Receptor usage of a novel bat lineage C betacoronavirus reveals evolution of Middle East respiratory syndrome-related coronavirus spike proteins for human …

SKP Lau, L Zhang, HKH Luk, L Xiong… - The Journal of …, 2018 - academic.oup.com
SKP Lau, L Zhang, HKH Luk, L Xiong, X Peng, KSM Li, X He, PSH Zhao, RYY Fan…
The Journal of infectious diseases, 2018academic.oup.com
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 …
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.
Oxford University Press