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1918 pandemic influenza virus and Streptococcus pneumoniae co‐infection results in activation of coagulation and widespread pulmonary thrombosis in mice and humans
Author(s) -
Walters KathieAnne,
D'Agnillo Felice,
Sheng ZongMei,
Kindrachuk Jason,
Schwartzman Louis M,
Kuestner Rolf E,
Chertow Daniel S,
Golding Basil T,
Taubenberger Jeffery K,
Kash John C
Publication year - 2016
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/path.4638
Subject(s) - streptococcus pneumoniae , tissue factor , influenza a virus , virus , lung , immunology , biology , immunohistochemistry , pathology , coagulation , autopsy , virology , medicine , microbiology and biotechnology , antibiotics , psychiatry
To study bacterial co‐infection following 1918 H1N1 influenza virus infection, mice were inoculated with the 1918 influenza virus, followed by Streptococcus pneumoniae ( SP ) 72 h later. Co‐infected 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‐infected mice, consistent with the extensive thrombogenesis observed. Immunohistochemistry showed extensive expression of tissue factor ( F3 ) and prominent deposition of neutrophil elastase on endothelial and epithelial cells in co‐infected mice. Lung sections of SP ‐positive 1918 autopsy cases showed extensive thrombi and prominent staining for F3 in alveolar macrophages, monocytes, neutrophils, endothelial and epithelial cells, in contrast to co‐infection‐positive 2009 pandemic H1N1 autopsy cases. This study reveals that a distinctive feature of 1918 influenza virus and SP co‐infection in mice and humans is extensive expression of tissue factor and activation of the extrinsic coagulation pathway leading to widespread pulmonary thrombosis. Copyright © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.