Middle East Respiratory Syndrome Coronavirus Causes Multiple Organ Damage and Lethal Disease in Mice Transgenic for Human Dipeptidyl Peptidase 4
Identifieur interne : 001691 ( Main/Exploration ); précédent : 001690; suivant : 001692Middle East Respiratory Syndrome Coronavirus Causes Multiple Organ Damage and Lethal Disease in Mice Transgenic for Human Dipeptidyl Peptidase 4
Auteurs : Kun Li ; Christine Wohlford-Lenane ; Stanley Perlman ; Jincun Zhao ; Alexander K. Jewell ; Leah R. Reznikov ; Katherine N. Gibson-Corley ; David K. Meyerholz ; Paul B. MccraySource :
- The Journal of Infectious Diseases [ 0022-1899 ] ; 2015.
Descripteurs français
- KwdFr :
- ARN viral (isolement et purification), Animaux, Coronavirus du syndrome respiratoire du Moyen-Orient (physiologie), Dipeptidyl peptidase 4 (génétique), Dipeptidyl peptidase 4 (métabolisme), Humains, Infections à coronavirus (anatomopathologie), Infections à coronavirus (mortalité), Infections à coronavirus (virologie), Maladies virales du système nerveux central (anatomopathologie), Maladies virales du système nerveux central (mortalité), Maladies virales du système nerveux central (virologie), Régulation de l'expression des gènes codant pour des enzymes, Souris, Souris transgéniques.
- MESH :
- anatomopathologie : Infections à coronavirus, Maladies virales du système nerveux central.
- génétique : Dipeptidyl peptidase 4.
- isolement et purification : ARN viral.
- mortalité : Infections à coronavirus, Maladies virales du système nerveux central.
- métabolisme : Dipeptidyl peptidase 4.
- physiologie : Coronavirus du syndrome respiratoire du Moyen-Orient.
- virologie : Infections à coronavirus, Maladies virales du système nerveux central.
- Animaux, Humains, Régulation de l'expression des gènes codant pour des enzymes, Souris, Souris transgéniques.
English descriptors
- KwdEn :
- Animals, Central Nervous System Viral Diseases (mortality), Central Nervous System Viral Diseases (pathology), Central Nervous System Viral Diseases (virology), Coronavirus Infections (mortality), Coronavirus Infections (pathology), Coronavirus Infections (virology), Dipeptidyl Peptidase 4 (genetics), Dipeptidyl Peptidase 4 (metabolism), Gene Expression Regulation, Enzymologic, Humans, Mice, Mice, Transgenic, Middle East Respiratory Syndrome Coronavirus (physiology), RNA, Viral (isolation & purification).
- MESH :
- chemical , genetics : Dipeptidyl Peptidase 4.
- chemical , isolation & purification : RNA, Viral.
- chemical , metabolism : Dipeptidyl Peptidase 4.
- mortality : Central Nervous System Viral Diseases, Coronavirus Infections.
- pathology : Central Nervous System Viral Diseases, Coronavirus Infections.
- physiology : Middle East Respiratory Syndrome Coronavirus.
- virology : Central Nervous System Viral Diseases, Coronavirus Infections.
- Animals, Gene Expression Regulation, Enzymologic, Humans, Mice, Mice, Transgenic.
Abstract
Middle East respiratory syndrome coronavirus (MERS-CoV) causes life-threatening disease. Dipeptidyl peptidase 4 (DPP4) is the receptor for cell binding and entry. There is a need for small-animal models of MERS, but mice are not susceptible to MERS because murine dpp4 does not serve as a receptor. We developed transgenic mice expressing human DPP4 (hDPP4) under the control of the surfactant protein C promoter or cytokeratin 18 promoter that are susceptible to infection with MERS-CoV. Notably, mice expressing hDPP4 with the cytokeratin 18 promoter developed progressive, uniformly fatal disease following intranasal inoculation. High virus titers were present in lung and brain tissues 2 and 6 days after infection, respectively. MERS-CoV–infected lungs revealed mononuclear cell infiltration, alveolar edema, and microvascular thrombosis, with airways generally unaffected. Brain disease was observed, with the greatest involvement noted in the thalamus and brain stem. Animals immunized with a vaccine candidate were uniformly protected from lethal infection. These new mouse models of MERS-CoV should be useful for investigation of early disease mechanisms and therapeutic interventions.
Url:
DOI: 10.1093/infdis/jiv499
PubMed: 26486634
PubMed Central: 4747621
Affiliations:
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Mccray</name><affiliation><nlm:aff id="af1"><addr-line>Department of Pediatrics</addr-line></nlm:aff></affiliation><affiliation><nlm:aff id="af2"><addr-line>Department of Microbiology</addr-line></nlm:aff></affiliation></author></analytic><series><title level="j">The Journal of Infectious Diseases</title><idno type="ISSN">0022-1899</idno><idno type="eISSN">1537-6613</idno><imprint><date when="2015">2015</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Central Nervous System Viral Diseases (mortality)</term><term>Central Nervous System Viral Diseases (pathology)</term><term>Central Nervous System Viral Diseases (virology)</term><term>Coronavirus Infections (mortality)</term><term>Coronavirus Infections (pathology)</term><term>Coronavirus Infections (virology)</term><term>Dipeptidyl Peptidase 4 (genetics)</term><term>Dipeptidyl Peptidase 4 (metabolism)</term><term>Gene Expression Regulation, Enzymologic</term><term>Humans</term><term>Mice</term><term>Mice, Transgenic</term><term>Middle East Respiratory Syndrome Coronavirus (physiology)</term><term>RNA, Viral (isolation & purification)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>ARN viral (isolement et purification)</term><term>Animaux</term><term>Coronavirus du syndrome respiratoire du Moyen-Orient (physiologie)</term><term>Dipeptidyl peptidase 4 (génétique)</term><term>Dipeptidyl peptidase 4 (métabolisme)</term><term>Humains</term><term>Infections à coronavirus (anatomopathologie)</term><term>Infections à coronavirus (mortalité)</term><term>Infections à coronavirus (virologie)</term><term>Maladies virales du système nerveux central (anatomopathologie)</term><term>Maladies virales du système nerveux central (mortalité)</term><term>Maladies virales du système nerveux central (virologie)</term><term>Régulation de l'expression des gènes codant pour des enzymes</term><term>Souris</term><term>Souris transgéniques</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Dipeptidyl Peptidase 4</term></keywords><keywords scheme="MESH" type="chemical" qualifier="isolation & purification" xml:lang="en"><term>RNA, Viral</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Dipeptidyl Peptidase 4</term></keywords><keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr"><term>Infections à coronavirus</term><term>Maladies virales du système nerveux central</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Dipeptidyl peptidase 4</term></keywords><keywords scheme="MESH" qualifier="isolement et purification" xml:lang="fr"><term>ARN viral</term></keywords><keywords scheme="MESH" qualifier="mortality" xml:lang="en"><term>Central Nervous System Viral Diseases</term><term>Coronavirus Infections</term></keywords><keywords scheme="MESH" qualifier="mortalité" xml:lang="fr"><term>Infections à coronavirus</term><term>Maladies virales du système nerveux central</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Dipeptidyl peptidase 4</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Central Nervous System Viral Diseases</term><term>Coronavirus Infections</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>Maladies virales du système nerveux central</term></keywords><keywords scheme="MESH" qualifier="virology" xml:lang="en"><term>Central Nervous System Viral Diseases</term><term>Coronavirus Infections</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Gene Expression Regulation, Enzymologic</term><term>Humans</term><term>Mice</term><term>Mice, Transgenic</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Humains</term><term>Régulation de l'expression des gènes codant pour des enzymes</term><term>Souris</term><term>Souris transgéniques</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><title>Abstract</title><p>Middle East respiratory syndrome coronavirus (MERS-CoV) causes life-threatening disease. Dipeptidyl peptidase 4 (DPP4) is the receptor for cell binding and entry. There is a need for small-animal models of MERS, but mice are not susceptible to MERS because murine dpp4 does not serve as a receptor. We developed transgenic mice expressing human DPP4 (hDPP4) under the control of the surfactant protein C promoter or cytokeratin 18 promoter that are susceptible to infection with MERS-CoV. Notably, mice expressing hDPP4 with the cytokeratin 18 promoter developed progressive, uniformly fatal disease following intranasal inoculation. High virus titers were present in lung and brain tissues 2 and 6 days after infection, respectively. MERS-CoV–infected lungs revealed mononuclear cell infiltration, alveolar edema, and microvascular thrombosis, with airways generally unaffected. Brain disease was observed, with the greatest involvement noted in the thalamus and brain stem. Animals immunized with a vaccine candidate were uniformly protected from lethal infection. These new mouse models of MERS-CoV should be useful for investigation of early disease mechanisms and therapeutic interventions.</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><analytic><author><name sortKey="Raj, Vs" uniqKey="Raj V">VS Raj</name></author><author><name sortKey="Mou, H" uniqKey="Mou H">H Mou</name></author><author><name sortKey="Smits, Sl" uniqKey="Smits S">SL Smits</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zumla, Ai" uniqKey="Zumla 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Rasmussen</name></author><author><name sortKey="Falzarano, D" uniqKey="Falzarano D">D Falzarano</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Munster, Vj" uniqKey="Munster V">VJ Munster</name></author><author><name sortKey="De Wit, E" uniqKey="De Wit E">E de Wit</name></author><author><name sortKey="Feldmann, H" uniqKey="Feldmann H">H Feldmann</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Haagmans, Bl" uniqKey="Haagmans B">BL Haagmans</name></author><author><name sortKey="Van Den Brand, Jm" uniqKey="Van Den Brand J">JM van den Brand</name></author><author><name sortKey="Provacia, Lb" uniqKey="Provacia L">LB Provacia</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Adney, Dr" uniqKey="Adney D">DR Adney</name></author><author><name sortKey="Van Doremalen, N" uniqKey="Van Doremalen N">N van Doremalen</name></author><author><name sortKey="Brown, Vr" uniqKey="Brown V">VR Brown</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Jewell, Na" uniqKey="Jewell N">NA Jewell</name></author><author><name sortKey="Cline, T" uniqKey="Cline T">T Cline</name></author><author><name sortKey="Mertz, Se" uniqKey="Mertz S">SE Mertz</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Louveau, A" uniqKey="Louveau A">A Louveau</name></author><author><name sortKey="Smirnov, I" uniqKey="Smirnov I">I Smirnov</name></author><author><name sortKey="Keyes, Tj" uniqKey="Keyes T">TJ Keyes</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list></list><tree><noCountry><name sortKey="Gibson Corley, Katherine N" sort="Gibson Corley, Katherine N" uniqKey="Gibson Corley K" first="Katherine N." last="Gibson-Corley">Katherine N. Gibson-Corley</name><name sortKey="Jewell, Alexander K" sort="Jewell, Alexander K" uniqKey="Jewell A" first="Alexander K." last="Jewell">Alexander K. Jewell</name><name sortKey="Li, Kun" sort="Li, Kun" uniqKey="Li K" first="Kun" last="Li">Kun Li</name><name sortKey="Mccray, Paul B" sort="Mccray, Paul B" uniqKey="Mccray P" first="Paul B." last="Mccray">Paul B. Mccray</name><name sortKey="Meyerholz, David K" sort="Meyerholz, David K" uniqKey="Meyerholz D" first="David K." last="Meyerholz">David K. Meyerholz</name><name sortKey="Perlman, Stanley" sort="Perlman, Stanley" uniqKey="Perlman S" first="Stanley" last="Perlman">Stanley Perlman</name><name sortKey="Reznikov, Leah R" sort="Reznikov, Leah R" uniqKey="Reznikov L" first="Leah R." last="Reznikov">Leah R. Reznikov</name><name sortKey="Wohlford Lenane, Christine" sort="Wohlford Lenane, Christine" uniqKey="Wohlford Lenane C" first="Christine" last="Wohlford-Lenane">Christine Wohlford-Lenane</name><name sortKey="Zhao, Jincun" sort="Zhao, Jincun" uniqKey="Zhao J" first="Jincun" last="Zhao">Jincun Zhao</name></noCountry></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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