Dipeptidyl peptidase 4 is a functional receptor for the emerging human coronavirus-EMC
Identifieur interne : 000450 ( Pmc/Curation ); précédent : 000449; suivant : 000451Dipeptidyl peptidase 4 is a functional receptor for the emerging human coronavirus-EMC
Auteurs : V. Stalin Raj ; Huihui Mou ; Saskia L. Smits [Pays-Bas] ; Dick H. W. Dekkers ; Marcel A. Müller ; Ronald Dijkman ; Doreen Muth ; Jeroen A. A. Demmers ; Ali Zaki [Arabie saoudite] ; Ron A. M. Fouchier ; Volker Thiel ; Christian Drosten ; Peter J. M. Rottier ; Albert D. M. E. Osterhaus ; Berend Jan Bosch ; Bart L. HaagmansSource :
- Nature [ 0028-0836 ] ; 2013.
Abstract
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.
The online version of this article (doi:10.1038/nature12005) contains supplementary material, which is available to authorized users.
Url:
DOI: 10.1038/nature12005
PubMed: 23486063
PubMed Central: 7095326
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Haagmans</name><affiliation><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="GRID">grid.5645.2</institution-id><institution-id institution-id-type="ISNI">000000040459992X</institution-id><institution>Department of Viroscience,</institution><institution>Erasmus Medical Center, 3000 CA Rotterdam, The Netherlands,</institution></institution-wrap>,</nlm:aff></affiliation></author></analytic><series><title level="j">Nature</title><idno type="ISSN">0028-0836</idno><idno type="eISSN">1476-4687</idno><imprint><date when="2013">2013</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p id="Par1">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.</p><sec><title>Supplementary information</title><p>The online version of this article (doi:10.1038/nature12005) contains supplementary material, which is available to authorized users.</p></sec></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Weiss, Sr" uniqKey="Weiss S">SR Weiss</name></author><author><name sortKey="Navas Martin, S" uniqKey="Navas Martin S">S Navas-Martin</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Peiris, Jsm" uniqKey="Peiris J">JSM Peiris</name></author><author><name sortKey="Guan, Y" uniqKey="Guan Y">Y Guan</name></author><author><name sortKey="Yuen, Ky" uniqKey="Yuen K">KY Yuen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zaki, Am" uniqKey="Zaki A">AM Zaki</name></author><author><name sortKey="Van Boheemen, S" uniqKey="Van Boheemen S">S van Boheemen</name></author><author><name sortKey="Bestebroer, Tm" uniqKey="Bestebroer T">TM Bestebroer</name></author><author><name sortKey="Osterhaus, Ad" 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<front><journal-meta><journal-id journal-id-type="nlm-ta">Nature</journal-id><journal-id journal-id-type="iso-abbrev">Nature</journal-id><journal-title-group><journal-title>Nature</journal-title></journal-title-group><issn pub-type="ppub">0028-0836</issn><issn pub-type="epub">1476-4687</issn><publisher><publisher-name>Nature Publishing Group UK</publisher-name><publisher-loc>London</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">23486063</article-id><article-id pub-id-type="pmc">7095326</article-id><article-id pub-id-type="publisher-id">BFnature12005</article-id><article-id pub-id-type="doi">10.1038/nature12005</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>Dipeptidyl peptidase 4 is a functional receptor for the emerging human coronavirus-EMC</article-title></title-group><contrib-group><contrib contrib-type="author" equal-contrib="yes"><name><surname>Raj</surname><given-names>V. Stalin</given-names></name><xref ref-type="aff" rid="Aff1">1</xref></contrib><contrib contrib-type="author" equal-contrib="yes"><name><surname>Mou</surname><given-names>Huihui</given-names></name><xref ref-type="aff" rid="Aff2">2</xref></contrib><contrib contrib-type="author"><name><surname>Smits</surname><given-names>Saskia L.</given-names></name><xref ref-type="aff" rid="Aff1">1</xref><xref ref-type="aff" rid="Aff3">3</xref></contrib><contrib contrib-type="author"><name><surname>Dekkers</surname><given-names>Dick H. W.</given-names></name><xref ref-type="aff" rid="Aff4">4</xref></contrib><contrib contrib-type="author"><name><surname>Müller</surname><given-names>Marcel A.</given-names></name><xref ref-type="aff" rid="Aff5">5</xref></contrib><contrib contrib-type="author"><name><surname>Dijkman</surname><given-names>Ronald</given-names></name><xref ref-type="aff" rid="Aff6">6</xref></contrib><contrib contrib-type="author"><name><surname>Muth</surname><given-names>Doreen</given-names></name><xref ref-type="aff" rid="Aff5">5</xref></contrib><contrib contrib-type="author"><name><surname>Demmers</surname><given-names>Jeroen A. A.</given-names></name><xref ref-type="aff" rid="Aff4">4</xref></contrib><contrib contrib-type="author"><name><surname>Zaki</surname><given-names>Ali</given-names></name><xref ref-type="aff" rid="Aff7">7</xref></contrib><contrib contrib-type="author"><name><surname>Fouchier</surname><given-names>Ron A. M.</given-names></name><xref ref-type="aff" rid="Aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Thiel</surname><given-names>Volker</given-names></name><xref ref-type="aff" rid="Aff6">6</xref><xref ref-type="aff" rid="Aff8">8</xref></contrib><contrib contrib-type="author"><name><surname>Drosten</surname><given-names>Christian</given-names></name><xref ref-type="aff" rid="Aff5">5</xref></contrib><contrib contrib-type="author"><name><surname>Rottier</surname><given-names>Peter J. M.</given-names></name><xref ref-type="aff" rid="Aff2">2</xref></contrib><contrib contrib-type="author"><name><surname>Osterhaus</surname><given-names>Albert D. M. E.</given-names></name><xref ref-type="aff" rid="Aff1">1</xref></contrib><contrib contrib-type="author" corresp="yes"><name><surname>Bosch</surname><given-names>Berend Jan</given-names></name><address><email>b.j.bosch@uu.nl</email></address><xref ref-type="aff" rid="Aff2">2</xref></contrib><contrib contrib-type="author" corresp="yes"><name><surname>Haagmans</surname><given-names>Bart L.</given-names></name><address><email>b.haagmans@erasmusmc.nl</email></address><xref ref-type="aff" rid="Aff1">1</xref></contrib><aff id="Aff1"><label>1</label><institution-wrap><institution-id institution-id-type="GRID">grid.5645.2</institution-id><institution-id institution-id-type="ISNI">000000040459992X</institution-id><institution>Department of Viroscience,</institution><institution>Erasmus Medical Center, 3000 CA Rotterdam, The Netherlands,</institution></institution-wrap>,</aff><aff id="Aff2"><label>2</label><institution-wrap><institution-id institution-id-type="GRID">grid.5477.1</institution-id><institution-id institution-id-type="ISNI">0000000120346234</institution-id><institution>Virology Division, Department of Infectious Diseases & Immunology,</institution><institution>Faculty of Veterinary Medicine, Utrecht University, 3508 TD Utrecht, the Netherlands,</institution></institution-wrap>,</aff><aff id="Aff3"><label>3</label>Viroclinics Biosciences BV, 3029 AK Rotterdam, The Netherlands, ,</aff><aff id="Aff4"><label>4</label><institution-wrap><institution-id institution-id-type="GRID">grid.5645.2</institution-id><institution-id institution-id-type="ISNI">000000040459992X</institution-id><institution>Proteomics Department,</institution><institution>Erasmus Medical Center, 3000 CA Rotterdam, The Netherlands,</institution></institution-wrap>,</aff><aff id="Aff5"><label>5</label><institution-wrap><institution-id institution-id-type="GRID">grid.15090.3d</institution-id><institution-id institution-id-type="ISNI">0000 0000 8786 803X</institution-id><institution>Institute of Virology, University of Bonn Medical Centre, 53105 Bonn, Germany,</institution></institution-wrap>,</aff><aff id="Aff6"><label>6</label><institution-wrap><institution-id institution-id-type="GRID">grid.413349.8</institution-id><institution-id institution-id-type="ISNI">0000 0001 2294 4705</institution-id><institution>Institute of Immunobiology, Kantonal Hospital St Gallen, 9007 St Gallen, Switzerland,</institution></institution-wrap>,</aff><aff id="Aff7"><label>7</label><institution-wrap><institution-id institution-id-type="GRID">grid.416111.2</institution-id><institution-id institution-id-type="ISNI">0000 0004 1790 6466</institution-id><institution>Virology Laboratory, Dr Soliman Fakeeh Hospital,</institution></institution-wrap>Jeddah, Saudi Arabia</aff><aff id="Aff8"><label>8</label><institution-wrap><institution-id institution-id-type="GRID">grid.7400.3</institution-id><institution-id institution-id-type="ISNI">0000 0004 1937 0650</institution-id><institution>Vetsuisse Faculty, University of Zürich, 8057 Zürich, Switzerland,</institution></institution-wrap>,</aff></contrib-group><pub-date pub-type="epub"><day>13</day><month>3</month><year>2013</year></pub-date><pub-date pub-type="ppub"><year>2013</year></pub-date><volume>495</volume><issue>7440</issue><fpage>251</fpage><lpage>254</lpage><history><date date-type="received"><day>3</day><month>12</month><year>2012</year></date><date date-type="accepted"><day>13</day><month>2</month><year>2013</year></date></history><permissions><copyright-statement>© Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. 2013</copyright-statement><license><license-p>This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.</license-p></license></permissions><abstract id="Abs1" abstract-type="web-summary"><p id="Par1">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.</p><sec><title>Supplementary information</title><p>The online version of this article (doi:10.1038/nature12005) contains supplementary material, which is available to authorized users.</p></sec></abstract><abstract id="Abs2" abstract-type="LongSummary"><title>Human receptor for emerging coronavirus</title><p id="Par2">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.</p><sec><title>Supplementary information</title><p>The online version of this article (doi:10.1038/nature12005) contains supplementary material, which is available to authorized users.</p></sec></abstract><abstract id="Abs3"><p id="Par3">Most human coronaviruses cause mild upper respiratory tract disease but may be associated with more severe pulmonary disease in immunocompromised individuals<sup><xref ref-type="bibr" rid="CR1">1</xref></sup>. However, SARS coronavirus caused severe lower respiratory disease with nearly 10% mortality and evidence of systemic spread<sup><xref ref-type="bibr" rid="CR2">2</xref></sup>. Recently, another coronavirus (human coronavirus-Erasmus Medical Center (hCoV-EMC)) was identified in patients with severe and sometimes lethal lower respiratory tract infection<sup><xref ref-type="bibr" rid="CR3">3</xref>,<xref ref-type="bibr" rid="CR4">4</xref></sup>. Viral genome analysis revealed close relatedness to coronaviruses found in bats<sup><xref ref-type="bibr" rid="CR5">5</xref></sup>. 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 (<italic>Pipistrellus pipistrellus</italic>) 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.</p><sec><title>Supplementary information</title><p>The online version of this article (doi:10.1038/nature12005) contains supplementary material, which is available to authorized users.</p></sec></abstract><kwd-group kwd-group-type="npg-subject"><title>Subject terms</title><kwd>Viral pathogenesis</kwd></kwd-group><custom-meta-group><custom-meta><meta-name>issue-copyright-statement</meta-name><meta-value>© Springer Nature Limited 2013</meta-value></custom-meta></custom-meta-group></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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