Adaptive evolution of bat dipeptidyl peptidase 4 (dpp4): implications for the origin and emergence of Middle East respiratory syndrome coronavirus

Virol J. 2013 Oct 10:10:304. doi: 10.1186/1743-422X-10-304.

Abstract

Background: The newly emerged Middle East respiratory syndrome coronavirus (MERS-CoV) that first appeared in Saudi Arabia during the summer of 2012 has to date (20th September 2013) caused 58 human deaths. MERS-CoV utilizes the dipeptidyl peptidase 4 (DPP4) host cell receptor, and analysis of the long-term interaction between virus and receptor provides key information on the evolutionary events that lead to the viral emergence.

Findings: We show that bat DPP4 genes have been subject to significant adaptive evolution, suggestive of a long-term arms-race between bats and MERS related CoVs. In particular, we identify three positively selected residues in DPP4 that directly interact with the viral surface glycoprotein.

Conclusions: Our study suggests that the evolutionary lineage leading to MERS-CoV may have circulated in bats for a substantial time period.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chiroptera
  • Cluster Analysis
  • Coronavirus / physiology*
  • Dipeptidyl Peptidase 4 / genetics*
  • Dipeptidyl Peptidase 4 / metabolism*
  • Evolution, Molecular*
  • Phylogeny
  • Protein Binding
  • Protein Interaction Mapping
  • Receptors, Virus / genetics*
  • Receptors, Virus / metabolism*
  • Selection, Genetic
  • Sequence Analysis, DNA
  • Viral Envelope Proteins / metabolism
  • Virus Attachment*

Substances

  • Receptors, Virus
  • Viral Envelope Proteins
  • Dipeptidyl Peptidase 4