Pathogenicity and Viral Shedding of MERS-CoV in Immunocompromised Rhesus Macaques
Identifieur interne : 000864 ( Main/Exploration ); précédent : 000863; suivant : 000865Pathogenicity and Viral Shedding of MERS-CoV in Immunocompromised Rhesus Macaques
Auteurs : Joseph Prescott [États-Unis] ; Darryl Falzarano [États-Unis] ; Emmie De Wit [États-Unis] ; Kath Hardcastle [États-Unis] ; Friederike Feldmann [États-Unis] ; Elaine Haddock [États-Unis] ; Dana Scott [États-Unis] ; Heinz Feldmann [États-Unis] ; Vincent Jacobus Munster [États-Unis]Source :
- Frontiers in Immunology [ 1664-3224 ] ; 2018.
Descripteurs français
- KwdFr :
- ARN viral (isolement et purification), Animaux, Cellules Vero, Coronavirus du syndrome respiratoire du Moyen-Orient (immunologie), Coronavirus du syndrome respiratoire du Moyen-Orient (isolement et purification), Coronavirus du syndrome respiratoire du Moyen-Orient (pathogénicité), Excrétion virale (immunologie), Femelle, Humains, Infections à coronavirus (immunologie), Infections à coronavirus (virologie), Macaca mulatta, Modèles animaux de maladie humaine, Poumon (immunologie), Poumon (virologie), Réplication virale (immunologie), Sujet immunodéprimé (immunologie).
- MESH :
- immunologie : Coronavirus du syndrome respiratoire du Moyen-Orient, Excrétion virale, Infections à coronavirus, Poumon, Réplication virale, Sujet immunodéprimé.
- isolement et purification : ARN viral, Coronavirus du syndrome respiratoire du Moyen-Orient.
- pathogénicité : Coronavirus du syndrome respiratoire du Moyen-Orient.
- virologie : Infections à coronavirus, Poumon.
- Animaux, Cellules Vero, Femelle, Humains, Macaca mulatta, Modèles animaux de maladie humaine.
English descriptors
- KwdEn :
- Animals, Chlorocebus aethiops, Coronavirus Infections (immunology), Coronavirus Infections (virology), Disease Models, Animal, Female, Host Microbial Interactions (immunology), Humans, Immunocompromised Host (immunology), Lung (immunology), Lung (virology), Macaca mulatta, Middle East Respiratory Syndrome Coronavirus (immunology), Middle East Respiratory Syndrome Coronavirus (isolation & purification), Middle East Respiratory Syndrome Coronavirus (pathogenicity), RNA, Viral (isolation & purification), Vero Cells, Virus Replication (immunology), Virus Shedding (immunology).
- MESH :
- chemical , isolation & purification : RNA, Viral.
- immunology : Coronavirus Infections, Host Microbial Interactions, Immunocompromised Host, Lung, Middle East Respiratory Syndrome Coronavirus, Virus Replication, Virus Shedding.
- isolation & purification : Middle East Respiratory Syndrome Coronavirus.
- pathogenicity : Middle East Respiratory Syndrome Coronavirus.
- virology : Coronavirus Infections, Lung.
- Animals, Chlorocebus aethiops, Disease Models, Animal, Female, Humans, Macaca mulatta, Vero Cells.
Abstract
Middle East respiratory syndrome coronavirus (MERS-CoV) has recently emerged in the Middle East. Since 2012, there have been approximately 2,100 confirmed cases, with a 35% case fatality rate. Disease severity has been linked to patient health status, as people with chronic diseases or an immunocompromised status fare worse, although the mechanisms of disease have yet to be elucidated. We used the rhesus macaque model of mild MERS to investigate whether the immune response plays a role in the pathogenicity in relation to MERS-CoV shedding. Immunosuppressed macaques were inoculated with MERS-CoV and sampled daily for 6 days to assess their immune statues and to measure viral shedding and replication. Immunosuppressed macaques supported significantly higher levels of MERS-CoV replication in respiratory tissues and shed more virus, and virus disseminated to tissues outside of the respiratory tract, whereas viral RNA was confined to respiratory tissues in non-immunosuppressed animals. Despite increased viral replication, pathology in the lungs was significantly lower in immunosuppressed animals. The observation that the virus was less pathogenic in these animals suggests that disease has an immunopathogenic component and shows that inflammatory responses elicited by the virus contribute to disease.
Url:
DOI: 10.3389/fimmu.2018.00205
PubMed: 29483914
PubMed Central: 5816332
Affiliations:
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xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Hardcastle, Kath" sort="Hardcastle, Kath" uniqKey="Hardcastle K" first="Kath" last="Hardcastle">Kath Hardcastle</name><affiliation wicri:level="1"><nlm:aff id="aff2"><institution>Rocky Mountain Veterinary Branch, Division of Intramural Research, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health</institution>,<addr-line>Hamilton, MT</addr-line>,<country>United States</country></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Feldmann, Friederike" sort="Feldmann, Friederike" uniqKey="Feldmann F" first="Friederike" last="Feldmann">Friederike Feldmann</name><affiliation wicri:level="1"><nlm:aff id="aff2"><institution>Rocky Mountain Veterinary Branch, Division of Intramural Research, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health</institution>,<addr-line>Hamilton, MT</addr-line>,<country>United States</country></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Haddock, Elaine" sort="Haddock, Elaine" uniqKey="Haddock E" first="Elaine" last="Haddock">Elaine Haddock</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Laboratory of Virology, Division of Intramural Research, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health</institution>,<addr-line>Hamilton, MT</addr-line>,<country>United States</country></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Scott, Dana" sort="Scott, Dana" uniqKey="Scott D" first="Dana" last="Scott">Dana Scott</name><affiliation wicri:level="1"><nlm:aff id="aff2"><institution>Rocky Mountain Veterinary Branch, Division of Intramural Research, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health</institution>,<addr-line>Hamilton, MT</addr-line>,<country>United States</country></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Feldmann, Heinz" sort="Feldmann, Heinz" uniqKey="Feldmann H" first="Heinz" last="Feldmann">Heinz Feldmann</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Laboratory of Virology, Division of Intramural Research, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health</institution>,<addr-line>Hamilton, MT</addr-line>,<country>United States</country></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Munster, Vincent Jacobus" sort="Munster, Vincent Jacobus" uniqKey="Munster V" first="Vincent Jacobus" last="Munster">Vincent Jacobus Munster</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Laboratory of Virology, Division of Intramural Research, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health</institution>,<addr-line>Hamilton, MT</addr-line>,<country>United States</country></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author></analytic><series><title level="j">Frontiers in Immunology</title><idno type="eISSN">1664-3224</idno><imprint><date when="2018">2018</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Chlorocebus aethiops</term><term>Coronavirus Infections (immunology)</term><term>Coronavirus Infections (virology)</term><term>Disease Models, Animal</term><term>Female</term><term>Host Microbial Interactions (immunology)</term><term>Humans</term><term>Immunocompromised Host (immunology)</term><term>Lung (immunology)</term><term>Lung (virology)</term><term>Macaca mulatta</term><term>Middle East Respiratory Syndrome Coronavirus (immunology)</term><term>Middle East Respiratory Syndrome Coronavirus (isolation & purification)</term><term>Middle East Respiratory Syndrome Coronavirus (pathogenicity)</term><term>RNA, Viral (isolation & purification)</term><term>Vero Cells</term><term>Virus Replication (immunology)</term><term>Virus Shedding (immunology)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>ARN viral (isolement et purification)</term><term>Animaux</term><term>Cellules Vero</term><term>Coronavirus du syndrome respiratoire du Moyen-Orient (immunologie)</term><term>Coronavirus du syndrome respiratoire du Moyen-Orient (isolement et purification)</term><term>Coronavirus du syndrome respiratoire du Moyen-Orient (pathogénicité)</term><term>Excrétion virale (immunologie)</term><term>Femelle</term><term>Humains</term><term>Infections à coronavirus (immunologie)</term><term>Infections à coronavirus (virologie)</term><term>Macaca mulatta</term><term>Modèles animaux de maladie humaine</term><term>Poumon (immunologie)</term><term>Poumon (virologie)</term><term>Réplication virale (immunologie)</term><term>Sujet immunodéprimé (immunologie)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="isolation & purification" xml:lang="en"><term>RNA, Viral</term></keywords><keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Coronavirus du syndrome respiratoire du Moyen-Orient</term><term>Excrétion virale</term><term>Infections à coronavirus</term><term>Poumon</term><term>Réplication virale</term><term>Sujet immunodéprimé</term></keywords><keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>Coronavirus Infections</term><term>Host Microbial Interactions</term><term>Immunocompromised Host</term><term>Lung</term><term>Middle East Respiratory Syndrome Coronavirus</term><term>Virus Replication</term><term>Virus Shedding</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="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>Chlorocebus aethiops</term><term>Disease Models, Animal</term><term>Female</term><term>Humans</term><term>Macaca mulatta</term><term>Vero Cells</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Cellules Vero</term><term>Femelle</term><term>Humains</term><term>Macaca mulatta</term><term>Modèles animaux de maladie humaine</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Middle East respiratory syndrome coronavirus (MERS-CoV) has recently emerged in the Middle East. Since 2012, there have been approximately 2,100 confirmed cases, with a 35% case fatality rate. Disease severity has been linked to patient health status, as people with chronic diseases or an immunocompromised status fare worse, although the mechanisms of disease have yet to be elucidated. We used the rhesus macaque model of mild MERS to investigate whether the immune response plays a role in the pathogenicity in relation to MERS-CoV shedding. Immunosuppressed macaques were inoculated with MERS-CoV and sampled daily for 6 days to assess their immune statues and to measure viral shedding and replication. Immunosuppressed macaques supported significantly higher levels of MERS-CoV replication in respiratory tissues and shed more virus, and virus disseminated to tissues outside of the respiratory tract, whereas viral RNA was confined to respiratory tissues in non-immunosuppressed animals. Despite increased viral replication, pathology in the lungs was significantly lower in immunosuppressed animals. The observation that the virus was less pathogenic in these animals suggests that disease has an immunopathogenic component and shows that inflammatory responses elicited by the virus contribute to disease.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Zaki, Am" uniqKey="Zaki A">AM Zaki</name></author><author><name sortKey="Van Boheemen, S" uniqKey="Van Boheemen S">S van Boheemen</name></author><author><name sortKey="Bestebroer, Tm" uniqKey="Bestebroer T">TM Bestebroer</name></author><author><name sortKey="Osterhaus, Ad" uniqKey="Osterhaus A">AD Osterhaus</name></author><author><name sortKey="Fouchier, Ra" uniqKey="Fouchier R">RA Fouchier</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="De Wit, E" uniqKey="De Wit E">E de Wit</name></author><author><name sortKey="Van Doremalen, N" uniqKey="Van Doremalen N">N van Doremalen</name></author><author><name sortKey="Falzarano, 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sortKey="Seilmaier, M" uniqKey="Seilmaier M">M Seilmaier</name></author><author><name sortKey="Corman, V" uniqKey="Corman V">V Corman</name></author><author><name sortKey="Hartmann, W" uniqKey="Hartmann W">W Hartmann</name></author><author><name sortKey="Scheible, G" uniqKey="Scheible G">G Scheible</name></author><author><name sortKey="Sack, S" uniqKey="Sack S">S Sack</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>États-Unis</li></country></list><tree><country name="États-Unis"><noRegion><name sortKey="Prescott, Joseph" sort="Prescott, Joseph" uniqKey="Prescott J" first="Joseph" last="Prescott">Joseph Prescott</name></noRegion><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, Friederike" sort="Feldmann, Friederike" uniqKey="Feldmann F" first="Friederike" last="Feldmann">Friederike Feldmann</name><name sortKey="Feldmann, Heinz" sort="Feldmann, Heinz" uniqKey="Feldmann H" first="Heinz" last="Feldmann">Heinz Feldmann</name><name sortKey="Haddock, Elaine" sort="Haddock, Elaine" uniqKey="Haddock E" first="Elaine" last="Haddock">Elaine Haddock</name><name sortKey="Hardcastle, Kath" sort="Hardcastle, Kath" uniqKey="Hardcastle K" first="Kath" last="Hardcastle">Kath Hardcastle</name><name sortKey="Munster, Vincent Jacobus" sort="Munster, Vincent Jacobus" uniqKey="Munster V" first="Vincent Jacobus" last="Munster">Vincent Jacobus Munster</name><name sortKey="Scott, Dana" sort="Scott, Dana" uniqKey="Scott D" first="Dana" last="Scott">Dana Scott</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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