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Dipeptidyl peptidase 4 is a functional receptor for the emerging human coronavirus-EMC.
Nature. 2013 Mar 14; 495(7440):251-4.Nat

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+Show Affiliations

Department of Viroscience, Erasmus Medical Center, 3000 CA Rotterdam, The Netherlands.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23486063

Citation

Raj, V Stalin, et al. "Dipeptidyl Peptidase 4 Is a Functional Receptor for the Emerging Human Coronavirus-EMC." Nature, vol. 495, no. 7440, 2013, pp. 251-4.
Raj VS, Mou H, Smits SL, et al. Dipeptidyl peptidase 4 is a functional receptor for the emerging human coronavirus-EMC. Nature. 2013;495(7440):251-4.
Raj, V. S., Mou, H., Smits, S. L., Dekkers, D. H., Müller, M. A., Dijkman, R., Muth, D., Demmers, J. A., Zaki, A., Fouchier, R. A., Thiel, V., Drosten, C., Rottier, P. J., Osterhaus, A. D., Bosch, B. J., & Haagmans, B. L. (2013). Dipeptidyl peptidase 4 is a functional receptor for the emerging human coronavirus-EMC. Nature, 495(7440), 251-4. https://doi.org/10.1038/nature12005
Raj VS, et al. Dipeptidyl Peptidase 4 Is a Functional Receptor for the Emerging Human Coronavirus-EMC. Nature. 2013 Mar 14;495(7440):251-4. PubMed PMID: 23486063.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Dipeptidyl peptidase 4 is a functional receptor for the emerging human coronavirus-EMC. AU - Raj,V Stalin, AU - Mou,Huihui, AU - Smits,Saskia L, AU - Dekkers,Dick H W, AU - Müller,Marcel A, AU - Dijkman,Ronald, AU - Muth,Doreen, AU - Demmers,Jeroen A A, AU - Zaki,Ali, AU - Fouchier,Ron A M, AU - Thiel,Volker, AU - Drosten,Christian, AU - Rottier,Peter J M, AU - Osterhaus,Albert D M E, AU - Bosch,Berend Jan, AU - Haagmans,Bart L, PY - 2012/12/03/received PY - 2013/02/13/accepted PY - 2013/3/15/entrez PY - 2013/3/15/pubmed PY - 2013/4/16/medline SP - 251 EP - 4 JF - Nature JO - Nature VL - 495 IS - 7440 N2 - 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. SN - 1476-4687 UR - https://www.unboundmedicine.com/medline/citation/23486063/Dipeptidyl_peptidase_4_is_a_functional_receptor_for_the_emerging_human_coronavirus_EMC_ L2 - https://doi.org/10.1038/nature12005 DB - PRIME DP - Unbound Medicine ER -