A spike-modified Middle East respiratory syndrome coronavirus (MERS-CoV) infectious clone elicits mild respiratory disease in infected rhesus macaques
Identifieur interne : 000A80 ( Main/Exploration ); précédent : 000A79; suivant : 000A81A spike-modified Middle East respiratory syndrome coronavirus (MERS-CoV) infectious clone elicits mild respiratory disease in infected rhesus macaques
Auteurs : Adam S. Cockrell [États-Unis] ; Joshua C. Johnson [États-Unis] ; Ian N. Moore [États-Unis] ; David X. Liu [États-Unis] ; Kevin W. Bock [États-Unis] ; Madeline G. Douglas [États-Unis] ; Rachel L. Graham [États-Unis] ; Jeffrey Solomon [États-Unis] ; Lisa Torzewski [États-Unis] ; Christopher Bartos [États-Unis] ; Randy Hart [États-Unis] ; Ralph S. Baric [États-Unis] ; Reed F. Johnson [États-Unis]Source :
- Scientific Reports [ 2045-2322 ] ; 2018.
Descripteurs français
- KwdFr :
- ARN viral (isolement et purification), Animaux, Charge virale (génétique), Coronavirus du syndrome respiratoire du Moyen-Orient (génétique), Coronavirus du syndrome respiratoire du Moyen-Orient (isolement et purification), Coronavirus du syndrome respiratoire du Moyen-Orient (pathogénicité), Coronavirus du syndrome respiratoire du Moyen-Orient (physiologie), Humains, Indice de gravité médicale, Infections à coronavirus (anatomopathologie), Infections à coronavirus (diagnostic), Infections à coronavirus (virologie), Macaca mulatta, Modèles animaux de maladie humaine, Poumon (anatomopathologie), Poumon (imagerie diagnostique), Poumon (virologie), Réplication virale (génétique), Tomodensitométrie, Traitement d'image par ordinateur.
- MESH :
- anatomopathologie : Infections à coronavirus, Poumon.
- diagnostic : Infections à coronavirus.
- génétique : Charge virale, Coronavirus du syndrome respiratoire du Moyen-Orient, Réplication virale.
- imagerie diagnostique : Poumon.
- isolement et purification : ARN viral, Coronavirus du syndrome respiratoire du Moyen-Orient.
- pathogénicité : Coronavirus du syndrome respiratoire du Moyen-Orient.
- physiologie : Coronavirus du syndrome respiratoire du Moyen-Orient.
- virologie : Infections à coronavirus, Poumon.
- Animaux, Humains, Indice de gravité médicale, Macaca mulatta, Modèles animaux de maladie humaine, Tomodensitométrie, Traitement d'image par ordinateur.
English descriptors
- KwdEn :
- Animals, Coronavirus Infections (diagnosis), Coronavirus Infections (pathology), Coronavirus Infections (virology), Disease Models, Animal, Humans, Image Processing, Computer-Assisted, Lung (diagnostic imaging), Lung (pathology), Lung (virology), Macaca mulatta, Middle East Respiratory Syndrome Coronavirus (genetics), Middle East Respiratory Syndrome Coronavirus (isolation & purification), Middle East Respiratory Syndrome Coronavirus (pathogenicity), Middle East Respiratory Syndrome Coronavirus (physiology), RNA, Viral (isolation & purification), Severity of Illness Index, Tomography, X-Ray Computed, Viral Load (genetics), Virus Replication (genetics).
- MESH :
- chemical , isolation & purification : RNA, Viral.
- diagnosis : Coronavirus Infections.
- diagnostic imaging : Lung.
- genetics : Middle East Respiratory Syndrome Coronavirus, Viral Load, Virus Replication.
- isolation & purification : Middle East Respiratory Syndrome Coronavirus.
- pathogenicity : Middle East Respiratory Syndrome Coronavirus.
- pathology : Coronavirus Infections, Lung.
- physiology : Middle East Respiratory Syndrome Coronavirus.
- virology : Coronavirus Infections, Lung.
- Animals, Disease Models, Animal, Humans, Image Processing, Computer-Assisted, Macaca mulatta, Severity of Illness Index, Tomography, X-Ray Computed.
Abstract
The recurrence of new human cases of Middle East respiratory syndrome coronavirus (MERS-CoV) underscores the need for effective therapeutic countermeasures. Nonhuman primate models are considered the gold standard for preclinical evaluation of therapeutic countermeasures. However, MERS-CoV-induced severe respiratory disease in humans is associated with high viral loads in the lower respiratory tract, which may be difficult to achieve in nonhuman primate models. Considering this limitation, we wanted to ascertain the effectiveness of using a MERS-CoV infectious clone (icMERS-0) previously shown to replicate to higher titers than the wild-type EMC 2012 strain. We observed respiratory disease resulting from exposure to the icMERS-0 strain as measured by CT in rhesus monkeys with concomitant detection of virus antigen by immunohistochemistry. Overall, respiratory disease was mild and transient, resolving by day 30 post-infection. Although pulmonary disease was mild, these results demonstrate for the first time the utility of CT imaging to measure disease elicited by a MERS-CoV infectious clone system in nonhuman primate models.
Url:
DOI: 10.1038/s41598-018-28900-1
PubMed: 30013082
PubMed Central: 6048037
Affiliations:
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Le document en format XML
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">A spike-modified Middle East respiratory syndrome coronavirus (MERS-CoV) infectious clone elicits mild respiratory disease in infected rhesus macaques</title>
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Frederick, Maryland 21702 USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Maryland</region>
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<author><name sortKey="Hart, Randy" sort="Hart, Randy" uniqKey="Hart R" first="Randy" last="Hart">Randy Hart</name>
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Frederick, Maryland 21702 USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Maryland</region>
</placeName>
<wicri:cityArea>Frederick</wicri:cityArea>
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<author><name sortKey="Baric, Ralph S" sort="Baric, Ralph S" uniqKey="Baric R" first="Ralph S." last="Baric">Ralph S. Baric</name>
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<institution-id institution-id-type="GRID">grid.10698.36</institution-id>
<institution>Department of Epidemiology,</institution>
<institution>University of North Carolina-Chapel Hill, Chapel Hill,</institution>
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North Carolina, 27599 USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>North Carolina</wicri:regionArea>
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<author><name sortKey="Johnson, Reed F" sort="Johnson, Reed F" uniqKey="Johnson R" first="Reed F." last="Johnson">Reed F. Johnson</name>
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<institution-id institution-id-type="GRID">grid.419681.3</institution-id>
<institution>Emerging Viral Pathogens Section,</institution>
<institution>Laboratory of Immunoregulation, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 8200 Research Plaza,</institution>
</institution-wrap>
Frederick, Maryland 21702 USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Maryland</region>
</placeName>
<wicri:cityArea>Frederick</wicri:cityArea>
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</analytic>
<series><title level="j">Scientific Reports</title>
<idno type="eISSN">2045-2322</idno>
<imprint><date when="2018">2018</date>
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<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term>
<term>Coronavirus Infections (diagnosis)</term>
<term>Coronavirus Infections (pathology)</term>
<term>Coronavirus Infections (virology)</term>
<term>Disease Models, Animal</term>
<term>Humans</term>
<term>Image Processing, Computer-Assisted</term>
<term>Lung (diagnostic imaging)</term>
<term>Lung (pathology)</term>
<term>Lung (virology)</term>
<term>Macaca mulatta</term>
<term>Middle East Respiratory Syndrome Coronavirus (genetics)</term>
<term>Middle East Respiratory Syndrome Coronavirus (isolation & purification)</term>
<term>Middle East Respiratory Syndrome Coronavirus (pathogenicity)</term>
<term>Middle East Respiratory Syndrome Coronavirus (physiology)</term>
<term>RNA, Viral (isolation & purification)</term>
<term>Severity of Illness Index</term>
<term>Tomography, X-Ray Computed</term>
<term>Viral Load (genetics)</term>
<term>Virus Replication (genetics)</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>ARN viral (isolement et purification)</term>
<term>Animaux</term>
<term>Charge virale (génétique)</term>
<term>Coronavirus du syndrome respiratoire du Moyen-Orient (génétique)</term>
<term>Coronavirus du syndrome respiratoire du Moyen-Orient (isolement et purification)</term>
<term>Coronavirus du syndrome respiratoire du Moyen-Orient (pathogénicité)</term>
<term>Coronavirus du syndrome respiratoire du Moyen-Orient (physiologie)</term>
<term>Humains</term>
<term>Indice de gravité médicale</term>
<term>Infections à coronavirus (anatomopathologie)</term>
<term>Infections à coronavirus (diagnostic)</term>
<term>Infections à coronavirus (virologie)</term>
<term>Macaca mulatta</term>
<term>Modèles animaux de maladie humaine</term>
<term>Poumon (anatomopathologie)</term>
<term>Poumon (imagerie diagnostique)</term>
<term>Poumon (virologie)</term>
<term>Réplication virale (génétique)</term>
<term>Tomodensitométrie</term>
<term>Traitement d'image par ordinateur</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="isolation & purification" xml:lang="en"><term>RNA, Viral</term>
</keywords>
<keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr"><term>Infections à coronavirus</term>
<term>Poumon</term>
</keywords>
<keywords scheme="MESH" qualifier="diagnosis" xml:lang="en"><term>Coronavirus Infections</term>
</keywords>
<keywords scheme="MESH" qualifier="diagnostic" xml:lang="fr"><term>Infections à coronavirus</term>
</keywords>
<keywords scheme="MESH" qualifier="diagnostic imaging" xml:lang="en"><term>Lung</term>
</keywords>
<keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Middle East Respiratory Syndrome Coronavirus</term>
<term>Viral Load</term>
<term>Virus Replication</term>
</keywords>
<keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Charge virale</term>
<term>Coronavirus du syndrome respiratoire du Moyen-Orient</term>
<term>Réplication virale</term>
</keywords>
<keywords scheme="MESH" qualifier="imagerie diagnostique" xml:lang="fr"><term>Poumon</term>
</keywords>
<keywords scheme="MESH" qualifier="isolation & purification" xml:lang="en"><term>Middle East Respiratory Syndrome Coronavirus</term>
</keywords>
<keywords scheme="MESH" qualifier="isolement et purification" xml:lang="fr"><term>ARN viral</term>
<term>Coronavirus du syndrome respiratoire du Moyen-Orient</term>
</keywords>
<keywords scheme="MESH" qualifier="pathogenicity" xml:lang="en"><term>Middle East Respiratory Syndrome Coronavirus</term>
</keywords>
<keywords scheme="MESH" qualifier="pathogénicité" xml:lang="fr"><term>Coronavirus du syndrome respiratoire du Moyen-Orient</term>
</keywords>
<keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Coronavirus Infections</term>
<term>Lung</term>
</keywords>
<keywords scheme="MESH" qualifier="physiologie" xml:lang="fr"><term>Coronavirus du syndrome respiratoire du Moyen-Orient</term>
</keywords>
<keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>Middle East Respiratory Syndrome Coronavirus</term>
</keywords>
<keywords scheme="MESH" qualifier="virologie" xml:lang="fr"><term>Infections à coronavirus</term>
<term>Poumon</term>
</keywords>
<keywords scheme="MESH" qualifier="virology" xml:lang="en"><term>Coronavirus Infections</term>
<term>Lung</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Animals</term>
<term>Disease Models, Animal</term>
<term>Humans</term>
<term>Image Processing, Computer-Assisted</term>
<term>Macaca mulatta</term>
<term>Severity of Illness Index</term>
<term>Tomography, X-Ray Computed</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr"><term>Animaux</term>
<term>Humains</term>
<term>Indice de gravité médicale</term>
<term>Macaca mulatta</term>
<term>Modèles animaux de maladie humaine</term>
<term>Tomodensitométrie</term>
<term>Traitement d'image par ordinateur</term>
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<front><div type="abstract" xml:lang="en"><p id="Par1">The recurrence of new human cases of Middle East respiratory syndrome coronavirus (MERS-CoV) underscores the need for effective therapeutic countermeasures. Nonhuman primate models are considered the gold standard for preclinical evaluation of therapeutic countermeasures. However, MERS-CoV-induced severe respiratory disease in humans is associated with high viral loads in the lower respiratory tract, which may be difficult to achieve in nonhuman primate models. Considering this limitation, we wanted to ascertain the effectiveness of using a MERS-CoV infectious clone (icMERS-0) previously shown to replicate to higher titers than the wild-type EMC 2012 strain. We observed respiratory disease resulting from exposure to the icMERS-0 strain as measured by CT in rhesus monkeys with concomitant detection of virus antigen by immunohistochemistry. Overall, respiratory disease was mild and transient, resolving by day 30 post-infection. Although pulmonary disease was mild, these results demonstrate for the first time the utility of CT imaging to measure disease elicited by a MERS-CoV infectious clone system in nonhuman primate models.</p>
</div>
</front>
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<biblStruct><analytic><author><name sortKey="Cockrell, As" uniqKey="Cockrell A">AS Cockrell</name>
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</listBibl>
</div1>
</back>
</TEI>
<affiliations><list><country><li>États-Unis</li>
</country>
<region><li>Maryland</li>
</region>
</list>
<tree><country name="États-Unis"><noRegion><name sortKey="Cockrell, Adam S" sort="Cockrell, Adam S" uniqKey="Cockrell A" first="Adam S." last="Cockrell">Adam S. Cockrell</name>
</noRegion>
<name sortKey="Baric, Ralph S" sort="Baric, Ralph S" uniqKey="Baric R" first="Ralph S." last="Baric">Ralph S. Baric</name>
<name sortKey="Bartos, Christopher" sort="Bartos, Christopher" uniqKey="Bartos C" first="Christopher" last="Bartos">Christopher Bartos</name>
<name sortKey="Bock, Kevin W" sort="Bock, Kevin W" uniqKey="Bock K" first="Kevin W." last="Bock">Kevin W. Bock</name>
<name sortKey="Douglas, Madeline G" sort="Douglas, Madeline G" uniqKey="Douglas M" first="Madeline G." last="Douglas">Madeline G. Douglas</name>
<name sortKey="Graham, Rachel L" sort="Graham, Rachel L" uniqKey="Graham R" first="Rachel L." last="Graham">Rachel L. Graham</name>
<name sortKey="Hart, Randy" sort="Hart, Randy" uniqKey="Hart R" first="Randy" last="Hart">Randy Hart</name>
<name sortKey="Johnson, Joshua C" sort="Johnson, Joshua C" uniqKey="Johnson J" first="Joshua C." last="Johnson">Joshua C. Johnson</name>
<name sortKey="Johnson, Reed F" sort="Johnson, Reed F" uniqKey="Johnson R" first="Reed F." last="Johnson">Reed F. Johnson</name>
<name sortKey="Liu, David X" sort="Liu, David X" uniqKey="Liu D" first="David X." last="Liu">David X. Liu</name>
<name sortKey="Moore, Ian N" sort="Moore, Ian N" uniqKey="Moore I" first="Ian N." last="Moore">Ian N. Moore</name>
<name sortKey="Solomon, Jeffrey" sort="Solomon, Jeffrey" uniqKey="Solomon J" first="Jeffrey" last="Solomon">Jeffrey Solomon</name>
<name sortKey="Torzewski, Lisa" sort="Torzewski, Lisa" uniqKey="Torzewski L" first="Lisa" last="Torzewski">Lisa Torzewski</name>
</country>
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