Coronavirus Host Range Expansion and Middle East Respiratory Syndrome Coronavirus Emergence: Biochemical Mechanisms and Evolutionary Perspectives

Annu Rev Virol. 2015 Nov;2(1):95-117. doi: 10.1146/annurev-virology-100114-055029. Epub 2015 Aug 7.


Coronaviruses have frequently expanded their host range in recent history, with two events resulting in severe disease outbreaks in human populations. Severe acute respiratory syndrome coronavirus (SARS-CoV) emerged in 2003 in Southeast Asia and rapidly spread around the world before it was controlled by public health intervention strategies. The 2012 Middle East respiratory syndrome coronavirus (MERS-CoV) outbreak represents another prime example of virus emergence from a zoonotic reservoir. Here, we review the current knowledge of coronavirus cross-species transmission, with particular focus on MERS-CoV. MERS-CoV is still circulating in the human population, and the mechanisms governing its cross-species transmission have been only partially elucidated, highlighting a need for further investigation. We discuss biochemical determinants mediating MERS-CoV host cell permissivity, including virus spike interactions with the MERS-CoV cell surface receptor dipeptidyl peptidase 4 (DPP4), and evolutionary mechanisms that may facilitate host range expansion, including recombination, mutator alleles, and mutational robustness. Understanding these mechanisms can help us better recognize the threat of emergence for currently circulating zoonotic strains.

Keywords: emergence; host cell receptor; mutational robustness; mutator alleles; recombination; virus evolution.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Animals
  • Coronavirus Infections / enzymology
  • Coronavirus Infections / genetics
  • Coronavirus Infections / virology*
  • Dipeptidyl Peptidase 4 / genetics
  • Dipeptidyl Peptidase 4 / metabolism
  • Evolution, Molecular*
  • Host Specificity*
  • Humans
  • Middle East Respiratory Syndrome Coronavirus / classification
  • Middle East Respiratory Syndrome Coronavirus / genetics
  • Middle East Respiratory Syndrome Coronavirus / isolation & purification
  • Middle East Respiratory Syndrome Coronavirus / physiology*
  • Receptors, Virus / genetics
  • Receptors, Virus / metabolism


  • Receptors, Virus
  • Dipeptidyl Peptidase 4