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- Title
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.
- Authors
Lau, Susanna K. P.; Libiao Zhang; Luk, Hayes K. H.; Lifeng Xiong; Xingwen Peng; Li, Kenneth S. M.; Xiangyang He; Pyrear Su-Hui Zhao; Fan, Rachel Y. Y.; Wong, Antonio C. P.; Ahmed, Syed Shakeel; Jian-Piao Cai; Chan, Jasper F. W.; Yinyan Sun; Dongyan Jin; Honglin Chen; Lau, Terrence C. K.; Kok, Raven K. H.; Wenhui Li; Kwok-Yung Yuen
- 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.
- Subjects
MIDDLE East respiratory syndrome; CORONAVIRUS diseases; CD26 antigen; BINDING site assay; PROTEIN binding; BETACORONAVIRUS
- Publication
Journal of Infectious Diseases, 2018, Vol 218, Issue 2, p197
- ISSN
0022-1899
- Publication type
journal article
- DOI
10.1093/infdis/jiy018