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

作者：Susanna K. P. Lau, Libiao Zhang, Hayes K. H. Luk, Lifeng Xiong, Xingwen Peng, Kenneth S. M. Li, Xiangyang He, Suhui Zhao, Rachel Y. Y. Fan, Antonio C. P. Wong, Syed Shakeel Ahmed, Jian‐Piao Cai, Jasper Fuk‐Woo Chan, Yinyan Sun, Dong‐Yan Jin, Honglin Chen, Terrence Chi‐Kong Lau, Raven K. H. Kok, Wenhui Li, Kwok‐Yung Yuen, Patrick C. Y. Woo · 发表于：The Journal of Infectious Diseases · 年份：2018 · DOI：10.1093/infdis/jiy018 · 被引用次数：112 · 研究领域：SARS-CoV-2 and COVID-19 Research、Animal Virus Infections Studies、Viral gastroenteritis research and epidemiology

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.