Acute Respiratory Infection in Human Dipeptidyl Peptidase 4-Transgenic Mice Infected with Middle East Respiratory Syndrome Coronavirus.
Identifieur interne : 002067 ( Ncbi/Checkpoint ); précédent : 002066; suivant : 002068Acute Respiratory Infection in Human Dipeptidyl Peptidase 4-Transgenic Mice Infected with Middle East Respiratory Syndrome Coronavirus.
Auteurs : Naoko Iwata-Yoshikawa [Japon] ; Tadashi Okamura [Japon] ; Yukiko Shimizu [Japon] ; Osamu Kotani [Japon] ; Hironori Sato [Japon] ; Hanako Sekimukai [Japon] ; Shuetsu Fukushi [Japon] ; Tadaki Suzuki [Japon] ; Yuko Sato [Japon] ; Makoto Takeda [Japon] ; Masato Tashiro [Japon] ; Hideki Hasegawa [Japon] ; Noriyo Nagata [Japon]Source :
- Journal of virology [ 1098-5514 ] ; 2019.
Descripteurs français
- KwdFr :
- Animaux, Cellules Vero, Coronavirus du syndrome respiratoire du Moyen-Orient (pathogénicité), Cytokines (métabolisme), Dipeptidyl peptidase 4 (métabolisme), Femelle, Infections de l'appareil respiratoire (métabolisme), Infections de l'appareil respiratoire (virologie), Infections à coronavirus (métabolisme), Infections à coronavirus (virologie), Lignée cellulaire, Macrophages (métabolisme), Macrophages (virologie), Modèles animaux de maladie humaine, Mâle, Poumon (virologie), Souris, Souris de lignée C57BL, Souris transgéniques.
- MESH :
- métabolisme : Cytokines, Dipeptidyl peptidase 4, Infections de l'appareil respiratoire, Infections à coronavirus, Macrophages.
- pathogénicité : Coronavirus du syndrome respiratoire du Moyen-Orient.
- virologie : Infections de l'appareil respiratoire, Infections à coronavirus, Macrophages, Poumon.
- Animaux, Cellules Vero, Femelle, Lignée cellulaire, Modèles animaux de maladie humaine, Mâle, Souris, Souris de lignée C57BL, Souris transgéniques.
English descriptors
- KwdEn :
- Animals, Cell Line, Chlorocebus aethiops, Coronavirus Infections (metabolism), Coronavirus Infections (virology), Cytokines (metabolism), Dipeptidyl Peptidase 4 (metabolism), Disease Models, Animal, Female, Lung (virology), Macrophages (metabolism), Macrophages (virology), Male, Mice, Mice, Inbred C57BL, Mice, Transgenic, Middle East Respiratory Syndrome Coronavirus (pathogenicity), Respiratory Tract Infections (metabolism), Respiratory Tract Infections (virology), Vero Cells.
- MESH :
- chemical , metabolism : Cytokines, Dipeptidyl Peptidase 4.
- metabolism : Coronavirus Infections, Macrophages, Respiratory Tract Infections.
- pathogenicity : Middle East Respiratory Syndrome Coronavirus.
- virology : Coronavirus Infections, Lung, Macrophages, Respiratory Tract Infections.
- Animals, Cell Line, Chlorocebus aethiops, Disease Models, Animal, Female, Male, Mice, Mice, Inbred C57BL, Mice, Transgenic, Vero Cells.
Abstract
Middle East respiratory syndrome coronavirus (MERS-CoV) infection can manifest as a mild illness, acute respiratory distress, organ failure, or death. Several animal models have been established to study disease pathogenesis and to develop vaccines and therapeutic agents. Here, we developed transgenic (Tg) mice on a C57BL/6 background; these mice expressed human CD26/dipeptidyl peptidase 4 (hDPP4), a functional receptor for MERS-CoV, under the control of an endogenous hDPP4 promoter. We then characterized this mouse model of MERS-CoV. The expression profile of hDPP4 in these mice was almost equivalent to that in human tissues, including kidney and lung; however, hDPP4 was overexpressed in murine CD3-positive cells within peripheral blood and lymphoid tissues. Intranasal inoculation of young and adult Tg mice with MERS-CoV led to infection of the lower respiratory tract and pathological evidence of acute multifocal interstitial pneumonia within 7 days, with only transient loss of body weight. However, the immunopathology in young and adult Tg mice was different. On day 5 or 7 postinoculation, lungs of adult Tg mice contained higher levels of proinflammatory cytokines and chemokines associated with migration of macrophages. These results suggest that the immunopathology of MERS-CoV infection in the Tg mouse is age dependent. The mouse model described here will increase our understanding of disease pathogenesis and host mediators that protect against MERS-CoV infection.IMPORTANCE Middle East respiratory syndrome coronavirus (MERS-CoV) infections are endemic in the Middle East and a threat to public health worldwide. Rodents are not susceptible to the virus because they do not express functional receptors; therefore, we generated a new animal model of MERS-CoV infection based on transgenic mice expressing human DPP4 (hDPP4). The pattern of hDPP4 expression in this model was similar to that in human tissues (except lymphoid tissue). In addition, MERS-CoV was limited to the respiratory tract. Here, we focused on host factors involved in immunopathology in MERS-CoV infection and clarified differences in antiviral immune responses between young and adult transgenic mice. This new small-animal model could contribute to more in-depth study of the pathology of MERS-CoV infection and aid development of suitable treatments.
DOI: 10.1128/JVI.01818-18
PubMed: 30626685
Affiliations:
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pubmed:30626685Le document en format XML
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<author><name sortKey="Suzuki, Tadaki" sort="Suzuki, Tadaki" uniqKey="Suzuki T" first="Tadaki" last="Suzuki">Tadaki Suzuki</name>
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<wicri:regionArea>Department of Pathology, National Institute of Infectious Diseases, Tokyo</wicri:regionArea>
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<author><name sortKey="Sato, Yuko" sort="Sato, Yuko" uniqKey="Sato Y" first="Yuko" last="Sato">Yuko Sato</name>
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<wicri:regionArea>Department of Pathology, National Institute of Infectious Diseases, Tokyo</wicri:regionArea>
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<author><name sortKey="Takeda, Makoto" sort="Takeda, Makoto" uniqKey="Takeda M" first="Makoto" last="Takeda">Makoto Takeda</name>
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<author><name sortKey="Tashiro, Masato" sort="Tashiro, Masato" uniqKey="Tashiro M" first="Masato" last="Tashiro">Masato Tashiro</name>
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<term>Vero Cells</term>
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<term>Coronavirus du syndrome respiratoire du Moyen-Orient (pathogénicité)</term>
<term>Cytokines (métabolisme)</term>
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<keywords scheme="MESH" qualifier="pathogenicity" xml:lang="en"><term>Middle East Respiratory Syndrome Coronavirus</term>
</keywords>
<keywords scheme="MESH" qualifier="pathogénicité" xml:lang="fr"><term>Coronavirus du syndrome respiratoire du Moyen-Orient</term>
</keywords>
<keywords scheme="MESH" qualifier="virologie" xml:lang="fr"><term>Infections de l'appareil respiratoire</term>
<term>Infections à coronavirus</term>
<term>Macrophages</term>
<term>Poumon</term>
</keywords>
<keywords scheme="MESH" qualifier="virology" xml:lang="en"><term>Coronavirus Infections</term>
<term>Lung</term>
<term>Macrophages</term>
<term>Respiratory Tract Infections</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Animals</term>
<term>Cell Line</term>
<term>Chlorocebus aethiops</term>
<term>Disease Models, Animal</term>
<term>Female</term>
<term>Male</term>
<term>Mice</term>
<term>Mice, Inbred C57BL</term>
<term>Mice, Transgenic</term>
<term>Vero Cells</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr"><term>Animaux</term>
<term>Cellules Vero</term>
<term>Femelle</term>
<term>Lignée cellulaire</term>
<term>Modèles animaux de maladie humaine</term>
<term>Mâle</term>
<term>Souris</term>
<term>Souris de lignée C57BL</term>
<term>Souris transgéniques</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en">Middle East respiratory syndrome coronavirus (MERS-CoV) infection can manifest as a mild illness, acute respiratory distress, organ failure, or death. Several animal models have been established to study disease pathogenesis and to develop vaccines and therapeutic agents. Here, we developed transgenic (Tg) mice on a C57BL/6 background; these mice expressed human CD26/dipeptidyl peptidase 4 (hDPP4), a functional receptor for MERS-CoV, under the control of an endogenous hDPP4 promoter. We then characterized this mouse model of MERS-CoV. The expression profile of hDPP4 in these mice was almost equivalent to that in human tissues, including kidney and lung; however, hDPP4 was overexpressed in murine CD3-positive cells within peripheral blood and lymphoid tissues. Intranasal inoculation of young and adult Tg mice with MERS-CoV led to infection of the lower respiratory tract and pathological evidence of acute multifocal interstitial pneumonia within 7 days, with only transient loss of body weight. However, the immunopathology in young and adult Tg mice was different. On day 5 or 7 postinoculation, lungs of adult Tg mice contained higher levels of proinflammatory cytokines and chemokines associated with migration of macrophages. These results suggest that the immunopathology of MERS-CoV infection in the Tg mouse is age dependent. The mouse model described here will increase our understanding of disease pathogenesis and host mediators that protect against MERS-CoV infection.<b>IMPORTANCE</b>
Middle East respiratory syndrome coronavirus (MERS-CoV) infections are endemic in the Middle East and a threat to public health worldwide. Rodents are not susceptible to the virus because they do not express functional receptors; therefore, we generated a new animal model of MERS-CoV infection based on transgenic mice expressing human DPP4 (hDPP4). The pattern of hDPP4 expression in this model was similar to that in human tissues (except lymphoid tissue). In addition, MERS-CoV was limited to the respiratory tract. Here, we focused on host factors involved in immunopathology in MERS-CoV infection and clarified differences in antiviral immune responses between young and adult transgenic mice. This new small-animal model could contribute to more in-depth study of the pathology of MERS-CoV infection and aid development of suitable treatments.</div>
</front>
</TEI>
<affiliations><list><country><li>Japon</li>
</country>
<region><li>Région de Kantō</li>
</region>
<settlement><li>Tokyo</li>
</settlement>
</list>
<tree><country name="Japon"><region name="Région de Kantō"><name sortKey="Iwata Yoshikawa, Naoko" sort="Iwata Yoshikawa, Naoko" uniqKey="Iwata Yoshikawa N" first="Naoko" last="Iwata-Yoshikawa">Naoko Iwata-Yoshikawa</name>
</region>
<name sortKey="Fukushi, Shuetsu" sort="Fukushi, Shuetsu" uniqKey="Fukushi S" first="Shuetsu" last="Fukushi">Shuetsu Fukushi</name>
<name sortKey="Hasegawa, Hideki" sort="Hasegawa, Hideki" uniqKey="Hasegawa H" first="Hideki" last="Hasegawa">Hideki Hasegawa</name>
<name sortKey="Kotani, Osamu" sort="Kotani, Osamu" uniqKey="Kotani O" first="Osamu" last="Kotani">Osamu Kotani</name>
<name sortKey="Nagata, Noriyo" sort="Nagata, Noriyo" uniqKey="Nagata N" first="Noriyo" last="Nagata">Noriyo Nagata</name>
<name sortKey="Okamura, Tadashi" sort="Okamura, Tadashi" uniqKey="Okamura T" first="Tadashi" last="Okamura">Tadashi Okamura</name>
<name sortKey="Sato, Hironori" sort="Sato, Hironori" uniqKey="Sato H" first="Hironori" last="Sato">Hironori Sato</name>
<name sortKey="Sato, Yuko" sort="Sato, Yuko" uniqKey="Sato Y" first="Yuko" last="Sato">Yuko Sato</name>
<name sortKey="Sekimukai, Hanako" sort="Sekimukai, Hanako" uniqKey="Sekimukai H" first="Hanako" last="Sekimukai">Hanako Sekimukai</name>
<name sortKey="Shimizu, Yukiko" sort="Shimizu, Yukiko" uniqKey="Shimizu Y" first="Yukiko" last="Shimizu">Yukiko Shimizu</name>
<name sortKey="Suzuki, Tadaki" sort="Suzuki, Tadaki" uniqKey="Suzuki T" first="Tadaki" last="Suzuki">Tadaki Suzuki</name>
<name sortKey="Takeda, Makoto" sort="Takeda, Makoto" uniqKey="Takeda M" first="Makoto" last="Takeda">Makoto Takeda</name>
<name sortKey="Tashiro, Masato" sort="Tashiro, Masato" uniqKey="Tashiro M" first="Masato" last="Tashiro">Masato Tashiro</name>
</country>
</tree>
</affiliations>
</record>
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