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Proc Natl Acad Sci USA. Middle East respiratory syndrome coronavirus (MERS-CoV) causes transient lower respiratory tract infection in rhesus macaques

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  • Proc Natl Acad Sci USA. Middle East respiratory syndrome coronavirus (MERS-CoV) causes transient lower respiratory tract infection in rhesus macaques

    [Source: Proceedings of the National Academy of Sciences of the United States of America, full page: (LINK). Abstract, edited.]

    Middle East respiratory syndrome coronavirus (MERS-CoV) causes transient lower respiratory tract infection in rhesus macaques

    Emmie de Wit<SUP>a</SUP>, Angela L. Rasmussen<SUP>b</SUP>, Darryl Falzarano<SUP>a</SUP>, Trenton Bushmaker<SUP>a</SUP>, Friederike Feldmann<SUP>c</SUP>, Douglas L. Brining<SUP>c</SUP>, Elizabeth R. Fischer<SUP>d</SUP>, Cynthia Martellaro<SUP>a</SUP>, Atsushi Okumura<SUP>b</SUP>, Jean Chang<SUP>b</SUP>, Dana Scott<SUP>c</SUP>, Arndt G. Benecke<SUP>b</SUP>,<SUP>e</SUP>, Michael G. Katze<SUP>b</SUP>, Heinz Feldmann<SUP>a</SUP>,<SUP>f</SUP>,<SUP>1</SUP>, and Vincent J. Munster<SUP>a</SUP>,<SUP>1</SUP>
    Author Affiliations: <SUP>a</SUP>Laboratory of Virology, <SUP>c</SUP>Rocky Mountain Veterinary Branch, and <SUP>d</SUP>Microscopy Unit, Research Technologies Branch, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840; <SUP>b</SUP>Department of Microbiology, University of Washington, Seattle, WA 98195; <SUP>e</SUP>Department of Biology, Universit? Pierre et Marie Curie, Centre National de la Recherche Scientific, Unit? Mixte de Recherche 7224, 75005 Paris, France; and <SUP>f</SUP>Department of Medical Microbiology, University of Manitoba, Winnipeg, MB, Canada R3E 0J9

    Edited* by Tilahun D. Yilma, University of California, Davis, CA, and approved August 26, 2013 (received for review June 6, 2013)


    The Middle East respiratory syndrome coronavirus (MERS-CoV) is the latest emerged coronavirus causing severe respiratory disease with a high case fatality rate in humans. To better understand the disease caused by MERS-CoV, we developed a rhesus macaque model. Infection of rhesus macaques with MERS-CoV resulted in the rapid development of a transient pneumonia, with MERS-CoV replication largely restricted to the lower respiratory tract. This affinity of MERS-CoV for the lungs partly explains the severity of the disease observed in humans. The MERS-CoV rhesus macaque model will be instrumental in developing and testing vaccine and treatment options for an emerging viral pathogen with pandemic potential.


    In 2012, a novel betacoronavirus, designated Middle East respiratory syndrome coronavirus or MERS-CoV and associated with severe respiratory disease in humans, emerged in the Arabian Peninsula. To date, 108 human cases have been reported, including cases of human-to-human transmission. The availability of an animal disease model is essential for understanding pathogenesis and developing effective countermeasures. Upon a combination of intratracheal, ocular, oral, and intranasal inoculation with 7 ? 10<SUP>6</SUP> 50% tissue culture infectious dose of the MERS-CoV isolate HCoV-EMC/2012, rhesus macaques developed a transient lower respiratory tract infection. Clinical signs, virus shedding, virus replication in respiratory tissues, gene expression, and cytokine and chemokine profiles peaked early in infection and decreased over time. MERS-CoV caused a multifocal, mild to marked interstitial pneumonia, with virus replication occurring mainly in alveolar pneumocytes. This tropism of MERS-CoV for the lower respiratory tract may explain the severity of the disease observed in humans and the, up to now, limited human-to-human transmission.

    emerging infectious disease ? DPP4


    <SUP>1</SUP>To whom correspondence may be addressed. E-mail: or

    Author contributions: E.d.W., H.F., and V.J.M. designed research; E.d.W., A.L.R., D.F., T.B., F.F., D.L.B., E.R.F., C.M., A.O., J.C., D.S., H.F., and V.J.M. performed research; E.d.W., A.L.R., D.F., E.R.F., A.O., D.S., A.G.B., M.G.K., H.F., and V.J.M. analyzed data; and E.d.W., A.L.R., H.F., and V.J.M. wrote the paper.

    The authors declare no conflict of interest.

    *This Direct Submission article had a prearranged editor.

    Data deposition: The data reported in this paper have been deposited in the Gene Expression Omnibus (GEO) database, (accession no. GSE44542) and are also available to the public at

    This article contains supporting information online at