{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T12:52:09Z","timestamp":1790427129414,"version":"4.1.0"},"reference-count":38,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2015,10,14]],"date-time":"2015-10-14T00:00:00Z","timestamp":1444780800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology"],"published-print":{"date-parts":[[2016,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>To study bacterial co\u2010infection following 1918 <jats:styled-content style=\"fixed-case\">H1N1<\/jats:styled-content> influenza virus infection, mice were inoculated with the 1918 influenza virus, followed by <jats:italic>Streptococcus pneumoniae<\/jats:italic> (<jats:styled-content style=\"fixed-case\">SP<\/jats:styled-content>) 72\u2009h later. Co\u2010infected mice exhibited markedly more severe disease, shortened survival time and more severe lung pathology, including widespread thrombi. Transcriptional profiling revealed activation of coagulation only in co\u2010infected mice, consistent with the extensive thrombogenesis observed. Immunohistochemistry showed extensive expression of tissue factor (<jats:styled-content style=\"fixed-case\">F3<\/jats:styled-content>) and prominent deposition of neutrophil elastase on endothelial and epithelial cells in co\u2010infected mice. Lung sections of <jats:styled-content style=\"fixed-case\">SP<\/jats:styled-content>\u2010positive 1918 autopsy cases showed extensive thrombi and prominent staining for <jats:styled-content style=\"fixed-case\">F3<\/jats:styled-content> in alveolar macrophages, monocytes, neutrophils, endothelial and epithelial cells, in contrast to co\u2010infection\u2010positive 2009 pandemic <jats:styled-content style=\"fixed-case\">H1N1<\/jats:styled-content> autopsy cases. This study reveals that a distinctive feature of 1918 influenza virus and <jats:styled-content style=\"fixed-case\">SP<\/jats:styled-content> co\u2010infection in mice and humans is extensive expression of tissue factor and activation of the extrinsic coagulation pathway leading to widespread pulmonary thrombosis. Copyright \u00a9 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/path.4638","type":"journal-article","created":{"date-parts":[[2015,9,18]],"date-time":"2015-09-18T05:50:46Z","timestamp":1442555446000},"page":"85-97","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":46,"title":["1918 pandemic influenza virus and <i>Streptococcus pneumoniae<\/i> co\u2010infection results in activation of coagulation and widespread pulmonary thrombosis in mice and humans"],"prefix":"10.1002","volume":"238","author":[{"given":"Kathie\u2010Anne","family":"Walters","sequence":"first","affiliation":[{"name":"Institute for Systems Biology  Seattle WA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felice","family":"D'Agnillo","sequence":"additional","affiliation":[{"name":"Laboratory of Biochemistry and Vascular Biology, Division of Hematology Research and Review, Center for Biologics Evaluation and Research, Office of Blood 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