The characteristics of hDPP4 transgenic mice subjected to aerosol MERS coronavirus infection via an animal nose‐only exposure device
Identifieur interne : 000A51 ( Pmc/Curation ); précédent : 000A50; suivant : 000A52The characteristics of hDPP4 transgenic mice subjected to aerosol MERS coronavirus infection via an animal nose‐only exposure device
Auteurs : Xin-Yan Hao ; Qi Lv ; Feng-Di Li ; Yan-Feng Xu ; Hong GaoSource :
- Animal Models and Experimental Medicine [ 2096-5451 ] ; 2019.
Abstract
Middle East respiratory syndrome coronavirus (MERS‐CoV), which is not fully understood in regard to certain transmission routes and pathogenesis and lacks specific therapeutics and vaccines, poses a global threat to public health.
To simulate the clinical aerosol transmission route, hDPP4 transgenic mice were infected with MERS‐CoV by an animal nose‐only exposure device and compared with instillation‐inoculated mice. The challenged mice were observed for 14 consecutive days and necropsied on days 3, 5, 7, and 9 to analyze viral load, histopathology, viral antigen distribution, and cytokines in tissues.
MERS‐CoV aerosol‐infected mice with an incubation period of 5‐7 days showed weight loss on days 7‐11, obvious lung lesions on day 7, high viral loads in the lungs on days 3‐9 and in the brain on days 7‐9, and 60% survival. MERS‐CoV instillation‐inoculated mice exhibited clinical signs on day 1, obvious lung lesions on days 3‐5, continuous weight loss, 0% survival by day 5, and high viral loads in the lungs and brain on days 3‐5. Viral antigen and high levels of proinflammatory cytokines and chemokines were detected in the aerosol and instillation groups. Disease, lung lesion, and viral replication progressions were slower in the MERS‐CoV aerosol‐infected mice than in the MERS‐CoV instillation‐inoculated mice.
hDPP4 transgenic mice were successfully infected with MERS‐CoV aerosols via an animal nose‐only exposure device, and aerosol‐ and instillation‐infected mice simulated the clinical symptoms of moderate diffuse interstitial pneumonia. However, the transgenic mice exposed to aerosol MERS‐CoV developed disease and lung pathology progressions that more closely resembled those observed in humans.
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DOI: 10.1002/ame2.12088
PubMed: 31942559
PubMed Central: 6930991
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<front><div type="abstract" xml:lang="en"><title>Abstract</title>
<sec id="ame212088-sec-0001"><title>Background</title>
<p>Middle East respiratory syndrome coronavirus (MERS‐CoV), which is not fully understood in regard to certain transmission routes and pathogenesis and lacks specific therapeutics and vaccines, poses a global threat to public health.</p>
</sec>
<sec id="ame212088-sec-0002"><title>Methods</title>
<p>To simulate the clinical aerosol transmission route, hDPP4 transgenic mice were infected with MERS‐CoV by an animal nose‐only exposure device and compared with instillation‐inoculated mice. The challenged mice were observed for 14 consecutive days and necropsied on days 3, 5, 7, and 9 to analyze viral load, histopathology, viral antigen distribution, and cytokines in tissues.</p>
</sec>
<sec id="ame212088-sec-0003"><title>Results</title>
<p>MERS‐CoV aerosol‐infected mice with an incubation period of 5‐7 days showed weight loss on days 7‐11, obvious lung lesions on day 7, high viral loads in the lungs on days 3‐9 and in the brain on days 7‐9, and 60% survival. MERS‐CoV instillation‐inoculated mice exhibited clinical signs on day 1, obvious lung lesions on days 3‐5, continuous weight loss, 0% survival by day 5, and high viral loads in the lungs and brain on days 3‐5. Viral antigen and high levels of proinflammatory cytokines and chemokines were detected in the aerosol and instillation groups. Disease, lung lesion, and viral replication progressions were slower in the MERS‐CoV aerosol‐infected mice than in the MERS‐CoV instillation‐inoculated mice.</p>
</sec>
<sec id="ame212088-sec-0004"><title>Conclusion</title>
<p>hDPP4 transgenic mice were successfully infected with MERS‐CoV aerosols via an animal nose‐only exposure device, and aerosol‐ and instillation‐infected mice simulated the clinical symptoms of moderate diffuse interstitial pneumonia. However, the transgenic mice exposed to aerosol MERS‐CoV developed disease and lung pathology progressions that more closely resembled those observed in humans.</p>
</sec>
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<journal-id journal-id-type="doi">10.1002/(ISSN)2576-2095</journal-id>
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<title-group><article-title>The characteristics of hDPP4 transgenic mice subjected to aerosol MERS coronavirus infection via an animal nose‐only exposure device</article-title>
<alt-title alt-title-type="left-running-head">HAO et al.</alt-title>
</title-group>
<contrib-group><contrib id="ame212088-cr-0001" contrib-type="author"><name><surname>Hao</surname>
<given-names>Xin‐yan</given-names>
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<xref ref-type="aff" rid="ame212088-aff-0001"><sup>1</sup>
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<contrib id="ame212088-cr-0002" contrib-type="author"><name><surname>Lv</surname>
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<xref ref-type="aff" rid="ame212088-aff-0001"><sup>1</sup>
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<xref ref-type="aff" rid="ame212088-aff-0001"><sup>1</sup>
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<contrib id="ame212088-cr-0005" contrib-type="author" corresp="yes"><name><surname>Gao</surname>
<given-names>Hong</given-names>
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<xref ref-type="aff" rid="ame212088-aff-0001"><sup>1</sup>
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<address><email>gaoh@cnilas.org</email>
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<aff id="ame212088-aff-0001"><label><sup>1</sup>
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<named-content content-type="organisation-division">Institute of Laboratory Animal Sciences</named-content>
<named-content content-type="organisation-division">Chinese Academy of Medical Sciences (CAMS) & Comparative Medicine Centre</named-content>
<named-content content-type="organisation-division">Peking Union Medical College (PUMC)</named-content>
<named-content content-type="organisation-division">Key Laboratory of Human Disease Comparative Medicine</named-content>
<named-content content-type="organisation-division">National Health Commission of China (NHC)</named-content>
<institution>Beijing Key Laboratory for Animal Models of Emerging and Reemerging Infections</institution>
<city>Beijing</city>
<country country="CN">China</country>
</aff>
<author-notes><corresp id="correspondenceTo"><label>*</label>
<bold>Correspondence</bold>
<break></break>
Hong Gao, Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences (CAMS) & Comparative Medicine Centre, Peking Union Medical College (PUMC), Key Laboratory of Human Disease Comparative Medicine, National Health Commission of China (NHC), Beijing Key Laboratory for Animal Models of Emerging and Reemerging Infections, Beijing, China.<break></break>
Email: <email>gaoh@cnilas.org</email>
<break></break>
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<pub-date pub-type="epub"><day>30</day>
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<volume>2</volume>
<issue>4</issue>
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<lpage>281</lpage>
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<month>7</month>
<year>2019</year>
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<date date-type="rev-recd"><day>12</day>
<month>9</month>
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<date date-type="accepted"><day>06</day>
<month>10</month>
<year>2019</year>
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<permissions><pmc-comment> © 2019 The Chinese Association for Laboratory Animal Sciences </pmc-comment>
<copyright-statement content-type="article-copyright">© 2019 The Authors. <italic>Animal Models and Experimental Medicine</italic>
published by John Wiley & Sons Australia, Ltd on behalf of The Chinese Association for Laboratory Animal Sciences</copyright-statement>
<license license-type="creativeCommonsBy-nc"><license-p>This is an open access article under the terms of the <ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by-nc/4.0/">http://creativecommons.org/licenses/by-nc/4.0/</ext-link>
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<self-uri content-type="pdf" xlink:href="file:AME2-2-269.pdf"></self-uri>
<abstract id="ame212088-abs-0001"><title>Abstract</title>
<sec id="ame212088-sec-0001"><title>Background</title>
<p>Middle East respiratory syndrome coronavirus (MERS‐CoV), which is not fully understood in regard to certain transmission routes and pathogenesis and lacks specific therapeutics and vaccines, poses a global threat to public health.</p>
</sec>
<sec id="ame212088-sec-0002"><title>Methods</title>
<p>To simulate the clinical aerosol transmission route, hDPP4 transgenic mice were infected with MERS‐CoV by an animal nose‐only exposure device and compared with instillation‐inoculated mice. The challenged mice were observed for 14 consecutive days and necropsied on days 3, 5, 7, and 9 to analyze viral load, histopathology, viral antigen distribution, and cytokines in tissues.</p>
</sec>
<sec id="ame212088-sec-0003"><title>Results</title>
<p>MERS‐CoV aerosol‐infected mice with an incubation period of 5‐7 days showed weight loss on days 7‐11, obvious lung lesions on day 7, high viral loads in the lungs on days 3‐9 and in the brain on days 7‐9, and 60% survival. MERS‐CoV instillation‐inoculated mice exhibited clinical signs on day 1, obvious lung lesions on days 3‐5, continuous weight loss, 0% survival by day 5, and high viral loads in the lungs and brain on days 3‐5. Viral antigen and high levels of proinflammatory cytokines and chemokines were detected in the aerosol and instillation groups. Disease, lung lesion, and viral replication progressions were slower in the MERS‐CoV aerosol‐infected mice than in the MERS‐CoV instillation‐inoculated mice.</p>
</sec>
<sec id="ame212088-sec-0004"><title>Conclusion</title>
<p>hDPP4 transgenic mice were successfully infected with MERS‐CoV aerosols via an animal nose‐only exposure device, and aerosol‐ and instillation‐infected mice simulated the clinical symptoms of moderate diffuse interstitial pneumonia. However, the transgenic mice exposed to aerosol MERS‐CoV developed disease and lung pathology progressions that more closely resembled those observed in humans.</p>
</sec>
</abstract>
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<kwd id="ame212088-kwd-0002">hDPP4 transgenic mice</kwd>
<kwd id="ame212088-kwd-0003">intranasal instillation</kwd>
<kwd id="ame212088-kwd-0004">MERS‐CoV aerosol infection</kwd>
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<funding-group><award-group id="funding-0001"><funding-source>National Science and Technology Major Projects of Infectious Disease</funding-source>
<award-id>2018ZX10734401‐011</award-id>
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<notes><p content-type="self-citation"><mixed-citation publication-type="journal" id="ame212088-cit-1001"><string-name><surname>Hao</surname>
<given-names>X</given-names>
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, <string-name><surname>Lv</surname>
<given-names>Q</given-names>
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, <string-name><surname>Li</surname>
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<given-names>Y</given-names>
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, <string-name><surname>Gao</surname>
<given-names>H</given-names>
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. <article-title>The characteristics of hDPP4 transgenic mice subjected to aerosol MERS coronavirus infection via an animal nose‐only exposure device</article-title>
. <source xml:lang="en">Anim Models Exp Med</source>
. <year>2019</year>
;<volume>2</volume>
:<fpage>269</fpage>
–<lpage>281</lpage>
. <pub-id pub-id-type="doi">10.1002/ame2.12088</pub-id>
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