title: Dipeptidyl peptidase 4 is a functional receptor for the emerging human coronavirus-EMC.
abstract: Most human coronaviruses cause mild upper respiratory tract disease but may be associated with more severe pulmonary disease in immunocompromised individuals. However, SARS coronavirus caused severe lower respiratory disease with nearly 10% mortality and evidence of systemic spread. Recently, another coronavirus (human coronavirus-Erasmus Medical Center (hCoV-EMC)) was identified in patients with severe and sometimes lethal lower respiratory tract infection. Viral genome analysis revealed close relatedness to coronaviruses found in bats. 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.
authors.affiliation: Department of Viroscience, Erasmus Medical Center, 3000 CA Rotterdam, The Netherlands.
authors.forename: V Stalin
authors.initials: VS
authors.lastname: Raj
authors.forename: Huihui
authors.initials: H
authors.lastname: Mou
authors.forename: Saskia L
authors.initials: SL
authors.lastname: Smits
authors.forename: Dick H W
authors.initials: DH
authors.lastname: Dekkers
authors.forename: Marcel A
authors.initials: MA
authors.lastname: Müller
authors.forename: Ronald
authors.initials: R
authors.lastname: Dijkman
authors.forename: Doreen
authors.initials: D
authors.lastname: Muth
authors.forename: Jeroen A A
authors.initials: JA
authors.lastname: Demmers
authors.forename: Ali
authors.initials: A
authors.lastname: Zaki
authors.forename: Ron A M
authors.initials: RA
authors.lastname: Fouchier
authors.forename: Volker
authors.initials: V
authors.lastname: Thiel
authors.forename: Christian
authors.initials: C
authors.lastname: Drosten
authors.forename: Peter J M
authors.initials: PJ
authors.lastname: Rottier
authors.forename: Albert D M E
authors.initials: AD
authors.lastname: Osterhaus
authors.forename: Berend Jan
authors.initials: BJ
authors.lastname: Bosch
authors.forename: Bart L
authors.initials: BL
authors.lastname: Haagmans
mesh_terms: D000818:Animals; D055745:Bronchioles / Q000166:cytology; D019556:COS Cells; D002685:Chiroptera; D002522:Chlorocebus aethiops; D017934:Coronavirus / Q000145:classification* / Q000378:metabolism*; D018352:Coronavirus Infections / Q000453:epidemiology / Q000235:genetics / Q000378:metabolism / Q000821:virology; D018819:Dipeptidyl Peptidase 4 / Q000235:genetics / Q000378:metabolism*; D004847:Epithelial Cells / Q000821:virology; D058507:Host Specificity; D006801:Humans; D008969:Molecular Sequence Data; D011991:Receptors, Virus / Q000235:genetics / Q000378:metabolism*
chemical_list: D011991:Receptors, Virus; C042807:DPP4 protein, human; D018819:Dipeptidyl Peptidase 4