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

J Infect Dis. 2018 Jun 20;218(2):197-207. doi: 10.1093/infdis/jiy018.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Betacoronavirus / classification
  • Betacoronavirus / genetics
  • Betacoronavirus / isolation & purification
  • Betacoronavirus / physiology*
  • Chiroptera*
  • Dipeptidyl Peptidase 4 / metabolism*
  • Evolution, Molecular*
  • HEK293 Cells
  • Humans
  • Phylogeny
  • Protein Binding
  • Receptors, Virus / metabolism*
  • Sequence Analysis, DNA
  • Spike Glycoprotein, Coronavirus / genetics
  • Spike Glycoprotein, Coronavirus / metabolism*
  • Virus Internalization*

Substances

  • Receptors, Virus
  • Spike Glycoprotein, Coronavirus
  • DPP4 protein, human
  • Dipeptidyl Peptidase 4