Infection with MERS-CoV Causes Lethal Pneumonia in the Common Marmoset
Identifieur interne : 001C35 ( Main/Merge ); précédent : 001C34; suivant : 001C36Infection with MERS-CoV Causes Lethal Pneumonia in the Common Marmoset
Auteurs : Darryl Falzarano [États-Unis] ; Emmie De Wit [États-Unis] ; Friederike Feldmann [États-Unis] ; Angela L. Rasmussen [États-Unis] ; Atsushi Okumura [États-Unis] ; Xinxia Peng [États-Unis] ; Matthew J. Thomas [États-Unis] ; Neeltje Van Doremalen [États-Unis] ; Elaine Haddock [États-Unis] ; Lee Nagy [États-Unis] ; Rachel Lacasse [États-Unis] ; Tingting Liu [États-Unis] ; Jiang Zhu [États-Unis] ; Jason S. Mclellan [États-Unis] ; Dana P. Scott [États-Unis] ; Michael G. Katze [États-Unis] ; Heinz Feldmann [États-Unis, Canada] ; Vincent J. Munster [États-Unis]Source :
- PLoS Pathogens [ 1553-7366 ] ; 2014.
Descripteurs français
- KwdFr :
- Animaux, Callithrix, Coronavirus du syndrome respiratoire du Moyen-Orient, Immunohistochimie, Infections à coronavirus (anatomopathologie), Infections à coronavirus (virologie), Modèles animaux de maladie humaine, Mâle, Pneumopathie virale (anatomopathologie), Pneumopathie virale (virologie), Réaction de polymérisation en chaine en temps réel.
- MESH :
- anatomopathologie : Infections à coronavirus, Pneumopathie virale.
- virologie : Infections à coronavirus, Pneumopathie virale.
- Animaux, Callithrix, Coronavirus du syndrome respiratoire du Moyen-Orient, Immunohistochimie, Modèles animaux de maladie humaine, Mâle, Réaction de polymérisation en chaine en temps réel.
English descriptors
- KwdEn :
- MESH :
Abstract
The availability of a robust disease model is essential for the development of countermeasures for Middle East respiratory syndrome coronavirus (MERS-CoV). While a rhesus macaque model of MERS-CoV has been established, the lack of uniform, severe disease in this model complicates the analysis of countermeasure studies. Modeling of the interaction between the MERS-CoV spike glycoprotein and its receptor dipeptidyl peptidase 4 predicted comparable interaction energies in common marmosets and humans. The suitability of the marmoset as a MERS-CoV model was tested by inoculation via combined intratracheal, intranasal, oral and ocular routes. Most of the marmosets developed a progressive severe pneumonia leading to euthanasia of some animals. Extensive lesions were evident in the lungs of all animals necropsied at different time points post inoculation. Some animals were also viremic; high viral loads were detected in the lungs of all infected animals, and total RNAseq demonstrated the induction of immune and inflammatory pathways. This is the first description of a severe, partially lethal, disease model of MERS-CoV, and as such will have a major impact on the ability to assess the efficacy of vaccines and treatment strategies as well as allowing more detailed pathogenesis studies.
Url:
DOI: 10.1371/journal.ppat.1004250
PubMed: 25144235
PubMed Central: 4140844
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PMC:4140844Le document en format XML
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<affiliation wicri:level="2"><nlm:aff id="aff1"><addr-line>Disease Modeling and Transmission, Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rocky Mountain Laboratories, Hamilton, Montana, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Disease Modeling and Transmission, Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rocky Mountain Laboratories, Hamilton, Montana</wicri:regionArea>
<placeName><region type="state">Montana</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Nagy, Lee" sort="Nagy, Lee" uniqKey="Nagy L" first="Lee" last="Nagy">Lee Nagy</name>
<affiliation wicri:level="2"><nlm:aff id="aff2"><addr-line>Rocky Mountain Veterinary Branch, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rocky Mountain Laboratories, Hamilton, Montana, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Rocky Mountain Veterinary Branch, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rocky Mountain Laboratories, Hamilton, Montana</wicri:regionArea>
<placeName><region type="state">Montana</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Lacasse, Rachel" sort="Lacasse, Rachel" uniqKey="Lacasse R" first="Rachel" last="Lacasse">Rachel Lacasse</name>
<affiliation wicri:level="2"><nlm:aff id="aff2"><addr-line>Rocky Mountain Veterinary Branch, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rocky Mountain Laboratories, Hamilton, Montana, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Rocky Mountain Veterinary Branch, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rocky Mountain Laboratories, Hamilton, Montana</wicri:regionArea>
<placeName><region type="state">Montana</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Liu, Tingting" sort="Liu, Tingting" uniqKey="Liu T" first="Tingting" last="Liu">Tingting Liu</name>
<affiliation wicri:level="2"><nlm:aff id="aff5"><addr-line>Department of Immunology and Microbial Science, Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, California, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Immunology and Microbial Science, Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, California</wicri:regionArea>
<placeName><region type="state">Californie</region>
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</affiliation>
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<affiliation wicri:level="2"><nlm:aff id="aff5"><addr-line>Department of Immunology and Microbial Science, Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, California, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Immunology and Microbial Science, Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, California</wicri:regionArea>
<placeName><region type="state">Californie</region>
</placeName>
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<affiliation wicri:level="2"><nlm:aff id="aff6"><addr-line>Department of Biochemistry, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Biochemistry, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire</wicri:regionArea>
<placeName><region type="state">New Hampshire</region>
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<affiliation wicri:level="2"><nlm:aff id="aff2"><addr-line>Rocky Mountain Veterinary Branch, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rocky Mountain Laboratories, Hamilton, Montana, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Rocky Mountain Veterinary Branch, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rocky Mountain Laboratories, Hamilton, Montana</wicri:regionArea>
<placeName><region type="state">Montana</region>
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<author><name sortKey="Katze, Michael G" sort="Katze, Michael G" uniqKey="Katze M" first="Michael G." last="Katze">Michael G. Katze</name>
<affiliation wicri:level="4"><nlm:aff id="aff3"><addr-line>Department of Microbiology, University of Washington, Seattle, Washington, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Microbiology, University of Washington, Seattle, Washington</wicri:regionArea>
<placeName><region type="state">Washington (État)</region>
<settlement type="city">Seattle</settlement>
</placeName>
<orgName type="university">Université de Washington</orgName>
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<author><name sortKey="Feldmann, Heinz" sort="Feldmann, Heinz" uniqKey="Feldmann H" first="Heinz" last="Feldmann">Heinz Feldmann</name>
<affiliation wicri:level="2"><nlm:aff id="aff1"><addr-line>Disease Modeling and Transmission, Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rocky Mountain Laboratories, Hamilton, Montana, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Disease Modeling and Transmission, Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rocky Mountain Laboratories, Hamilton, Montana</wicri:regionArea>
<placeName><region type="state">Montana</region>
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</affiliation>
<affiliation wicri:level="4"><nlm:aff id="aff7"><addr-line>Department of Medical Microbiology, University of Manitoba, Winnipeg, Manitoba, Canada</addr-line>
</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea>Department of Medical Microbiology, University of Manitoba, Winnipeg, Manitoba</wicri:regionArea>
<orgName type="university">Université du Manitoba</orgName>
<placeName><settlement type="city">Winnipeg</settlement>
<region type="state">Manitoba</region>
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<author><name sortKey="Munster, Vincent J" sort="Munster, Vincent J" uniqKey="Munster V" first="Vincent J." last="Munster">Vincent J. Munster</name>
<affiliation wicri:level="2"><nlm:aff id="aff4"><addr-line>Virus Ecology Unit, Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rocky Mountain Laboratories, Hamilton, Montana, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Virus Ecology Unit, Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rocky Mountain Laboratories, Hamilton, Montana</wicri:regionArea>
<placeName><region type="state">Montana</region>
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<series><title level="j">PLoS Pathogens</title>
<idno type="ISSN">1553-7366</idno>
<idno type="eISSN">1553-7374</idno>
<imprint><date when="2014">2014</date>
</imprint>
</series>
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<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term>
<term>Callithrix</term>
<term>Coronavirus Infections (pathology)</term>
<term>Coronavirus Infections (virology)</term>
<term>Disease Models, Animal</term>
<term>Immunohistochemistry</term>
<term>Male</term>
<term>Middle East Respiratory Syndrome Coronavirus</term>
<term>Pneumonia, Viral (pathology)</term>
<term>Pneumonia, Viral (virology)</term>
<term>Real-Time Polymerase Chain Reaction</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>Animaux</term>
<term>Callithrix</term>
<term>Coronavirus du syndrome respiratoire du Moyen-Orient</term>
<term>Immunohistochimie</term>
<term>Infections à coronavirus (anatomopathologie)</term>
<term>Infections à coronavirus (virologie)</term>
<term>Modèles animaux de maladie humaine</term>
<term>Mâle</term>
<term>Pneumopathie virale (anatomopathologie)</term>
<term>Pneumopathie virale (virologie)</term>
<term>Réaction de polymérisation en chaine en temps réel</term>
</keywords>
<keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr"><term>Infections à coronavirus</term>
<term>Pneumopathie virale</term>
</keywords>
<keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Coronavirus Infections</term>
<term>Pneumonia, Viral</term>
</keywords>
<keywords scheme="MESH" qualifier="virologie" xml:lang="fr"><term>Infections à coronavirus</term>
<term>Pneumopathie virale</term>
</keywords>
<keywords scheme="MESH" qualifier="virology" xml:lang="en"><term>Coronavirus Infections</term>
<term>Pneumonia, Viral</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Animals</term>
<term>Callithrix</term>
<term>Disease Models, Animal</term>
<term>Immunohistochemistry</term>
<term>Male</term>
<term>Middle East Respiratory Syndrome Coronavirus</term>
<term>Real-Time Polymerase Chain Reaction</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr"><term>Animaux</term>
<term>Callithrix</term>
<term>Coronavirus du syndrome respiratoire du Moyen-Orient</term>
<term>Immunohistochimie</term>
<term>Modèles animaux de maladie humaine</term>
<term>Mâle</term>
<term>Réaction de polymérisation en chaine en temps réel</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en"><p>The availability of a robust disease model is essential for the development of countermeasures for Middle East respiratory syndrome coronavirus (MERS-CoV). While a rhesus macaque model of MERS-CoV has been established, the lack of uniform, severe disease in this model complicates the analysis of countermeasure studies. Modeling of the interaction between the MERS-CoV spike glycoprotein and its receptor dipeptidyl peptidase 4 predicted comparable interaction energies in common marmosets and humans. The suitability of the marmoset as a MERS-CoV model was tested by inoculation via combined intratracheal, intranasal, oral and ocular routes. Most of the marmosets developed a progressive severe pneumonia leading to euthanasia of some animals. Extensive lesions were evident in the lungs of all animals necropsied at different time points post inoculation. Some animals were also viremic; high viral loads were detected in the lungs of all infected animals, and total RNAseq demonstrated the induction of immune and inflammatory pathways. This is the first description of a severe, partially lethal, disease model of MERS-CoV, and as such will have a major impact on the ability to assess the efficacy of vaccines and treatment strategies as well as allowing more detailed pathogenesis studies.</p>
</div>
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