1093/infdis/jiy018 DB - PRIME DP - Unbound Medicine ER -