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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>
<SUP></SUP>
<SUP></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)
Significance
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.
Abstract
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
Footnotes
<SUP>1</SUP>To whom correspondence may be addressed. E-mail: feldmannh@niaid.nih.gov or Vincent.Munster@nih.gov.
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, www.ncbi.nlm.nih.gov/geo (accession no. GSE44542) and are also available to the public at http://viromics.washington.edu.
This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1310744110/-/DCSupplemental.
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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>
<SUP></SUP>
<SUP></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)
Significance
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.
Abstract
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
Footnotes
<SUP>1</SUP>To whom correspondence may be addressed. E-mail: feldmannh@niaid.nih.gov or Vincent.Munster@nih.gov.
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, www.ncbi.nlm.nih.gov/geo (accession no. GSE44542) and are also available to the public at http://viromics.washington.edu.
This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1310744110/-/DCSupplemental.
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