Characterization and Demonstration of the Value of a Lethal Mouse Model of Middle East Respiratory Syndrome Coronavirus Infection and Disease.
Identifieur interne : 001347 ( Main/Exploration ); précédent : 001346; suivant : 001348Characterization and Demonstration of the Value of a Lethal Mouse Model of Middle East Respiratory Syndrome Coronavirus Infection and Disease.
Auteurs : Xinrong Tao [États-Unis] ; Tania Garron [États-Unis] ; Anurodh Shankar Agrawal [États-Unis] ; Abdullah Algaissi [Arabie saoudite] ; Bi-Hung Peng [États-Unis] ; Maki Wakamiya [États-Unis] ; Teh-Sheng Chan [États-Unis] ; Lu Lu [République populaire de Chine] ; Lanying Du [États-Unis] ; Shibo Jiang [États-Unis] ; Robert B. Couch [États-Unis] ; Chien-Te K. Tseng [États-Unis]Source :
- Journal of virology [ 1098-5514 ] ; 2016.
Descripteurs français
- KwdFr :
- Analyse de survie, Animaux, Anticorps antiviraux (sang), Anticorps neutralisants (sang), Antiviraux (administration et posologie), Coronavirus du syndrome respiratoire du Moyen-Orient (croissance et développement), Coronavirus du syndrome respiratoire du Moyen-Orient (immunologie), Dose létale 50, Encéphale (anatomopathologie), Encéphale (virologie), Foie (anatomopathologie), Foie (virologie), Histocytochimie, Humains, Infections à coronavirus (), Infections à coronavirus (anatomopathologie), Infections à coronavirus (traitement médicamenteux), Infections à coronavirus (virologie), Modèles animaux de maladie humaine, Poumon (anatomopathologie), Poumon (virologie), Résultat thérapeutique, Souris transgéniques, Structures anatomiques de l'animal (anatomopathologie), Structures anatomiques de l'animal (virologie), Vaccins antiviraux (administration et posologie), Vaccins antiviraux (immunologie), Évaluation préclinique de médicament ().
- MESH :
- administration et posologie : Antiviraux, Vaccins antiviraux.
- anatomopathologie : Encéphale, Foie, Infections à coronavirus, Poumon, Structures anatomiques de l'animal.
- croissance et développement : Coronavirus du syndrome respiratoire du Moyen-Orient.
- immunologie : Coronavirus du syndrome respiratoire du Moyen-Orient, Vaccins antiviraux.
- sang : Anticorps antiviraux, Anticorps neutralisants.
- traitement médicamenteux : Infections à coronavirus.
- virologie : Encéphale, Foie, Infections à coronavirus, Poumon, Structures anatomiques de l'animal.
- Analyse de survie, Animaux, Dose létale 50, Histocytochimie, Humains, Infections à coronavirus, Modèles animaux de maladie humaine, Résultat thérapeutique, Souris transgéniques, Évaluation préclinique de médicament.
English descriptors
- KwdEn :
- Animal Structures (pathology), Animal Structures (virology), Animals, Antibodies, Neutralizing (blood), Antibodies, Viral (blood), Antiviral Agents (administration & dosage), Brain (pathology), Brain (virology), Coronavirus Infections (drug therapy), Coronavirus Infections (pathology), Coronavirus Infections (prevention & control), Coronavirus Infections (virology), Disease Models, Animal, Drug Evaluation, Preclinical (methods), Histocytochemistry, Humans, Lethal Dose 50, Liver (pathology), Liver (virology), Lung (pathology), Lung (virology), Mice, Transgenic, Middle East Respiratory Syndrome Coronavirus (growth & development), Middle East Respiratory Syndrome Coronavirus (immunology), Survival Analysis, Treatment Outcome, Viral Vaccines (administration & dosage), Viral Vaccines (immunology).
- MESH :
- chemical , administration & dosage : Antiviral Agents, Viral Vaccines.
- chemical , blood : Antibodies, Neutralizing, Antibodies, Viral.
- drug therapy : Coronavirus Infections.
- growth & development : Middle East Respiratory Syndrome Coronavirus.
- immunology : Middle East Respiratory Syndrome Coronavirus, Viral Vaccines.
- methods : Drug Evaluation, Preclinical.
- pathology : Animal Structures, Brain, Coronavirus Infections, Liver, Lung.
- prevention & control : Coronavirus Infections.
- virology : Animal Structures, Brain, Coronavirus Infections, Liver, Lung.
- Animals, Disease Models, Animal, Histocytochemistry, Humans, Lethal Dose 50, Mice, Transgenic, Survival Analysis, Treatment Outcome.
Abstract
Characterized animal models are needed for studying the pathogenesis of and evaluating medical countermeasures for persisting Middle East respiratory syndrome-coronavirus (MERS-CoV) infections. Here, we further characterized a lethal transgenic mouse model of MERS-CoV infection and disease that globally expresses human CD26 (hCD26)/DPP4. The 50% infectious dose (ID50) and lethal dose (LD50) of virus were estimated to be <1 and 10 TCID50 of MERS-CoV, respectively. Neutralizing antibody developed in the surviving mice from the ID50/LD50 determinations, and all were fully immune to challenge with 100 LD50 of MERS-CoV. The tissue distribution and histopathology in mice challenged with a potential working dose of 10 LD50 of MERS-CoV were subsequently evaluated. In contrast to the overwhelming infection seen in the mice challenged with 10(5) LD50 of MERS-CoV, we were able to recover infectious virus from these mice only infrequently, although quantitative reverse transcription-PCR (qRT-PCR) tests indicated early and persistent lung infection and delayed occurrence of brain infection. Persistent inflammatory infiltrates were seen in the lungs and brain stems at day 2 and day 6 after infection, respectively. While focal infiltrates were also noted in the liver, definite pathology was not seen in other tissues. Finally, using a receptor binding domain protein vaccine and a MERS-CoV fusion inhibitor, we demonstrated the value of this model for evaluating vaccines and antivirals against MERS. As outcomes of MERS-CoV infection in patients differ greatly, ranging from asymptomatic to overwhelming disease and death, having available both an infection model and a lethal model makes this transgenic mouse model relevant for advancing MERS research.
DOI: 10.1128/JVI.02009-15
PubMed: 26446606
Affiliations:
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wicri:level="2"><nlm:affiliation>Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas</wicri:regionArea><placeName><region type="state">Texas</region></placeName></affiliation></author><author><name sortKey="Garron, Tania" sort="Garron, Tania" uniqKey="Garron T" first="Tania" last="Garron">Tania Garron</name><affiliation wicri:level="2"><nlm:affiliation>Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas</wicri:regionArea><placeName><region type="state">Texas</region></placeName></affiliation></author><author><name sortKey="Agrawal, Anurodh Shankar" sort="Agrawal, Anurodh Shankar" uniqKey="Agrawal A" first="Anurodh Shankar" last="Agrawal">Anurodh Shankar Agrawal</name><affiliation wicri:level="2"><nlm:affiliation>Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas</wicri:regionArea><placeName><region type="state">Texas</region></placeName></affiliation></author><author><name sortKey="Algaissi, Abdullah" sort="Algaissi, Abdullah" uniqKey="Algaissi A" first="Abdullah" last="Algaissi">Abdullah Algaissi</name><affiliation wicri:level="1"><nlm:affiliation>Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, USA Department of Medical Laboratories Technology, College of Applied Medical Sciences, Jazan University, Jazan, Saudi Arabia.</nlm:affiliation><country xml:lang="fr">Arabie saoudite</country><wicri:regionArea>Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, USA Department of Medical Laboratories Technology, College of Applied Medical Sciences, Jazan University, Jazan</wicri:regionArea><wicri:noRegion>Jazan</wicri:noRegion></affiliation></author><author><name sortKey="Peng, Bi Hung" sort="Peng, Bi Hung" uniqKey="Peng B" first="Bi-Hung" last="Peng">Bi-Hung Peng</name><affiliation wicri:level="2"><nlm:affiliation>Department of Pathology, University of Texas Medical Branch, Galveston, Texas, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pathology, University of Texas Medical Branch, Galveston, Texas</wicri:regionArea><placeName><region type="state">Texas</region></placeName></affiliation></author><author><name sortKey="Wakamiya, Maki" sort="Wakamiya, Maki" uniqKey="Wakamiya M" first="Maki" last="Wakamiya">Maki Wakamiya</name><affiliation wicri:level="2"><nlm:affiliation>Transgenic Mouse Core Facility, Institute for Translational Sciences and Animal Resource Center, University of Texas Medical Branch, Galveston, Texas, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Transgenic Mouse Core Facility, Institute for Translational Sciences and Animal Resource Center, University of Texas Medical Branch, Galveston, Texas</wicri:regionArea><placeName><region type="state">Texas</region></placeName></affiliation></author><author><name sortKey="Chan, Teh Sheng" sort="Chan, Teh Sheng" uniqKey="Chan T" first="Teh-Sheng" last="Chan">Teh-Sheng Chan</name><affiliation wicri:level="2"><nlm:affiliation>Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas</wicri:regionArea><placeName><region type="state">Texas</region></placeName></affiliation></author><author><name sortKey="Lu, Lu" sort="Lu, Lu" uniqKey="Lu L" first="Lu" last="Lu">Lu Lu</name><affiliation wicri:level="1"><nlm:affiliation>Institute of Medical Microbiology, Fudan University, Shanghai, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Institute of Medical Microbiology, Fudan University, Shanghai</wicri:regionArea><wicri:noRegion>Shanghai</wicri:noRegion></affiliation></author><author><name sortKey="Du, Lanying" sort="Du, Lanying" uniqKey="Du L" first="Lanying" last="Du">Lanying Du</name><affiliation wicri:level="2"><nlm:affiliation>Lindsley F. Kimball Research Institute, New York Blood Center, New York, New York, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Lindsley F. Kimball Research Institute, New York Blood Center, New York, New York</wicri:regionArea><placeName><region type="state">État de New York</region></placeName></affiliation></author><author><name sortKey="Jiang, Shibo" sort="Jiang, Shibo" uniqKey="Jiang S" first="Shibo" last="Jiang">Shibo Jiang</name><affiliation wicri:level="2"><nlm:affiliation>Lindsley F. Kimball Research Institute, New York Blood Center, New York, New York, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Lindsley F. Kimball Research Institute, New York Blood Center, New York, New York</wicri:regionArea><placeName><region type="state">État de New York</region></placeName></affiliation></author><author><name sortKey="Couch, Robert B" sort="Couch, Robert B" uniqKey="Couch R" first="Robert B" last="Couch">Robert B. Couch</name><affiliation wicri:level="2"><nlm:affiliation>Department of Internal Medicine, Division of Infectious Disease, University of Texas Medical Branch, Galveston, Texas, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Internal Medicine, Division of Infectious Disease, University of Texas Medical Branch, Galveston, Texas</wicri:regionArea><placeName><region type="state">Texas</region></placeName></affiliation></author><author><name sortKey="Tseng, Chien Te K" sort="Tseng, Chien Te K" uniqKey="Tseng C" first="Chien-Te K" last="Tseng">Chien-Te K. Tseng</name><affiliation wicri:level="2"><nlm:affiliation>Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, USA Center for Biodefense and Emerging Infectious Disease, University of Texas Medical Branch, Galveston, Texas, USA sktseng@utmb.edu.</nlm:affiliation><country wicri:rule="url">États-Unis</country><wicri:regionArea>Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, USA Center for Biodefense and Emerging Infectious Disease, University of Texas Medical Branch, Galveston, Texas</wicri:regionArea><placeName><region type="state">Texas</region></placeName></affiliation></author></analytic><series><title level="j">Journal of virology</title><idno type="eISSN">1098-5514</idno><imprint><date when="2016" type="published">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animal Structures (pathology)</term><term>Animal Structures (virology)</term><term>Animals</term><term>Antibodies, Neutralizing (blood)</term><term>Antibodies, Viral (blood)</term><term>Antiviral Agents (administration & dosage)</term><term>Brain (pathology)</term><term>Brain (virology)</term><term>Coronavirus Infections (drug therapy)</term><term>Coronavirus Infections (pathology)</term><term>Coronavirus Infections (prevention & control)</term><term>Coronavirus Infections (virology)</term><term>Disease Models, Animal</term><term>Drug Evaluation, Preclinical (methods)</term><term>Histocytochemistry</term><term>Humans</term><term>Lethal Dose 50</term><term>Liver (pathology)</term><term>Liver (virology)</term><term>Lung (pathology)</term><term>Lung (virology)</term><term>Mice, Transgenic</term><term>Middle East Respiratory Syndrome Coronavirus (growth & development)</term><term>Middle East Respiratory Syndrome Coronavirus (immunology)</term><term>Survival Analysis</term><term>Treatment Outcome</term><term>Viral Vaccines (administration & dosage)</term><term>Viral Vaccines (immunology)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Analyse de survie</term><term>Animaux</term><term>Anticorps antiviraux (sang)</term><term>Anticorps neutralisants (sang)</term><term>Antiviraux (administration et posologie)</term><term>Coronavirus du syndrome respiratoire du Moyen-Orient (croissance et développement)</term><term>Coronavirus du syndrome respiratoire du Moyen-Orient (immunologie)</term><term>Dose létale 50</term><term>Encéphale (anatomopathologie)</term><term>Encéphale (virologie)</term><term>Foie (anatomopathologie)</term><term>Foie (virologie)</term><term>Histocytochimie</term><term>Humains</term><term>Infections à coronavirus ()</term><term>Infections à coronavirus (anatomopathologie)</term><term>Infections à coronavirus (traitement médicamenteux)</term><term>Infections à coronavirus (virologie)</term><term>Modèles animaux de maladie humaine</term><term>Poumon (anatomopathologie)</term><term>Poumon (virologie)</term><term>Résultat thérapeutique</term><term>Souris transgéniques</term><term>Structures anatomiques de l'animal (anatomopathologie)</term><term>Structures anatomiques de l'animal (virologie)</term><term>Vaccins antiviraux (administration et posologie)</term><term>Vaccins antiviraux (immunologie)</term><term>Évaluation préclinique de médicament ()</term></keywords><keywords scheme="MESH" type="chemical" qualifier="administration & dosage" xml:lang="en"><term>Antiviral Agents</term><term>Viral Vaccines</term></keywords><keywords scheme="MESH" type="chemical" qualifier="blood" xml:lang="en"><term>Antibodies, Neutralizing</term><term>Antibodies, Viral</term></keywords><keywords scheme="MESH" qualifier="administration et posologie" xml:lang="fr"><term>Antiviraux</term><term>Vaccins antiviraux</term></keywords><keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr"><term>Encéphale</term><term>Foie</term><term>Infections à coronavirus</term><term>Poumon</term><term>Structures anatomiques de l'animal</term></keywords><keywords scheme="MESH" qualifier="croissance et développement" xml:lang="fr"><term>Coronavirus du syndrome respiratoire du Moyen-Orient</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Coronavirus Infections</term></keywords><keywords scheme="MESH" qualifier="growth & development" xml:lang="en"><term>Middle East Respiratory Syndrome Coronavirus</term></keywords><keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Coronavirus du syndrome respiratoire du Moyen-Orient</term><term>Vaccins antiviraux</term></keywords><keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>Middle East Respiratory Syndrome Coronavirus</term><term>Viral Vaccines</term></keywords><keywords scheme="MESH" qualifier="methods" xml:lang="en"><term>Drug Evaluation, Preclinical</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Animal Structures</term><term>Brain</term><term>Coronavirus Infections</term><term>Liver</term><term>Lung</term></keywords><keywords scheme="MESH" qualifier="prevention & control" xml:lang="en"><term>Coronavirus Infections</term></keywords><keywords scheme="MESH" qualifier="sang" xml:lang="fr"><term>Anticorps antiviraux</term><term>Anticorps neutralisants</term></keywords><keywords scheme="MESH" qualifier="traitement médicamenteux" xml:lang="fr"><term>Infections à coronavirus</term></keywords><keywords scheme="MESH" qualifier="virologie" xml:lang="fr"><term>Encéphale</term><term>Foie</term><term>Infections à coronavirus</term><term>Poumon</term><term>Structures anatomiques de l'animal</term></keywords><keywords scheme="MESH" qualifier="virology" xml:lang="en"><term>Animal Structures</term><term>Brain</term><term>Coronavirus Infections</term><term>Liver</term><term>Lung</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Disease Models, Animal</term><term>Histocytochemistry</term><term>Humans</term><term>Lethal Dose 50</term><term>Mice, Transgenic</term><term>Survival Analysis</term><term>Treatment Outcome</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Analyse de survie</term><term>Animaux</term><term>Dose létale 50</term><term>Histocytochimie</term><term>Humains</term><term>Infections à coronavirus</term><term>Modèles animaux de maladie humaine</term><term>Résultat thérapeutique</term><term>Souris transgéniques</term><term>Évaluation préclinique de médicament</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Characterized animal models are needed for studying the pathogenesis of and evaluating medical countermeasures for persisting Middle East respiratory syndrome-coronavirus (MERS-CoV) infections. Here, we further characterized a lethal transgenic mouse model of MERS-CoV infection and disease that globally expresses human CD26 (hCD26)/DPP4. The 50% infectious dose (ID50) and lethal dose (LD50) of virus were estimated to be <1 and 10 TCID50 of MERS-CoV, respectively. Neutralizing antibody developed in the surviving mice from the ID50/LD50 determinations, and all were fully immune to challenge with 100 LD50 of MERS-CoV. The tissue distribution and histopathology in mice challenged with a potential working dose of 10 LD50 of MERS-CoV were subsequently evaluated. In contrast to the overwhelming infection seen in the mice challenged with 10(5) LD50 of MERS-CoV, we were able to recover infectious virus from these mice only infrequently, although quantitative reverse transcription-PCR (qRT-PCR) tests indicated early and persistent lung infection and delayed occurrence of brain infection. Persistent inflammatory infiltrates were seen in the lungs and brain stems at day 2 and day 6 after infection, respectively. While focal infiltrates were also noted in the liver, definite pathology was not seen in other tissues. Finally, using a receptor binding domain protein vaccine and a MERS-CoV fusion inhibitor, we demonstrated the value of this model for evaluating vaccines and antivirals against MERS. As outcomes of MERS-CoV infection in patients differ greatly, ranging from asymptomatic to overwhelming disease and death, having available both an infection model and a lethal model makes this transgenic mouse model relevant for advancing MERS research.</div></front></TEI><affiliations><list><country><li>Arabie saoudite</li><li>République populaire de Chine</li><li>États-Unis</li></country><region><li>Texas</li><li>État de New York</li></region></list><tree><country name="États-Unis"><region name="Texas"><name sortKey="Tao, Xinrong" sort="Tao, Xinrong" uniqKey="Tao X" first="Xinrong" last="Tao">Xinrong Tao</name></region><name sortKey="Agrawal, Anurodh Shankar" sort="Agrawal, Anurodh Shankar" uniqKey="Agrawal A" first="Anurodh Shankar" last="Agrawal">Anurodh Shankar Agrawal</name><name sortKey="Chan, Teh Sheng" sort="Chan, Teh Sheng" uniqKey="Chan T" first="Teh-Sheng" last="Chan">Teh-Sheng Chan</name><name sortKey="Couch, Robert B" sort="Couch, Robert B" uniqKey="Couch R" first="Robert B" last="Couch">Robert B. Couch</name><name sortKey="Du, Lanying" sort="Du, Lanying" uniqKey="Du L" first="Lanying" last="Du">Lanying Du</name><name sortKey="Garron, Tania" sort="Garron, Tania" uniqKey="Garron T" first="Tania" last="Garron">Tania Garron</name><name sortKey="Jiang, Shibo" sort="Jiang, Shibo" uniqKey="Jiang S" first="Shibo" last="Jiang">Shibo Jiang</name><name sortKey="Peng, Bi Hung" sort="Peng, Bi Hung" uniqKey="Peng B" first="Bi-Hung" last="Peng">Bi-Hung Peng</name><name sortKey="Tseng, Chien Te K" sort="Tseng, Chien Te K" uniqKey="Tseng C" first="Chien-Te K" last="Tseng">Chien-Te K. Tseng</name><name sortKey="Wakamiya, Maki" sort="Wakamiya, Maki" uniqKey="Wakamiya M" first="Maki" last="Wakamiya">Maki Wakamiya</name></country><country name="Arabie saoudite"><noRegion><name sortKey="Algaissi, Abdullah" sort="Algaissi, Abdullah" uniqKey="Algaissi A" first="Abdullah" last="Algaissi">Abdullah Algaissi</name></noRegion></country><country name="République populaire de Chine"><noRegion><name sortKey="Lu, Lu" sort="Lu, Lu" uniqKey="Lu L" first="Lu" last="Lu">Lu Lu</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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