Generation of a transgenic mouse model of Middle East respiratory syndrome coronavirus infection and disease.
Identifieur interne : 001784 ( Main/Exploration ); précédent : 001783; suivant : 001785Generation of a transgenic mouse model of Middle East respiratory syndrome coronavirus infection and disease.
Auteurs : Anurodh Shankar Agrawal [États-Unis] ; Tania Garron [États-Unis] ; Xinrong Tao [États-Unis] ; Bi-Hung Peng [États-Unis] ; Maki Wakamiya [États-Unis] ; Teh-Sheng Chan [États-Unis] ; Robert B. Couch [États-Unis] ; Chien-Te K. Tseng [États-Unis]Source :
- Journal of virology [ 1098-5514 ] ; 2015.
Descripteurs français
- KwdFr :
- Animaux, Charge virale, Coronavirus du syndrome respiratoire du Moyen-Orient (physiologie), Dipeptidyl peptidase 4 (biosynthèse), Dipeptidyl peptidase 4 (génétique), Expression des gènes, Facteurs temps, Humains, Infections à coronavirus (anatomopathologie), Infections à coronavirus (virologie), Modèles animaux de maladie humaine, Souris transgéniques, Structures anatomiques de l'animal (virologie).
- MESH :
- anatomopathologie : Infections à coronavirus.
- biosynthèse : Dipeptidyl peptidase 4.
- génétique : Dipeptidyl peptidase 4.
- physiologie : Coronavirus du syndrome respiratoire du Moyen-Orient.
- virologie : Infections à coronavirus, Structures anatomiques de l'animal.
- Animaux, Charge virale, Expression des gènes, Facteurs temps, Humains, Modèles animaux de maladie humaine, Souris transgéniques.
English descriptors
- KwdEn :
- Animal Structures (virology), Animals, Coronavirus Infections (pathology), Coronavirus Infections (virology), Dipeptidyl Peptidase 4 (biosynthesis), Dipeptidyl Peptidase 4 (genetics), Disease Models, Animal, Gene Expression, Humans, Mice, Transgenic, Middle East Respiratory Syndrome Coronavirus (physiology), Time Factors, Viral Load.
- MESH :
- chemical , biosynthesis : Dipeptidyl Peptidase 4.
- chemical , genetics : Dipeptidyl Peptidase 4.
- pathology : Coronavirus Infections.
- physiology : Middle East Respiratory Syndrome Coronavirus.
- virology : Animal Structures, Coronavirus Infections.
- Animals, Disease Models, Animal, Gene Expression, Humans, Mice, Transgenic, Time Factors, Viral Load.
Abstract
The emergence of Middle East respiratory syndrome-coronavirus (MERS-CoV) in the Middle East since 2012 has caused more than 900 human infections with ∼40% mortality to date. Animal models are needed for studying pathogenesis and for development of preventive and therapeutic agents against MERS-CoV infection. Nonhuman primates (rhesus macaques and marmosets) are expensive models of limited availability. Although a mouse lung infection model has been described using adenovirus vectors expressing human CD26/dipeptidyl peptidase 4 (DPP4), it is believed that a transgenic mouse model is needed for MERS-CoV research. We have developed this transgenic mouse model as indicated in this study. We show that transgenic mice globally expressing hCD26/DPP4 were fully permissive to MERS-CoV infection, resulting in relentless weight loss and death within days postinfection. High infectious virus titers were recovered primarily from the lungs and brains of mice at 2 and 4 days postinfection, respectively, whereas viral RNAs were also detected in the heart, spleen, and intestine, indicating a disseminating viral infection. Infected Tg(+) mice developed a progressive pneumonia, characterized by extensive inflammatory infiltration. In contrast, an inconsistent mild perivascular cuffing was the only pathological change associated with the infected brains. Moreover, infected Tg(+) mice were able to activate genes encoding for many antiviral and inflammatory mediators within the lungs and brains, coinciding with the high levels of viral replication. This new and unique transgenic mouse model will be useful for furthering knowledge of MERS pathogenesis and for the development of vaccine and treatments against MERS-CoV infection.
DOI: 10.1128/JVI.03427-14
PubMed: 25589660
Affiliations:
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wicri:level="2"><nlm:affiliation>Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Texas</region></placeName><wicri:cityArea>Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston</wicri:cityArea></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.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Texas</region></placeName><wicri:cityArea>Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston</wicri:cityArea></affiliation></author><author><name sortKey="Tao, Xinrong" sort="Tao, Xinrong" uniqKey="Tao X" 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Animal models are needed for studying pathogenesis and for development of preventive and therapeutic agents against MERS-CoV infection. Nonhuman primates (rhesus macaques and marmosets) are expensive models of limited availability. Although a mouse lung infection model has been described using adenovirus vectors expressing human CD26/dipeptidyl peptidase 4 (DPP4), it is believed that a transgenic mouse model is needed for MERS-CoV research. We have developed this transgenic mouse model as indicated in this study. We show that transgenic mice globally expressing hCD26/DPP4 were fully permissive to MERS-CoV infection, resulting in relentless weight loss and death within days postinfection. High infectious virus titers were recovered primarily from the lungs and brains of mice at 2 and 4 days postinfection, respectively, whereas viral RNAs were also detected in the heart, spleen, and intestine, indicating a disseminating viral infection. Infected Tg(+) mice developed a progressive pneumonia, characterized by extensive inflammatory infiltration. In contrast, an inconsistent mild perivascular cuffing was the only pathological change associated with the infected brains. Moreover, infected Tg(+) mice were able to activate genes encoding for many antiviral and inflammatory mediators within the lungs and brains, coinciding with the high levels of viral replication. This new and unique transgenic mouse model will be useful for furthering knowledge of MERS pathogenesis and for the development of vaccine and treatments against MERS-CoV infection.</div></front></TEI><affiliations><list><country><li>États-Unis</li></country><region><li>Texas</li></region></list><tree><country name="États-Unis"><region name="Texas"><name sortKey="Agrawal, Anurodh Shankar" sort="Agrawal, Anurodh Shankar" uniqKey="Agrawal A" first="Anurodh Shankar" last="Agrawal">Anurodh Shankar Agrawal</name></region><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="Garron, Tania" sort="Garron, Tania" uniqKey="Garron T" first="Tania" last="Garron">Tania Garron</name><name sortKey="Peng, Bi Hung" sort="Peng, Bi Hung" uniqKey="Peng B" first="Bi-Hung" last="Peng">Bi-Hung Peng</name><name sortKey="Tao, Xinrong" sort="Tao, Xinrong" uniqKey="Tao X" first="Xinrong" last="Tao">Xinrong Tao</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></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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