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

By V. S. Raj, H. Mou, S. Smits, D. Dekkers, M. Müller, R. Dijkman, D. Muth, Jeroen A. A. Demmers, A. Zaki, R. Fouchier and 6 more. 2013

1,966 citations recorded by the source corpus.

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.

Subfields: Infectious Diseases, Oncology

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Citations in the corpus

A Universal Design of Betacoronavirus Vaccines against COVID-19, MERS, and SARS (2020, neutral): “, 2020c), whereas, MERSCoV uses human CD26 (also known as human dipeptidyl peptidase 4, hDPP4) (Lu et al., 2013; Raj et al., 2013).”
Title: Mosaic nanoparticles elicit cross-reactive immune responses to zoonotic coronaviruses in mice (2020, neutral): “The RBDs of human coronaviruses SARS-CoV-2, SARS-CoV, HCoV-NL63, and related animal coronaviruses (WIV1 and SCH014) use angiotensin-converting enzyme 2 (ACE2) as their host receptor (1, 8, 9), while other coronaviruses use receptors such as dipeptidyl peptidase 4 (10) or sialic acids (11, 12).”
COVID-19 infection: Origin, transmission, and characteristics of human coronaviruses (2020, positive): “The receptor-binding domain (RBD) is loosely attached among virus, therefore, the virus may infect multiple hosts [26,27].”
SARS and MERS: recent insights into emerging coronaviruses (2016, positive): “The envelope spike glycoprotein binds to its cellular receptor, angiotensin-converting enzyme 2 (ACE2) for SARS-CoV and dipeptidyl peptidase 4 (DPP4) for MERS-CoV 23 .”
SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor (2020, result): “In agreement with these findings, directed expression of human and bat (Rhinolophus alcyone) ACE2 but not human DPP4, the entry receptor used by MERS-CoV (Raj et al., 2013), or human APN, the entry receptor used by HCoV-229E (Yeager et al.”
Repurposing of Clinically Developed Drugs for Treatment of Middle East Respiratory Syndrome Coronavirus Infection (2014, background): “identified as the functional cellular receptor for MERS-CoV (4, 5).”
Middle East Respiratory Syndrome Coronavirus: Another Zoonotic Betacoronavirus Causing SARS-Like Disease (2015, background): “MERS-CoV is the first CoV that has been identified to use DPP4 as a functional receptor for entry into host cells (1, 46).”
Molecular Mechanism for Antibody-Dependent Enhancement of Coronavirus Entry (2019, background): “5 (ACE2) and dipeptidyl peptidase 4 (DPP4), respectively, as their viral receptor (26-28).”
Host cell proteases: critical determinants of coronavirus tropism and pathogenesis (2014, background): “Since its isolation and discovery in 2012, the complete viral genome was swiftly sequenced (van Boheemen et al., 2012), and its receptor, dipeptidyl peptidase 4 (DPP4 or CD26), rapidly identified (Raj et al., 2013).”
The COVID-19 Pandemic: A Comprehensive Review of Taxonomy, Genetics, Epidemiology, Diagnosis, Treatment, and Control (2020, background): “To gain access into the cell, MERS-CoV uses the human dipeptidyl peptidase 4 (DPP4) receptor [32].”
Structural insights into coronavirus entry (2019, background): “Many α-CoVs, including HCoV-229E, TGEV and PRCV, as well as porcine δ-CoV (PDCoV) utilize aminopeptidase N (APN) as entry receptor (Delmas et al., 1992; Delmas et al., 1993; Li et al., 2018; Reguera et al., 2012; Wong et al., 2017; Yeager et al., 1992) whereas MERS-CoV uses dipeptidyl peptidase 4 (D”
Prophylactic and postexposure efficacy of a potent human monoclonal antibody against MERS coronavirus (2015, positive): “The structure of the cellular receptor (CD26), which is conserved across many species (9), and the complex of CD26 with the receptor binding domain (RBD) of the S protein have been determined by X-ray crystallography (10, 11).”
Middle East respiratory syndrome coronavirus neutralising serum antibodies in dromedary camels: a comparative serological study (2013, background): “21 Data for exposure history of patients are scarce, but suggest contact with livestock, including dromedary camels and goats.”