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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Coronavirus MHV-A59 infects the lung and causes severe pneumonia in C57BL/6 mice</title><author><name sortKey="Yang, Zhangsheng" sort="Yang, Zhangsheng" uniqKey="Yang Z" first="Zhangsheng" last="Yang">Zhangsheng Yang</name><affiliation><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="GRID">grid.9227.e</institution-id><institution-id institution-id-type="ISNI">0000000119573309</institution-id><institution>Key Laboratory of Infection and Immunity (CASKLII), Institute of Biophysics,</institution><institution>Chinese Academy of Sciences,</institution></institution-wrap>15 Datun Road, Chaoyang District, Beijing, 100101 China</nlm:aff></affiliation></author><author><name sortKey="Du, Jun" sort="Du, Jun" uniqKey="Du J" first="Jun" last="Du">Jun Du</name><affiliation><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="GRID">grid.163032.5</institution-id><institution-id institution-id-type="ISNI">0000000417602008</institution-id><institution>Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Institute of Biotechnology,</institution><institution>Shanxi University,</institution></institution-wrap>Taiyuan, 030006 China</nlm:aff></affiliation></author><author><name sortKey="Chen, Gang" sort="Chen, Gang" uniqKey="Chen G" first="Gang" last="Chen">Gang Chen</name><affiliation><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="GRID">grid.9227.e</institution-id><institution-id institution-id-type="ISNI">0000000119573309</institution-id><institution>Key Laboratory of Infection and Immunity (CASKLII), Institute of Biophysics,</institution><institution>Chinese Academy of Sciences,</institution></institution-wrap>15 Datun Road, Chaoyang District, Beijing, 100101 China</nlm:aff></affiliation></author><author><name sortKey="Zhao, Jie" sort="Zhao, Jie" uniqKey="Zhao J" first="Jie" last="Zhao">Jie Zhao</name><affiliation><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="GRID">grid.9227.e</institution-id><institution-id institution-id-type="ISNI">0000000119573309</institution-id><institution>Key Laboratory of Infection and Immunity (CASKLII), Institute of Biophysics,</institution><institution>Chinese Academy of Sciences,</institution></institution-wrap>15 Datun Road, Chaoyang District, Beijing, 100101 China</nlm:aff></affiliation></author><author><name sortKey="Yang, Xuanming" sort="Yang, Xuanming" uniqKey="Yang X" first="Xuanming" last="Yang">Xuanming Yang</name><affiliation><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="GRID">grid.9227.e</institution-id><institution-id institution-id-type="ISNI">0000000119573309</institution-id><institution>Key Laboratory of Infection and Immunity (CASKLII), Institute of Biophysics,</institution><institution>Chinese Academy of Sciences,</institution></institution-wrap>15 Datun Road, Chaoyang District, Beijing, 100101 China</nlm:aff></affiliation></author><author><name sortKey="Su, Lishan" sort="Su, Lishan" uniqKey="Su L" first="Lishan" last="Su">Lishan Su</name><affiliation><nlm:aff id="Aff3"><institution-wrap><institution-id institution-id-type="GRID">grid.10698.36</institution-id><institution-id institution-id-type="ISNI">0000000122483208</institution-id><institution>Department of Microbiology and Immunology and Lineberger Comprehensive Cancer Center,</institution><institution>University of North Carolina at Chapel Hill School of Medicine,</institution></institution-wrap>Chapel Hill, NC 27599-7295 USA</nlm:aff></affiliation></author><author><name sortKey="Cheng, Genhong" sort="Cheng, Genhong" uniqKey="Cheng G" first="Genhong" last="Cheng">Genhong Cheng</name><affiliation><nlm:aff id="Aff4"><institution-wrap><institution-id institution-id-type="GRID">grid.19006.3e</institution-id><institution-id institution-id-type="ISNI">0000000096326718</institution-id><institution>Department of Microbiology, Immunology and Molecular Genetics,</institution><institution>University of California,</institution></institution-wrap>Los Angeles, CA 90095 USA</nlm:aff></affiliation></author><author><name sortKey="Tang, Hong" sort="Tang, Hong" uniqKey="Tang H" first="Hong" last="Tang">Hong Tang</name><affiliation><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="GRID">grid.9227.e</institution-id><institution-id institution-id-type="ISNI">0000000119573309</institution-id><institution>Key Laboratory of Infection and Immunity (CASKLII), Institute of Biophysics,</institution><institution>Chinese Academy of Sciences,</institution></institution-wrap>15 Datun Road, Chaoyang District, Beijing, 100101 China</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">25547683</idno><idno type="pmc">7090691</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7090691</idno><idno type="RBID">PMC:7090691</idno><idno type="doi">10.1007/s12250-014-3530-y</idno><date when="2014">2014</date><idno type="wicri:Area/Pmc/Corpus">000486</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000486</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Coronavirus MHV-A59 infects the lung and causes severe pneumonia in C57BL/6 mice</title><author><name sortKey="Yang, Zhangsheng" sort="Yang, Zhangsheng" uniqKey="Yang Z" first="Zhangsheng" last="Yang">Zhangsheng Yang</name><affiliation><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="GRID">grid.9227.e</institution-id><institution-id institution-id-type="ISNI">0000000119573309</institution-id><institution>Key Laboratory of Infection and Immunity (CASKLII), Institute of Biophysics,</institution><institution>Chinese Academy of Sciences,</institution></institution-wrap>15 Datun Road, Chaoyang District, Beijing, 100101 China</nlm:aff></affiliation></author><author><name sortKey="Du, Jun" sort="Du, Jun" uniqKey="Du J" first="Jun" last="Du">Jun Du</name><affiliation><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="GRID">grid.163032.5</institution-id><institution-id institution-id-type="ISNI">0000000417602008</institution-id><institution>Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Institute of Biotechnology,</institution><institution>Shanxi University,</institution></institution-wrap>Taiyuan, 030006 China</nlm:aff></affiliation></author><author><name sortKey="Chen, Gang" sort="Chen, Gang" uniqKey="Chen G" first="Gang" last="Chen">Gang Chen</name><affiliation><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="GRID">grid.9227.e</institution-id><institution-id institution-id-type="ISNI">0000000119573309</institution-id><institution>Key Laboratory of Infection and Immunity (CASKLII), Institute of Biophysics,</institution><institution>Chinese Academy of Sciences,</institution></institution-wrap>15 Datun Road, Chaoyang District, Beijing, 100101 China</nlm:aff></affiliation></author><author><name sortKey="Zhao, Jie" sort="Zhao, Jie" uniqKey="Zhao J" first="Jie" last="Zhao">Jie Zhao</name><affiliation><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="GRID">grid.9227.e</institution-id><institution-id institution-id-type="ISNI">0000000119573309</institution-id><institution>Key Laboratory of Infection and Immunity (CASKLII), Institute of Biophysics,</institution><institution>Chinese Academy of Sciences,</institution></institution-wrap>15 Datun Road, Chaoyang District, Beijing, 100101 China</nlm:aff></affiliation></author><author><name sortKey="Yang, Xuanming" sort="Yang, Xuanming" uniqKey="Yang X" first="Xuanming" last="Yang">Xuanming Yang</name><affiliation><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="GRID">grid.9227.e</institution-id><institution-id institution-id-type="ISNI">0000000119573309</institution-id><institution>Key Laboratory of Infection and Immunity (CASKLII), Institute of Biophysics,</institution><institution>Chinese Academy of Sciences,</institution></institution-wrap>15 Datun Road, Chaoyang District, Beijing, 100101 China</nlm:aff></affiliation></author><author><name sortKey="Su, Lishan" sort="Su, Lishan" uniqKey="Su L" first="Lishan" last="Su">Lishan Su</name><affiliation><nlm:aff id="Aff3"><institution-wrap><institution-id institution-id-type="GRID">grid.10698.36</institution-id><institution-id institution-id-type="ISNI">0000000122483208</institution-id><institution>Department of Microbiology and Immunology and Lineberger Comprehensive Cancer Center,</institution><institution>University of North Carolina at Chapel Hill School of Medicine,</institution></institution-wrap>Chapel Hill, NC 27599-7295 USA</nlm:aff></affiliation></author><author><name sortKey="Cheng, Genhong" sort="Cheng, Genhong" uniqKey="Cheng G" first="Genhong" last="Cheng">Genhong Cheng</name><affiliation><nlm:aff id="Aff4"><institution-wrap><institution-id institution-id-type="GRID">grid.19006.3e</institution-id><institution-id institution-id-type="ISNI">0000000096326718</institution-id><institution>Department of Microbiology, Immunology and Molecular Genetics,</institution><institution>University of California,</institution></institution-wrap>Los Angeles, CA 90095 USA</nlm:aff></affiliation></author><author><name sortKey="Tang, Hong" sort="Tang, Hong" uniqKey="Tang H" first="Hong" last="Tang">Hong Tang</name><affiliation><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="GRID">grid.9227.e</institution-id><institution-id institution-id-type="ISNI">0000000119573309</institution-id><institution>Key Laboratory of Infection and Immunity (CASKLII), Institute of Biophysics,</institution><institution>Chinese Academy of Sciences,</institution></institution-wrap>15 Datun Road, Chaoyang District, Beijing, 100101 China</nlm:aff></affiliation></author></analytic><series><title level="j">Virologica Sinica</title><idno type="ISSN">1674-0769</idno><idno type="eISSN">1995-820X</idno><imprint><date when="2014">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>It remains challenging to develop animal models of lung infection and severe pneumonia by severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome cornavirus (MERS-CoV) without high level of containment. This inevitably hinders understanding of virushost interaction and development of appropriate countermeasures. Here we report that intranasal inoculation of sublethal doses of murine coronavirus mouse hepatitis virus A-59 (MHV-A59), a hepatic and neuronal tropic coronavirus, can induce acute pneumonia and severe lung injuries in C57BL/6 mice. Inflammatory leukocyte infiltrations, hemorrhages and fibrosis of alveolar walls can be observed 2–11 days after MHV-A59 infection. This pathological manifestation is associated with dramatical elevation of tissue IP-10 and IFN-γ and moderate increase of TNF-α and IL-1β, but inability of anti-viral type I interferon response. These results suggest that intranasal infection of MHV-A59 would serve as a surrogate mouse model of acute respiratory distress syndrome by SARS-CoV and MERS-CoV infections.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Aparicio, J L" uniqKey="Aparicio J">J L Aparicio</name></author><author><name sortKey="Pena, C" uniqKey="Pena C">C Pena</name></author><author><name sortKey="Retegui, L A" uniqKey="Retegui L">L A Retegui</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Barthold, S W" uniqKey="Barthold S">S W Barthold</name></author><author><name sortKey="Smith, A L" uniqKey="Smith A">A L Smith</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Biddison, W E" uniqKey="Biddison W">W E Biddison</name></author><author><name sortKey="Cruikshank, W W" uniqKey="Cruikshank W">W W Cruikshank</name></author><author><name sortKey="Center, D M" uniqKey="Center D">D M 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<front><journal-meta><journal-id journal-id-type="nlm-ta">Virol Sin</journal-id><journal-id journal-id-type="iso-abbrev">Virol Sin</journal-id><journal-title-group><journal-title>Virologica Sinica</journal-title></journal-title-group><issn pub-type="ppub">1674-0769</issn><issn pub-type="epub">1995-820X</issn><publisher><publisher-name>Wuhan Institute of Virology, CAS</publisher-name><publisher-loc>Heidelberg</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">25547683</article-id><article-id pub-id-type="pmc">7090691</article-id><article-id pub-id-type="publisher-id">3530</article-id><article-id pub-id-type="doi">10.1007/s12250-014-3530-y</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group></article-categories><title-group><article-title>Coronavirus MHV-A59 infects the lung and causes severe pneumonia in C57BL/6 mice</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Yang</surname><given-names>Zhangsheng</given-names></name><xref ref-type="aff" rid="Aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Du</surname><given-names>Jun</given-names></name><xref ref-type="aff" rid="Aff2">2</xref></contrib><contrib contrib-type="author"><name><surname>Chen</surname><given-names>Gang</given-names></name><xref ref-type="aff" rid="Aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Zhao</surname><given-names>Jie</given-names></name><xref ref-type="aff" rid="Aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Yang</surname><given-names>Xuanming</given-names></name><xref ref-type="aff" rid="Aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Su</surname><given-names>Lishan</given-names></name><xref ref-type="aff" rid="Aff3">3</xref></contrib><contrib contrib-type="author"><name><surname>Cheng</surname><given-names>Genhong</given-names></name><xref ref-type="aff" rid="Aff4">4</xref></contrib><contrib contrib-type="author" corresp="yes"><name><surname>Tang</surname><given-names>Hong</given-names></name><address><phone>+86-27-87197727</phone><email>tanghong@moon.ibp.ac.cn</email></address><xref ref-type="aff" rid="Aff1">1</xref></contrib><aff id="Aff1"><label>1</label><institution-wrap><institution-id institution-id-type="GRID">grid.9227.e</institution-id><institution-id institution-id-type="ISNI">0000000119573309</institution-id><institution>Key Laboratory of Infection and Immunity (CASKLII), Institute of Biophysics,</institution><institution>Chinese Academy of Sciences,</institution></institution-wrap>15 Datun Road, Chaoyang District, Beijing, 100101 China</aff><aff id="Aff2"><label>2</label><institution-wrap><institution-id institution-id-type="GRID">grid.163032.5</institution-id><institution-id institution-id-type="ISNI">0000000417602008</institution-id><institution>Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Institute of Biotechnology,</institution><institution>Shanxi University,</institution></institution-wrap>Taiyuan, 030006 China</aff><aff id="Aff3"><label>3</label><institution-wrap><institution-id institution-id-type="GRID">grid.10698.36</institution-id><institution-id institution-id-type="ISNI">0000000122483208</institution-id><institution>Department of Microbiology and Immunology and Lineberger Comprehensive Cancer Center,</institution><institution>University of North Carolina at Chapel Hill School of Medicine,</institution></institution-wrap>Chapel Hill, NC 27599-7295 USA</aff><aff id="Aff4"><label>4</label><institution-wrap><institution-id institution-id-type="GRID">grid.19006.3e</institution-id><institution-id institution-id-type="ISNI">0000000096326718</institution-id><institution>Department of Microbiology, Immunology and Molecular Genetics,</institution><institution>University of California,</institution></institution-wrap>Los Angeles, CA 90095 USA</aff></contrib-group><pub-date pub-type="epub"><day>22</day><month>12</month><year>2014</year></pub-date><pub-date pub-type="collection"><month>12</month><year>2014</year></pub-date><volume>29</volume><issue>6</issue><fpage>393</fpage><lpage>402</lpage><history><date date-type="received"><day>2</day><month>11</month><year>2014</year></date><date date-type="accepted"><day>10</day><month>12</month><year>2014</year></date></history><permissions><copyright-statement>© Wuhan Institute of Virology, CAS and Springer-Verlag Berlin Heidelberg 2014</copyright-statement><license><license-p>This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.</license-p></license></permissions><abstract id="Abs1"><p>It remains challenging to develop animal models of lung infection and severe pneumonia by severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome cornavirus (MERS-CoV) without high level of containment. This inevitably hinders understanding of virushost interaction and development of appropriate countermeasures. Here we report that intranasal inoculation of sublethal doses of murine coronavirus mouse hepatitis virus A-59 (MHV-A59), a hepatic and neuronal tropic coronavirus, can induce acute pneumonia and severe lung injuries in C57BL/6 mice. Inflammatory leukocyte infiltrations, hemorrhages and fibrosis of alveolar walls can be observed 2–11 days after MHV-A59 infection. This pathological manifestation is associated with dramatical elevation of tissue IP-10 and IFN-γ and moderate increase of TNF-α and IL-1β, but inability of anti-viral type I interferon response. These results suggest that intranasal infection of MHV-A59 would serve as a surrogate mouse model of acute respiratory distress syndrome by SARS-CoV and MERS-CoV infections.</p></abstract><kwd-group xml:lang="en"><title>Keywords</title><kwd>coronavirus</kwd><kwd>MHV-A59</kwd><kwd>pneumonia</kwd><kwd>inflammation</kwd><kwd>cytokine</kwd></kwd-group><custom-meta-group><custom-meta><meta-name>issue-copyright-statement</meta-name><meta-value>© Wuhan Institute of Virology, CAS and Springer-Verlag Berlin Heidelberg 2014</meta-value></custom-meta></custom-meta-group></article-meta></front><back><ref-list id="Bib1"><title>References</title><ref id="CR1"><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Aparicio</surname><given-names>J L</given-names></name><name><surname>Pena</surname><given-names>C</given-names></name><name><surname>Retegui</surname><given-names>L A</given-names></name></person-group><article-title>Autoimmune hepatitis-like 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