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Analysis: Nature - Receptor for NCoV Found

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  • Analysis: Nature - Receptor for NCoV Found

    hat tip Michael Coston

    Wednesday, March 13, 2013

    Nature: Receptor For NCoV Found

    Photo Credit NIAID

    # 7004

    A fairly technical report appears in the Journal Nature today - produced by research teams in both Europe and Saudi Arabia - that establishes the mechanism by which the novel Coronavirus NCoV (here called hCoV-EMC) binds to, and infects, mammalian cells.

    They found this novel coronavirus uses a well known cell surface protein called dipeptidyl peptidase 4 (DPP4) to enter and infect human cells.
    This DPP4 cell surface protein (also called CD26) is evolutionarily conserved in other species, including bats (suspected of being potential species), non-human primates, and other animals ? all of which suggests that this virus might be able to infect a wide range of hosts.
    Working in vitro with Vero & COS-7 cells (African Green Monkey kidneys), Huh-7 (human hepato-carcinoma) and kidney cells of the P. pipistrellus bat, researchers found how hCoV-EMC?s receptor-binding domain latched onto cells.
    Using protein-specific antibodies, they were able to block specific receptors, systematically narrowing the field of possible attachment sites.
    When DPP4 proteins were blocked, the virus was no longer able to attach to cells and cause infection. A discovery that could potentially lead to some specific treatment for this virus down the line.
    These are, of course, early days. And we still know very little about the origin ? and the potential ? of this virus.
    The researchers point out that (in humans) DPP4 is primarily expressed by epithelial cells in the in kidney, small intestine, liver and prostate. They also observed that DPP4 is expressed by non-ciliated bronchial epithelial cells of the upper airway.
    Locations consistent with the clinical picture of infection we?ve seen over the past year, that has often included both pneumonia and renal failure.
    Declan Butler at Nature has far more on all of this, after which you?ll find a link to the study.
    Receptor for new coronavirus found

    Virus might have many animal reservoirs.
    Declan Butler 13 March 2013

    And the study?s abstract can be found at:
    Dipeptidyl peptidase 4 is a functional receptor for the emerging human coronavirus-EMC

    V. Stalin Raj, Huihui Mou, Saskia L. Smits, Dick H. W. Dekkers, Marcel A. M?ller, Ronald Dijkman, Doreen Muth, Jeroen A. A. Demmers, Ali Zaki, Ron A. M. Fouchier, Volker Thiel, Christian Drosten, Peter J. M. Rottier, Albert D. M. E. Osterhaus, Berend Jan Bosch & Bart L. Haagmans
    Posted by Michael Coston at <a class="timestamp-link" href="" rel="bookmark" title="permanent link"><abbr class="published" title="2013-03-13T14:32:00-04:00">2:32 PM</abbr>

  • #2
    Re: Analysis: Nature - Receptor for NCoV Found

    [Source: Nature, full text: (LINK). Abstract, edited.]
    Nature | Letter

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

    V. Stalin Raj,<SUP>1, 9 </SUP>Huihui Mou,<SUP>2, 9 </SUP>Saskia L. Smits,<SUP>1, 3 </SUP>Dick H. W. Dekkers,<SUP>4 </SUP>Marcel A. M?ller,<SUP>5 </SUP>Ronald Dijkman,<SUP>6 </SUP>Doreen Muth,<SUP>5 </SUP>Jeroen A. A. Demmers,<SUP>4 </SUP>Ali Zaki,<SUP>7 </SUP>Ron A. M. Fouchier,<SUP>1 </SUP>Volker Thiel,<SUP>6 8 </SUP>Christian Drosten,<SUP>5 </SUP>Peter J. M. Rottier,<SUP>2 </SUP>Albert D. M. E. Osterhaus,<SUP>1 </SUP>Berend Jan Bosch<SUP>2 </SUP>& Bart L. Haagmans<SUP>1</SUP>
    Journal name: Nature - Volume: 495, Pages: 251?254 - Date published: (14 March 2013)

    DOI: doi:10.1038/nature12005

    Received 03 December 2012 - Accepted 13 February 2013 - Published online 13 March 2013

    Most human coronaviruses cause mild upper respiratory tract disease but may be associated with more severe pulmonary disease in immunocompromised individuals<SUP>1</SUP>. However, SARS coronavirus caused severe lower respiratory disease with nearly 10% mortality and evidence of systemic spread<SUP>2</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>3, 4</SUP>. Viral genome analysis revealed close relatedness to coronaviruses found in bats<SUP>5</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 (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.

    Subject terms: Viral pathogenesis

    Affiliations: Department of Viroscience, Erasmus Medical Center, 3000 CA Rotterdam, The Netherlands (V. Stalin Raj, Saskia L. Smits, Ron A. M. Fouchier, Albert D. M. E. Osterhaus & Bart L. Haagmans); Virology Division, Department of Infectious Diseases & Immunology, Faculty of Veterinary Medicine, Utrecht University, 3508 TD Utrecht, the Netherlands (Huihui Mou, Peter J. M. Rottier & Berend Jan Bosch); Viroclinics Biosciences BV, 3029 AK Rotterdam, The Netherlands (Saskia L. Smits); Proteomics Department, Erasmus Medical Center, 3000 CA Rotterdam, The Netherlands (Dick H. W. Dekkers & Jeroen A. A. Demmers); Institute of Virology, University of Bonn Medical Centre, 53105 Bonn, Germany (Marcel A. M?ller, Doreen Muth & Christian Drosten); Institute of Immunobiology, Kantonal Hospital St Gallen, 9007 St Gallen, Switzerland (Ronald Dijkman & Volker Thiel); Virology Laboratory, Dr Soliman Fakeeh Hospital, Jeddah, Saudi Arabia (Ali Zaki); Vetsuisse Faculty, University of Z?rich, 8057 Z?rich, Switzerland (Volker Thiel)

    Contributions: B.J.B., V.S.R. and B.L.H. designed and coordinated the study. B.J.B. and B.L.H. contributed equally to the study. V.S.R., H.M., S.L.S., D.H.W.D., M.A.M., R.D., D.M., B.J.B. and B.L.H conducted the experiments. A.Z. provided the virus, and R.A.M.F., J.A.A.D., V.T., C.D., A.D.M.E.O. and P.J.M.R. supervised part of the experiments. All authors contributed to the interpretations and conclusions presented. B.J.B. and B.L.H. wrote the manuscript, and A.D.M.E.O. and P.J.M.R. participated in editing it.

    Competing financial interests: V.S.R., B.J.B., R.A.M.F., A.D.M.E.O. and B.L.H. are inventors on a patent application related to this work.

    The P. pipistrellus bat DPP4 sequence has been deposited in GenBank/EMBL/DDBJ under accession number KC249974.