A Mouse Model for Betacoronavirus Subgroup 2c Using a Bat Coronavirus Strain HKU5 Variant
Identifieur interne : 001D66 ( Main/Exploration ); précédent : 001D65; suivant : 001D67A Mouse Model for Betacoronavirus Subgroup 2c Using a Bat Coronavirus Strain HKU5 Variant
Auteurs : Sudhakar Agnihothram ; Boyd L. Yount ; Eric F. Donaldson ; Jeremy Huynh ; Vineet D. Menachery ; Lisa E. Gralinski ; Rachel L. Graham ; Michelle M. Becker ; Sakshi Tomar ; Trevor D. Scobey ; Heather L. Osswald ; Alan Whitmore ; Robin Gopal ; Arun K. Ghosh ; Andrew Mesecar ; Maria Zambon ; Mark Heise ; Mark R. Denison ; Ralph S. BaricSource :
- mBio [ 2150-7511 ] ; 2014.
Descripteurs français
- KwdFr :
- Animaux, Appareil respiratoire (virologie), Chiroptera, Coronavirus (isolement et purification), Coronavirus (pathogénicité), Coronavirus (physiologie), Infections à coronavirus (anatomopathologie), Infections à coronavirus (virologie), Modèles animaux de maladie humaine, Souris, Souris de lignée BALB C, Vaccins antiviraux (effets indésirables), Vaccins antiviraux (génétique), Vaccins antiviraux (immunologie), Vaccins synthétiques (effets indésirables), Vaccins synthétiques (génétique), Vaccins synthétiques (immunologie), Vecteurs de médicaments, Vecteurs génétiques, Virus de l'encéphalite équine du Venezuela (génétique), Éosinophilie (immunologie).
- MESH :
- anatomopathologie : Infections à coronavirus.
- effets indésirables : Vaccins antiviraux, Vaccins synthétiques.
- génétique : Vaccins antiviraux, Vaccins synthétiques, Virus de l'encéphalite équine du Venezuela.
- immunologie : Vaccins antiviraux, Vaccins synthétiques, Éosinophilie.
- isolement et purification : Coronavirus.
- pathogénicité : Coronavirus.
- physiologie : Coronavirus.
- virologie : Appareil respiratoire, Infections à coronavirus.
- Animaux, Chiroptera, Modèles animaux de maladie humaine, Souris, Souris de lignée BALB C, Vecteurs de médicaments, Vecteurs génétiques.
English descriptors
- KwdEn :
- Animals, Chiroptera, Coronavirus (isolation & purification), Coronavirus (pathogenicity), Coronavirus (physiology), Coronavirus Infections (pathology), Coronavirus Infections (virology), Disease Models, Animal, Drug Carriers, Encephalitis Virus, Venezuelan Equine (genetics), Eosinophilia (immunology), Genetic Vectors, Mice, Mice, Inbred BALB C, Respiratory System (virology), Vaccines, Synthetic (adverse effects), Vaccines, Synthetic (genetics), Vaccines, Synthetic (immunology), Viral Vaccines (adverse effects), Viral Vaccines (genetics), Viral Vaccines (immunology).
- MESH :
- chemical , adverse effects : Vaccines, Synthetic, Viral Vaccines.
- chemical , genetics : Vaccines, Synthetic, Viral Vaccines.
- chemical , immunology : Vaccines, Synthetic, Viral Vaccines.
- chemical : Drug Carriers.
- genetics : Encephalitis Virus, Venezuelan Equine.
- immunology : Eosinophilia.
- isolation & purification : Coronavirus.
- pathogenicity : Coronavirus.
- pathology : Coronavirus Infections.
- physiology : Coronavirus.
- virology : Coronavirus Infections, Respiratory System.
- Animals, Chiroptera, Disease Models, Animal, Genetic Vectors, Mice, Mice, Inbred BALB C.
Abstract
Cross-species transmission of zoonotic coronaviruses (CoVs) can result in pandemic disease outbreaks. Middle East respiratory syndrome CoV (MERS-CoV), identified in 2012, has caused 182 cases to date, with ~43% mortality, and no small animal model has been reported. MERS-CoV and
Url:
DOI: 10.1128/mBio.00047-14
PubMed: 24667706
PubMed Central: 3977350
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 Mouse Model for <italic>Betacoronavirus</italic>
Subgroup 2c Using a Bat Coronavirus Strain HKU5 Variant</title>
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<term>Chiroptera</term>
<term>Coronavirus (isolation & purification)</term>
<term>Coronavirus (pathogenicity)</term>
<term>Coronavirus (physiology)</term>
<term>Coronavirus Infections (pathology)</term>
<term>Coronavirus Infections (virology)</term>
<term>Disease Models, Animal</term>
<term>Drug Carriers</term>
<term>Encephalitis Virus, Venezuelan Equine (genetics)</term>
<term>Eosinophilia (immunology)</term>
<term>Genetic Vectors</term>
<term>Mice</term>
<term>Mice, Inbred BALB C</term>
<term>Respiratory System (virology)</term>
<term>Vaccines, Synthetic (adverse effects)</term>
<term>Vaccines, Synthetic (genetics)</term>
<term>Vaccines, Synthetic (immunology)</term>
<term>Viral Vaccines (adverse effects)</term>
<term>Viral Vaccines (genetics)</term>
<term>Viral Vaccines (immunology)</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>Animaux</term>
<term>Appareil respiratoire (virologie)</term>
<term>Chiroptera</term>
<term>Coronavirus (isolement et purification)</term>
<term>Coronavirus (pathogénicité)</term>
<term>Coronavirus (physiologie)</term>
<term>Infections à coronavirus (anatomopathologie)</term>
<term>Infections à coronavirus (virologie)</term>
<term>Modèles animaux de maladie humaine</term>
<term>Souris</term>
<term>Souris de lignée BALB C</term>
<term>Vaccins antiviraux (effets indésirables)</term>
<term>Vaccins antiviraux (génétique)</term>
<term>Vaccins antiviraux (immunologie)</term>
<term>Vaccins synthétiques (effets indésirables)</term>
<term>Vaccins synthétiques (génétique)</term>
<term>Vaccins synthétiques (immunologie)</term>
<term>Vecteurs de médicaments</term>
<term>Vecteurs génétiques</term>
<term>Virus de l'encéphalite équine du Venezuela (génétique)</term>
<term>Éosinophilie (immunologie)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="adverse effects" xml:lang="en"><term>Vaccines, Synthetic</term>
<term>Viral Vaccines</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Vaccines, Synthetic</term>
<term>Viral Vaccines</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="immunology" xml:lang="en"><term>Vaccines, Synthetic</term>
<term>Viral Vaccines</term>
</keywords>
<keywords scheme="MESH" type="chemical" xml:lang="en"><term>Drug Carriers</term>
</keywords>
<keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr"><term>Infections à coronavirus</term>
</keywords>
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<term>Vaccins synthétiques</term>
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<term>Vaccins synthétiques</term>
<term>Virus de l'encéphalite équine du Venezuela</term>
</keywords>
<keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Vaccins antiviraux</term>
<term>Vaccins synthétiques</term>
<term>Éosinophilie</term>
</keywords>
<keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>Eosinophilia</term>
</keywords>
<keywords scheme="MESH" qualifier="isolation & purification" xml:lang="en"><term>Coronavirus</term>
</keywords>
<keywords scheme="MESH" qualifier="isolement et purification" xml:lang="fr"><term>Coronavirus</term>
</keywords>
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</keywords>
<keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>Coronavirus</term>
</keywords>
<keywords scheme="MESH" qualifier="virologie" xml:lang="fr"><term>Appareil respiratoire</term>
<term>Infections à coronavirus</term>
</keywords>
<keywords scheme="MESH" qualifier="virology" xml:lang="en"><term>Coronavirus Infections</term>
<term>Respiratory System</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Animals</term>
<term>Chiroptera</term>
<term>Disease Models, Animal</term>
<term>Genetic Vectors</term>
<term>Mice</term>
<term>Mice, Inbred BALB C</term>
</keywords>
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<term>Chiroptera</term>
<term>Modèles animaux de maladie humaine</term>
<term>Souris</term>
<term>Souris de lignée BALB C</term>
<term>Vecteurs de médicaments</term>
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<front><div type="abstract" xml:lang="en"><title>ABSTRACT</title>
<p>Cross-species transmission of zoonotic coronaviruses (CoVs) can result in pandemic disease outbreaks. Middle East respiratory syndrome CoV (MERS-CoV), identified in 2012, has caused 182 cases to date, with ~43% mortality, and no small animal model has been reported. MERS-CoV and <italic>Pipistrellus</italic>
bat coronavirus (BtCoV) strain HKU5 of <italic>Betacoronavirus</italic>
(β-CoV) subgroup 2c share >65% identity at the amino acid level in several regions, including nonstructural protein 5 (nsp5) and the nucleocapsid (N) protein, which are significant drug and vaccine targets. BtCoV HKU5 has been described <italic>in silico</italic>
but has not been shown to replicate in culture, thus hampering drug and vaccine studies against subgroup 2c β-CoVs. We report the synthetic reconstruction and testing of BtCoV HKU5 containing the severe acute respiratory syndrome (SARS)-CoV <underline>s</underline>
pike (S) glycoprotein <underline>e</underline>
ctodomain (BtCoV HKU5-SE). This virus replicates efficiently in cell culture and in young and aged mice, where the virus targets airway and alveolar epithelial cells. Unlike some subgroup 2b SARS-CoV vaccines that elicit a strong eosinophilia following challenge, we demonstrate that BtCoV HKU5 and MERS-CoV N-expressing Venezuelan equine encephalitis <underline>v</underline>
irus <underline>r</underline>
eplicon <underline>p</underline>
article (VRP) vaccines do not cause extensive eosinophilia following BtCoV HKU5-SE challenge. Passage of BtCoV HKU5-SE in young mice resulted in enhanced virulence, causing 20% weight loss, diffuse alveolar damage, and hyaline membrane formation in aged mice. Passaged virus was characterized by mutations in the nsp13, nsp14, open reading frame 5 (ORF5) and M genes. Finally, we identified an inhibitor active against the nsp5 proteases of subgroup 2c β-CoVs. Synthetic-genome platforms capable of reconstituting emerging zoonotic viral pathogens or their phylogenetic relatives provide new strategies for identifying broad-based therapeutics, evaluating vaccine outcomes, and studying viral pathogenesis.</p>
</div>
</front>
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</author>
<author><name sortKey="King, Ls" uniqKey="King L">LS King</name>
</author>
<author><name sortKey="Aggarwal, Nr" uniqKey="Aggarwal N">NR Aggarwal</name>
</author>
<author><name sortKey="De Gorordo, A" uniqKey="De Gorordo A">A De Gorordo</name>
</author>
<author><name sortKey="D Lessio, Fr" uniqKey="D Lessio F">FR D’Alessio</name>
</author>
<author><name sortKey="Kubo, K" uniqKey="Kubo K">K Kubo</name>
</author>
</analytic>
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<biblStruct><analytic><author><name sortKey="Masters, Ps" uniqKey="Masters P">PS Masters</name>
</author>
</analytic>
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<biblStruct><analytic><author><name sortKey="Graham, Rl" uniqKey="Graham R">RL Graham</name>
</author>
<author><name sortKey="Baric, Rs" uniqKey="Baric R">RS Baric</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Bolles, M" uniqKey="Bolles M">M Bolles</name>
</author>
<author><name sortKey="Donaldson, E" uniqKey="Donaldson E">E Donaldson</name>
</author>
<author><name sortKey="Baric, R" uniqKey="Baric R">R Baric</name>
</author>
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<name sortKey="Becker, Michelle M" sort="Becker, Michelle M" uniqKey="Becker M" first="Michelle M." last="Becker">Michelle M. Becker</name>
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<name sortKey="Gopal, Robin" sort="Gopal, Robin" uniqKey="Gopal R" first="Robin" last="Gopal">Robin Gopal</name>
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