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
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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.
Dipeptidyl Peptidase 4, Hypsugo Bat, Middle East Respiratory Syndrome Coronavirus, Spike Glycoprotein
The Journal of Infectious Diseases, Vol. 218, no. 2 (2018-07-15).
Lau, Susanna K. P.; Zhang, Libiao; Luk, Hayes, K. H.; Xiong, Lifeng; Peng, Xingwen; Li, Kenneth S. M.; He, Xiangyang; Zhao, Pyrear Su-Hei; Fan, Rachel, Y. Y.; Wong, Antonio C. P.; Ahmed, Syed Shakeel; Cai, Jian-Piao; Chan, Jasper F. W.; Sun, Yinyan; Jin, Dongyan; Chen, Honglin; Lau, Terrence C. K.; Kok, Raven, K. H.; Li, Wenhui; Yuen, Kwok-Yung; and Woo, Patrick C. Y., "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" (2018). KIP Articles. 4972.