[Source: Nature, full text: (LINK). Abstract, edited.]
Nature | Letter
Dipeptidyl peptidase 4 is a functional receptor for the emerging human coronavirus-EMC
V. Stalin Raj,1, 9 Huihui Mou,2, 9 Saskia L. Smits,1, 3 Dick H. W. Dekkers,4 Marcel A. Müller,5 Ronald Dijkman,6 Doreen Muth,5 Jeroen A. A. Demmers,4 Ali Zaki,7 Ron A. M. Fouchier,1 Volker Thiel,6 8 Christian Drosten,5 Peter J. M. Rottier,2 Albert D. M. E. Osterhaus,1 Berend Jan Bosch2 & Bart L. Haagmans1
Journal name: Nature - Volume: 495, Pages: 251–254 - Date published: (14 March 2013)
Received 03 December 2012 - Accepted 13 February 2013 - Published online 13 March 2013
Most human coronaviruses cause mild upper respiratory tract disease but may be associated with more severe pulmonary disease in immunocompromised individuals1. However, SARS coronavirus caused severe lower respiratory disease with nearly 10% mortality and evidence of systemic spread2. Recently, another coronavirus (human coronavirus-Erasmus Medical Center (hCoV-EMC)) was identified in patients with severe and sometimes lethal lower respiratory tract infection3, 4. Viral genome analysis revealed close relatedness to coronaviruses found in bats5. Here we identify dipeptidyl peptidase 4 (DPP4; also known as CD26) as a functional receptor for hCoV-EMC. DPP4 specifically co-purified with the receptor-binding S1 domain of the hCoV-EMC spike protein from lysates of susceptible Huh-7 cells. Antibodies directed against DPP4 inhibited hCoV-EMC infection of primary human bronchial epithelial cells and Huh-7 cells. Expression of human and bat (Pipistrellus pipistrellus) DPP4 in non-susceptible COS-7 cells enabled infection by hCoV-EMC. The use of the evolutionarily conserved DPP4 protein from different species as a functional receptor provides clues about the host range potential of hCoV-EMC. In addition, it will contribute critically to our understanding of the pathogenesis and epidemiology of this emerging human coronavirus, and may facilitate the development of intervention strategies.
Subject terms: Viral pathogenesis
Affiliations: Department of Viroscience, Erasmus Medical Center, 3000 CA Rotterdam, The Netherlands (V. Stalin Raj, Saskia L. Smits, Ron A. M. Fouchier, Albert D. M. E. Osterhaus & Bart L. Haagmans); Virology Division, Department of Infectious Diseases & Immunology, Faculty of Veterinary Medicine, Utrecht University, 3508 TD Utrecht, the Netherlands (Huihui Mou, Peter J. M. Rottier & Berend Jan Bosch); Viroclinics Biosciences BV, 3029 AK Rotterdam, The Netherlands (Saskia L. Smits); Proteomics Department, Erasmus Medical Center, 3000 CA Rotterdam, The Netherlands (Dick H. W. Dekkers & Jeroen A. A. Demmers); Institute of Virology, University of Bonn Medical Centre, 53105 Bonn, Germany (Marcel A. Müller, Doreen Muth & Christian Drosten); Institute of Immunobiology, Kantonal Hospital St Gallen, 9007 St Gallen, Switzerland (Ronald Dijkman & Volker Thiel); Virology Laboratory, Dr Soliman Fakeeh Hospital, Jeddah, Saudi Arabia (Ali Zaki); Vetsuisse Faculty, University of Zürich, 8057 Zürich, Switzerland (Volker Thiel)
Contributions: B.J.B., V.S.R. and B.L.H. designed and coordinated the study. B.J.B. and B.L.H. contributed equally to the study. V.S.R., H.M., S.L.S., D.H.W.D., M.A.M., R.D., D.M., B.J.B. and B.L.H conducted the experiments. A.Z. provided the virus, and R.A.M.F., J.A.A.D., V.T., C.D., A.D.M.E.O. and P.J.M.R. supervised part of the experiments. All authors contributed to the interpretations and conclusions presented. B.J.B. and B.L.H. wrote the manuscript, and A.D.M.E.O. and P.J.M.R. participated in editing it.
Competing financial interests: V.S.R., B.J.B., R.A.M.F., A.D.M.E.O. and B.L.H. are inventors on a patent application related to this work.
The P. pipistrellus bat DPP4 sequence has been deposited in GenBank/EMBL/DDBJ under accession number KC249974.