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
Creators
- Lau, Susanna K. P.
- Zhang, Libiao
- Luk, Hayes K. H.
- Xiong, Lifeng
- Peng, Xingwen
- Li, Kenneth S. M.
- He, Xiangyang
- Zhao, Pyrear Su-Hui
- 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
- Woo, Patrick C. Y.
Contributors
Data curator:
Description
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.
Files
JInfectDis.218.2.197-207.pdf
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(8.2 MB)
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