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

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journalpeer-review

32 Scopus Citations
View graph of relations

Author(s)

  • Susanna K. P. Lau
  • Libiao Zhang
  • Hayes K. H. Luk
  • Lifeng Xiong
  • Xingwen Peng
  • Kenneth S. M. Li
  • Xiangyang He
  • Pyrear Su-Hui Zhao
  • Rachel Y. Y. Fan
  • Antonio C. P. Wong
  • Syed Shakeel Ahmed
  • Jian-Piao Cai
  • Jasper F. W. Chan
  • Yinyan Sun
  • Dongyan Jin
  • Honglin Chen
  • Raven K. H. Kok
  • Wenhui Li
  • Kwok-Yung Yuen
  • Patrick C. Y. Woo

Related Research Unit(s)

Detail(s)

Original languageEnglish
Pages (from-to)197-207
Journal / PublicationJournal of Infectious Diseases
Volume218
Issue number2
Online published16 Jan 2018
Publication statusPublished - 15 Jul 2018

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.

Research Area(s)

  • dipeptidyl peptidase 4, Hypsugo bat, Middle East Respiratory Syndrome coronavirus, spike glycoprotein

Citation Format(s)

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. / 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.

In: Journal of Infectious Diseases, Vol. 218, No. 2, 15.07.2018, p. 197-207.

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journalpeer-review