Rapid generation of a mouse model for Middle East respiratory syndrome.
Identifieur interne : 001589 ( Main/Exploration ); précédent : 001588; suivant : 001590Rapid generation of a mouse model for Middle East respiratory syndrome.
Auteurs : Jincun Zhao [États-Unis] ; Kun Li ; Christine Wohlford-Lenane ; Sudhakar S. Agnihothram ; Craig Fett ; Jingxian Zhao ; Michael J. Gale ; Ralph S. Baric ; Luis Enjuanes ; Tom Gallagher ; Paul B. Mccray ; Stanley PerlmanSource :
- Proceedings of the National Academy of Sciences of the United States of America [ 1091-6490 ] ; 2014.
Descripteurs français
- KwdFr :
- Animaux, Anticorps antiviraux (immunologie), Coronavirus (immunologie), Coronavirus (physiologie), Humains, Infections de l'appareil respiratoire (), Infections de l'appareil respiratoire (immunologie), Infections de l'appareil respiratoire (virologie), Infections à coronavirus (), Infections à coronavirus (immunologie), Infections à coronavirus (virologie), Interféron de type I (métabolisme), Lymphocytes T CD8+ (virologie), Modèles animaux de maladie humaine, Moyen Orient, Réactions croisées (immunologie), Souris, Souris de lignée C57BL, Syndrome respiratoire aigu sévère (immunologie), Transduction du signal (immunologie).
- MESH :
- immunologie : Anticorps antiviraux, Coronavirus, Infections de l'appareil respiratoire, Infections à coronavirus, Réactions croisées, Syndrome respiratoire aigu sévère, Transduction du signal.
- métabolisme : Interféron de type I.
- physiologie : Coronavirus.
- virologie : Infections de l'appareil respiratoire, Infections à coronavirus, Lymphocytes T CD8+.
- Animaux, Humains, Infections de l'appareil respiratoire, Infections à coronavirus, Modèles animaux de maladie humaine, Moyen Orient, Souris, Souris de lignée C57BL.
English descriptors
- KwdEn :
- Animals, Antibodies, Viral (immunology), CD8-Positive T-Lymphocytes (virology), Coronavirus (immunology), Coronavirus (physiology), Coronavirus Infections (immunology), Coronavirus Infections (prevention & control), Coronavirus Infections (virology), Cross Reactions (immunology), Disease Models, Animal, Humans, Interferon Type I (metabolism), Mice, Mice, Inbred C57BL, Middle East, Respiratory Tract Infections (immunology), Respiratory Tract Infections (prevention & control), Respiratory Tract Infections (virology), Severe Acute Respiratory Syndrome (immunology), Signal Transduction (immunology).
- MESH :
- chemical , immunology : Antibodies, Viral.
- geographic : Middle East.
- immunology : Coronavirus, Coronavirus Infections, Cross Reactions, Respiratory Tract Infections, Severe Acute Respiratory Syndrome, Signal Transduction.
- chemical , metabolism : Interferon Type I.
- physiology : Coronavirus.
- prevention & control : Coronavirus Infections, Respiratory Tract Infections.
- virology : CD8-Positive T-Lymphocytes, Coronavirus Infections, Respiratory Tract Infections.
- Animals, Disease Models, Animal, Humans, Mice, Mice, Inbred C57BL.
Abstract
In this era of continued emergence of zoonotic virus infections, the rapid development of rodent models represents a critical barrier to public health preparedness, including the testing of antivirus therapy and vaccines. The Middle East respiratory syndrome coronavirus (MERS-CoV) was recently identified as the causative agent of a severe pneumonia. Given the ability of coronavirus to rapidly adapt to new hosts, a major public health concern is that MERS-CoV will further adapt to replication in humans, triggering a pandemic. No small-animal model for this infection is currently available, but studies suggest that virus entry factors can confer virus susceptibility. Here, we show that mice were sensitized to MERS-CoV infection by prior transduction with adenoviral vectors expressing the human host-cell receptor dipeptidyl peptidase 4. Mice developed a pneumonia characterized by extensive inflammatory-cell infiltration with virus clearance occurring 6-8 d after infection. Clinical disease and histopathological changes were more severe in the absence of type-I IFN signaling whereas the T-cell response was required for virus clearance. Using these mice, we demonstrated the efficacy of a therapeutic intervention (poly I:C) and a potential vaccine [Venezuelan equine encephalitis replicon particles expressing MERS-CoV spike protein]. We also found little protective cross-reactivity between MERS-CoV and the severe acute respiratory syndrome-CoV. Our results demonstrate that this system will be useful for MERS-CoV studies and for the rapid development of relevant animal models for emerging respiratory viral infections.
DOI: 10.1073/pnas.1323279111
PubMed: 24599590
Affiliations:
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Le document en format XML
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<front><div type="abstract" xml:lang="en">In this era of continued emergence of zoonotic virus infections, the rapid development of rodent models represents a critical barrier to public health preparedness, including the testing of antivirus therapy and vaccines. The Middle East respiratory syndrome coronavirus (MERS-CoV) was recently identified as the causative agent of a severe pneumonia. Given the ability of coronavirus to rapidly adapt to new hosts, a major public health concern is that MERS-CoV will further adapt to replication in humans, triggering a pandemic. No small-animal model for this infection is currently available, but studies suggest that virus entry factors can confer virus susceptibility. Here, we show that mice were sensitized to MERS-CoV infection by prior transduction with adenoviral vectors expressing the human host-cell receptor dipeptidyl peptidase 4. Mice developed a pneumonia characterized by extensive inflammatory-cell infiltration with virus clearance occurring 6-8 d after infection. Clinical disease and histopathological changes were more severe in the absence of type-I IFN signaling whereas the T-cell response was required for virus clearance. Using these mice, we demonstrated the efficacy of a therapeutic intervention (poly I:C) and a potential vaccine [Venezuelan equine encephalitis replicon particles expressing MERS-CoV spike protein]. We also found little protective cross-reactivity between MERS-CoV and the severe acute respiratory syndrome-CoV. Our results demonstrate that this system will be useful for MERS-CoV studies and for the rapid development of relevant animal models for emerging respiratory viral infections. </div>
</front>
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