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Intranasal infection of A\/J mice with the coronavirus murine hepatitis virus strain 1 (MHV-1) produced pulmonary pathological features of SARS. All MHV-1-infected A\/J mice developed progressive interstitial pneumonitis, including dense macrophage infiltrates, giant cells, and hyaline membranes, resulting in death of all animals. In contrast, other mouse strains developed only mild transitory disease. Infected A\/J mice had significantly higher cytokine levels, particularly macrophage chemoattractant protein 1 (MCP-1\/CCL-2), gamma interferon, and tumor necrosis factor alpha. Furthermore, FGL2\/fibroleukin mRNA transcripts and protein and fibrin deposits were markedly increased in the lungs of infected A\/J mice. These animals developed a less robust type I interferon response to MHV-1 infection than resistant C57BL\/6J mice, and treatment with recombinant beta interferon improved survival. This study describes a potentially useful small animal model of human SARS, defines its pathogenesis, and suggests treatment strategies.<\/jats:p>","DOI":"10.1128\/jvi.00747-06","type":"journal-article","created":{"date-parts":[[2006,10,15]],"date-time":"2006-10-15T06:42:36Z","timestamp":1160894556000},"page":"10382-10394","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":172,"title":["MurineHepatitis Virus Strain 1 Produces a Clinically Relevant Model of Severe Acute Respiratory Syndrome in A\/J Mice"],"prefix":"10.1128","volume":"80","author":[{"given":"Nadine","family":"De Albuquerque","sequence":"first","affiliation":[{"name":"Departments of Medicine"},{"name":"the Multi Organ Transplant Program"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ehtesham","family":"Baig","sequence":"additional","affiliation":[{"name":"University Health Network, University of Toronto, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuezhong","family":"Ma","sequence":"additional","affiliation":[{"name":"Departments of Medicine"},{"name":"the Multi Organ Transplant Program"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianhua","family":"Zhang","sequence":"additional","affiliation":[{"name":"Departments of Medicine"},{"name":"the Multi Organ Transplant Program"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"He","sequence":"additional","affiliation":[{"name":"Departments of Medicine"},{"name":"the Multi Organ Transplant Program"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Rowe","sequence":"additional","affiliation":[{"name":"Departments of Medicine"},{"name":"the Multi Organ Transplant Program"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marlena","family":"Habal","sequence":"additional","affiliation":[{"name":"Departments of Medicine"},{"name":"the Multi Organ Transplant Program"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingfeng","family":"Liu","sequence":"additional","affiliation":[{"name":"Departments of Medicine"},{"name":"the Multi Organ Transplant Program"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Itay","family":"Shalev","sequence":"additional","affiliation":[{"name":"Departments of Medicine"},{"name":"the Multi Organ Transplant Program"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory P.","family":"Downey","sequence":"additional","affiliation":[{"name":"Departments of Medicine"},{"name":"the Multi Organ Transplant Program"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reginald","family":"Gorczynski","sequence":"additional","affiliation":[{"name":"Surgery"},{"name":"the Multi Organ Transplant Program"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jagdish","family":"Butany","sequence":"additional","affiliation":[{"name":"Pathology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julian","family":"Leibowitz","sequence":"additional","affiliation":[{"name":"Department of Microbial and Molecular Pathogenesis, Texas A&amp;M University System-HSC, College Station, Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan R.","family":"Weiss","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University of Pennsylvania, Philadelphia, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian D.","family":"McGilvray","sequence":"additional","affiliation":[{"name":"Surgery"},{"name":"the Multi Organ Transplant Program"},{"name":"University Health Network, University of Toronto, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. 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