An Acute Immune Response to Middle East Respiratory Syndrome Coronavirus Replication Contributes to Viral Pathogenicity
Identifieur interne : 001904 ( Main/Exploration ); précédent : 001903; suivant : 001905An Acute Immune Response to Middle East Respiratory Syndrome Coronavirus Replication Contributes to Viral Pathogenicity
Auteurs : Laura J. Baseler [États-Unis] ; Darryl Falzarano [États-Unis] ; Dana P. Scott [États-Unis] ; Rebecca Rosenke [États-Unis] ; Tina Thomas [États-Unis] ; Vincent J. Munster [États-Unis] ; Heinz Feldmann [États-Unis] ; Emmie De Wit [États-Unis]Source :
- The American Journal of Pathology [ 0002-9440 ] ; 2015.
Descripteurs français
- KwdFr :
- Animaux, Antigènes viraux (analyse), Antigènes viraux (sang), Callithrix, Charge virale, Coronavirus du syndrome respiratoire du Moyen-Orient (immunologie), Coronavirus du syndrome respiratoire du Moyen-Orient (pathogénicité), Coronavirus du syndrome respiratoire du Moyen-Orient (physiologie), Dipeptidyl peptidase 4 (métabolisme), Femelle, Granulocytes neutrophiles (immunologie), Humains, Infections à coronavirus (immunologie), Infections à coronavirus (virologie), Lapins, Macaca mulatta, Macrophages alvéolaires (), Modèles animaux de maladie humaine, Mâle, Pneumopathie virale (immunologie), Poumon (anatomopathologie), Poumon (immunologie), Réplication virale (immunologie), Virulence.
- MESH :
- analyse : Antigènes viraux.
- anatomopathologie : Poumon.
- immunologie : Coronavirus du syndrome respiratoire du Moyen-Orient, Granulocytes neutrophiles, Infections à coronavirus, Pneumopathie virale, Poumon, Réplication virale.
- métabolisme : Dipeptidyl peptidase 4.
- pathogénicité : Coronavirus du syndrome respiratoire du Moyen-Orient.
- physiologie : Coronavirus du syndrome respiratoire du Moyen-Orient.
- sang : Antigènes viraux.
- virologie : Infections à coronavirus.
- Animaux, Callithrix, Charge virale, Femelle, Humains, Lapins, Macaca mulatta, Macrophages alvéolaires, Modèles animaux de maladie humaine, Mâle, Virulence.
English descriptors
- KwdEn :
- Animals, Antigens, Viral (analysis), Antigens, Viral (blood), Callithrix, Coronavirus Infections (immunology), Coronavirus Infections (virology), Dipeptidyl Peptidase 4 (metabolism), Disease Models, Animal, Female, Humans, Lung (immunology), Lung (pathology), Macaca mulatta, Macrophages, Alveolar (classification), Male, Middle East Respiratory Syndrome Coronavirus (immunology), Middle East Respiratory Syndrome Coronavirus (pathogenicity), Middle East Respiratory Syndrome Coronavirus (physiology), Neutrophils (immunology), Pneumonia, Viral (immunology), Rabbits, Viral Load, Virulence, Virus Replication (immunology).
- MESH :
- chemical , analysis : Antigens, Viral.
- chemical , blood : Antigens, Viral.
- classification : Macrophages, Alveolar.
- immunology : Coronavirus Infections, Lung, Middle East Respiratory Syndrome Coronavirus, Neutrophils, Pneumonia, Viral, Virus Replication.
- chemical , metabolism : Dipeptidyl Peptidase 4.
- pathogenicity : Middle East Respiratory Syndrome Coronavirus.
- pathology : Lung.
- physiology : Middle East Respiratory Syndrome Coronavirus.
- virology : Coronavirus Infections.
- Animals, Callithrix, Disease Models, Animal, Female, Humans, Macaca mulatta, Male, Rabbits, Viral Load, Virulence.
Abstract
Middle East respiratory syndrome coronavirus (MERS-CoV) was first identified in a human with severe pneumonia in 2012. Since then, infections have been detected in >1500 individuals, with disease severity ranging from asymptomatic to severe, fatal pneumonia. To elucidate the pathogenesis of this virus and investigate mechanisms underlying disease severity variation in the absence of autopsy data, a rhesus macaque and common marmoset model of MERS-CoV disease were analyzed. Rhesus macaques developed mild disease, and common marmosets exhibited moderate to severe, potentially lethal, disease. Both nonhuman primate species exhibited respiratory clinical signs after inoculation, which were more severe and of longer duration in the marmosets, and developed bronchointerstitial pneumonia. In marmosets, the pneumonia was more extensive, with development of severe airway lesions. Quantitative analysis showed significantly higher levels of pulmonary neutrophil infiltration and higher amounts of pulmonary viral antigen in marmosets. Pulmonary expression of the MERS-CoV receptor, dipeptidyl peptidase 4, was similar in marmosets and macaques. These results suggest that increased virus replication and the local immune response to MERS-CoV infection likely play a role in pulmonary pathology severity. Together, the rhesus macaque and common marmoset models of MERS-CoV span the wide range of disease severity reported in MERS-CoV–infected humans, which will aid in investigating MERS-CoV disease pathogenesis.
Url:
DOI: 10.1016/j.ajpath.2015.10.025
PubMed: 26724387
PubMed Central: 4816712
Affiliations:
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Munster</name><affiliation wicri:level="2"><nlm:aff id="aff1">Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, NIH, Rocky Mountain Laboratories, Hamilton, Montana</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Montana</region></placeName><wicri:cityArea>Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, NIH, Rocky Mountain Laboratories, Hamilton</wicri:cityArea></affiliation></author><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">Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, NIH, Rocky Mountain Laboratories, Hamilton, Montana</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Montana</region></placeName><wicri:cityArea>Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, NIH, Rocky Mountain Laboratories, Hamilton</wicri:cityArea></affiliation></author><author><name sortKey="De Wit, Emmie" sort="De Wit, Emmie" uniqKey="De Wit E" first="Emmie" last="De Wit">Emmie De Wit</name><affiliation wicri:level="2"><nlm:aff id="aff1">Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, NIH, Rocky Mountain Laboratories, Hamilton, Montana</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Montana</region></placeName><wicri:cityArea>Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, NIH, Rocky Mountain Laboratories, Hamilton</wicri:cityArea></affiliation></author></analytic><series><title level="j">The American Journal of Pathology</title><idno type="ISSN">0002-9440</idno><idno type="eISSN">1525-2191</idno><imprint><date when="2015">2015</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Antigens, Viral (analysis)</term><term>Antigens, Viral (blood)</term><term>Callithrix</term><term>Coronavirus Infections (immunology)</term><term>Coronavirus Infections (virology)</term><term>Dipeptidyl Peptidase 4 (metabolism)</term><term>Disease Models, Animal</term><term>Female</term><term>Humans</term><term>Lung (immunology)</term><term>Lung (pathology)</term><term>Macaca mulatta</term><term>Macrophages, Alveolar (classification)</term><term>Male</term><term>Middle East Respiratory Syndrome Coronavirus (immunology)</term><term>Middle East Respiratory Syndrome Coronavirus (pathogenicity)</term><term>Middle East Respiratory Syndrome Coronavirus (physiology)</term><term>Neutrophils (immunology)</term><term>Pneumonia, Viral (immunology)</term><term>Rabbits</term><term>Viral Load</term><term>Virulence</term><term>Virus Replication (immunology)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Animaux</term><term>Antigènes viraux (analyse)</term><term>Antigènes viraux (sang)</term><term>Callithrix</term><term>Charge virale</term><term>Coronavirus du syndrome respiratoire du Moyen-Orient (immunologie)</term><term>Coronavirus du syndrome respiratoire du Moyen-Orient (pathogénicité)</term><term>Coronavirus du syndrome respiratoire du Moyen-Orient (physiologie)</term><term>Dipeptidyl peptidase 4 (métabolisme)</term><term>Femelle</term><term>Granulocytes neutrophiles (immunologie)</term><term>Humains</term><term>Infections à coronavirus (immunologie)</term><term>Infections à coronavirus (virologie)</term><term>Lapins</term><term>Macaca mulatta</term><term>Macrophages alvéolaires ()</term><term>Modèles animaux de maladie humaine</term><term>Mâle</term><term>Pneumopathie virale (immunologie)</term><term>Poumon (anatomopathologie)</term><term>Poumon (immunologie)</term><term>Réplication virale (immunologie)</term><term>Virulence</term></keywords><keywords scheme="MESH" type="chemical" qualifier="analysis" xml:lang="en"><term>Antigens, Viral</term></keywords><keywords scheme="MESH" type="chemical" qualifier="blood" xml:lang="en"><term>Antigens, Viral</term></keywords><keywords scheme="MESH" qualifier="analyse" xml:lang="fr"><term>Antigènes viraux</term></keywords><keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr"><term>Poumon</term></keywords><keywords scheme="MESH" qualifier="classification" xml:lang="en"><term>Macrophages, Alveolar</term></keywords><keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Coronavirus du syndrome respiratoire du Moyen-Orient</term><term>Granulocytes neutrophiles</term><term>Infections à coronavirus</term><term>Pneumopathie virale</term><term>Poumon</term><term>Réplication virale</term></keywords><keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>Coronavirus Infections</term><term>Lung</term><term>Middle East Respiratory Syndrome Coronavirus</term><term>Neutrophils</term><term>Pneumonia, Viral</term><term>Virus Replication</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Dipeptidyl Peptidase 4</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Dipeptidyl peptidase 4</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>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="sang" xml:lang="fr"><term>Antigènes viraux</term></keywords><keywords scheme="MESH" qualifier="virologie" xml:lang="fr"><term>Infections à coronavirus</term></keywords><keywords scheme="MESH" qualifier="virology" xml:lang="en"><term>Coronavirus Infections</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Callithrix</term><term>Disease Models, Animal</term><term>Female</term><term>Humans</term><term>Macaca mulatta</term><term>Male</term><term>Rabbits</term><term>Viral Load</term><term>Virulence</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Callithrix</term><term>Charge virale</term><term>Femelle</term><term>Humains</term><term>Lapins</term><term>Macaca mulatta</term><term>Macrophages alvéolaires</term><term>Modèles animaux de maladie humaine</term><term>Mâle</term><term>Virulence</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Middle East respiratory syndrome coronavirus (MERS-CoV) was first identified in a human with severe pneumonia in 2012. Since then, infections have been detected in >1500 individuals, with disease severity ranging from asymptomatic to severe, fatal pneumonia. To elucidate the pathogenesis of this virus and investigate mechanisms underlying disease severity variation in the absence of autopsy data, a rhesus macaque and common marmoset model of MERS-CoV disease were analyzed. Rhesus macaques developed mild disease, and common marmosets exhibited moderate to severe, potentially lethal, disease. Both nonhuman primate species exhibited respiratory clinical signs after inoculation, which were more severe and of longer duration in the marmosets, and developed bronchointerstitial pneumonia. In marmosets, the pneumonia was more extensive, with development of severe airway lesions. Quantitative analysis showed significantly higher levels of pulmonary neutrophil infiltration and higher amounts of pulmonary viral antigen in marmosets. Pulmonary expression of the MERS-CoV receptor, dipeptidyl peptidase 4, was similar in marmosets and macaques. These results suggest that increased virus replication and the local immune response to MERS-CoV infection likely play a role in pulmonary pathology severity. Together, the rhesus macaque and common marmoset models of MERS-CoV span the wide range of disease severity reported in MERS-CoV–infected humans, which will aid in investigating MERS-CoV disease pathogenesis.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Zaki, A M" uniqKey="Zaki A">A.M. Zaki</name></author><author><name sortKey="Van Boheemen, S" uniqKey="Van Boheemen S">S. van Boheemen</name></author><author><name sortKey="Bestebroer, T M" uniqKey="Bestebroer T">T.M. Bestebroer</name></author><author><name sortKey="Osterhaus, A D" uniqKey="Osterhaus A">A.D. Osterhaus</name></author><author><name sortKey="Fouchier, R A" uniqKey="Fouchier R">R.A. 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Baseler</name><name sortKey="De Wit, Emmie" sort="De Wit, Emmie" uniqKey="De Wit E" first="Emmie" last="De Wit">Emmie De Wit</name><name sortKey="Falzarano, Darryl" sort="Falzarano, Darryl" uniqKey="Falzarano D" first="Darryl" last="Falzarano">Darryl Falzarano</name><name sortKey="Feldmann, Heinz" sort="Feldmann, Heinz" uniqKey="Feldmann H" first="Heinz" last="Feldmann">Heinz Feldmann</name><name sortKey="Munster, Vincent J" sort="Munster, Vincent J" uniqKey="Munster V" first="Vincent J." last="Munster">Vincent J. Munster</name><name sortKey="Rosenke, Rebecca" sort="Rosenke, Rebecca" uniqKey="Rosenke R" first="Rebecca" last="Rosenke">Rebecca Rosenke</name><name sortKey="Scott, Dana P" sort="Scott, Dana P" uniqKey="Scott D" first="Dana P." last="Scott">Dana P. Scott</name><name sortKey="Thomas, Tina" sort="Thomas, Tina" uniqKey="Thomas T" first="Tina" last="Thomas">Tina Thomas</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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