Dipeptidyl peptidase 4 is a functional receptor for the emerging human coronavirus-EMC

• Published in: Nature (London) Vol. 495; no. 7440; pp. 251 - 254
• Main Authors: Raj, V. Stalin, Mou, Huihui, Smits, Saskia L., Dekkers, Dick H. W., Müller, Marcel A., Dijkman, Ronald, Muth, Doreen, Demmers, Jeroen A. A., Zaki, Ali, Fouchier, Ron A. M., Thiel, Volker, Drosten, Christian, Rottier, Peter J. M., Osterhaus, Albert D. M. E., Bosch, Berend Jan, Haagmans, Bart L.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 14.03.2013; Nature Publishing Group
• Subjects: 631/326/596/2555; Animals; Bronchioles - cytology; Causes of; Chiroptera; Chlorocebus aethiops; Complications and side effects; Coronavirus - classification; Coronavirus - metabolism; Coronavirus infections; Coronavirus Infections - epidemiology; Coronavirus Infections - genetics; Coronavirus Infections - metabolism; Coronavirus Infections - virology; Coronaviruses; COS Cells; COVID-19; Diagnosis; Dipeptidyl Peptidase 4 - genetics; Dipeptidyl Peptidase 4 - metabolism; Distribution; Epidemiology; Epithelial Cells - virology; Genetic aspects; Host Specificity; Humanities and Social Sciences; Humans; Infections; letter; Medical research; Medicine, Experimental; Molecular Sequence Data; multidisciplinary; Pathogenesis; Patient outcomes; Physiological aspects; Proteases; Proteins; Receptors, Virus - genetics; Receptors, Virus - metabolism; Respiratory diseases; Respiratory tract; Science; Studies; Ubiquitin-proteasome system; Zoonoses; Netherlands; United States
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/nature12005

Human coronavirus-EMC (hCoV-EMC) is a new coronavirus that has killed around half of the few humans infected so far; this study now identifies DPP4 as the receptor that this virus uses to infect cells. Human receptor for emerging coronavirus The emerging pathogenic coronavirus hCoV-EMC, first identified in September 2012, has been fatal in about half of the few humans infected so far. Bart Haagmans and colleagues have now identified the receptor that this virus uses to infect cells. In contrast to the related virus SARS-CoV, which uses angiotensin converting enzyme 2, the functional receptor for hCoV-EMC is dipeptidyl peptidase 4 (DPP4, also known as CD26), an exopeptidase found on non-ciliated cells in the lower respiratory tract. This enzyme is highly conserved across different species, and hCoV-EMC can also use bat DPP4 as a functional receptor — a possible clue as to the host range and epidemiological history of this new virus. The findings may also be important for the development of intervention strategies. Most human coronaviruses cause mild upper respiratory tract disease but may be associated with more severe pulmonary disease in immunocompromised individuals 1 . However, SARS coronavirus caused severe lower respiratory disease with nearly 10% mortality and evidence of systemic spread 2 . Recently, another coronavirus (human coronavirus-Erasmus Medical Center (hCoV-EMC)) was identified in patients with severe and sometimes lethal lower respiratory tract infection 3 , 4 . Viral genome analysis revealed close relatedness to coronaviruses found in bats 5 . 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.