Mapping the Specific Amino Acid Residues That Make Hamster DPP4 Functional as a Receptor for Middle East Respiratory Syndrome Coronavirus

J Virol. 2016 May 12;90(11):5499-5502. doi: 10.1128/JVI.03267-15. Print 2016 Jun 1.

Abstract

The novel emerging coronavirus Middle East respiratory syndrome coronavirus (MERS-CoV) binds to its receptor, dipeptidyl peptidase 4 (DPP4), via 14 interacting amino acids. We previously showed that if the five interacting amino acids which differ between hamster and human DPP4 are changed to the residues found in human DPP4, hamster DPP4 does act as a receptor. Here, we show that the functionality of hamster DPP4 as a receptor is severely decreased if less than 4 out of 5 amino acids are changed.

Importance: The novel emerging coronavirus MERS-CoV has infected >1,600 people worldwide, and the case fatality rate is ∼36%. In this study, we show that by changing 4 amino acids in hamster DPP4, this protein functions as a receptor for MERS-CoV. This work is vital in the development of new small-animal models, which will broaden our understanding of MERS-CoV and be instrumental in the development of countermeasures.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Amino Acids / chemistry*
  • Amino Acids / metabolism
  • Animals
  • Coronavirus Infections / virology
  • Cricetinae
  • Dipeptidyl Peptidase 4 / chemistry*
  • Dipeptidyl Peptidase 4 / metabolism*
  • Disease Models, Animal
  • Humans
  • Middle East Respiratory Syndrome Coronavirus / genetics
  • Middle East Respiratory Syndrome Coronavirus / metabolism*
  • Middle East Respiratory Syndrome Coronavirus / physiology
  • Models, Molecular
  • Protein Binding
  • Receptors, Virus / chemistry*
  • Receptors, Virus / metabolism
  • Virus Internalization
  • Virus Replication

Substances

  • Amino Acids
  • Receptors, Virus
  • DPP4 protein, human
  • Dipeptidyl Peptidase 4

Grants and funding

This research was supported by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH).