{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T22:47:39Z","timestamp":1778885259572,"version":"3.51.4"},"reference-count":73,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2017,8,4]],"date-time":"2017-08-04T00:00:00Z","timestamp":1501804800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2017,8,4]],"date-time":"2017-08-04T00:00:00Z","timestamp":1501804800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>New influenza A viruses that emerge frequently elicit composite inflammatory responses to both infection and structural damage of alveolar-capillary barrier cells that hinders regeneration of respiratory function. The host factors that relinquish restoration of lung health to enduring lung injury are insufficiently understood. Here, we investigated the role of endophilin B2 (B2) in susceptibility to severe influenza infection. WT and B2-deficient mice were infected with H1N1 PR8 by intranasal administration and course of influenza pneumonia, inflammatory, and tissue responses were monitored over time. Disruption of B2 enhanced recovery from severe influenza infection as indicated by swift body weight recovery and significantly better survival of endophilin B2-deficient mice compared to WT mice. Compared to WT mice, the B2-deficient lungs exhibited induction of genes that express surfactant proteins, ABCA3, GM-CSF, podoplanin, and caveolin mRNA after 7 days, temporal induction of CCAAT\/enhancer binding protein CEBP\u03b1, \u03b2, and \u03b4 mRNAs 3\u201314 days after infection, and differences in alveolar extracellular matrix integrity and respiratory mechanics. Flow cytometry and gene expression studies demonstrated robust recovery of alveolar macrophages and recruitment of CD4+ lymphocytes in B2-deficient lungs. Targeting of endophilin B2 alleviates adverse effects of IAV infection on respiratory and immune cells enabling restoration of alveolar homeostasis.<\/jats:p>","DOI":"10.1038\/s41598-017-07724-5","type":"journal-article","created":{"date-parts":[[2017,7,31]],"date-time":"2017-07-31T08:35:49Z","timestamp":1501490149000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["SH3GLB2\/endophilin B2 regulates lung homeostasis and recovery from severe influenza A virus infection"],"prefix":"10.1038","volume":"7","author":[{"given":"Kristin K.","family":"Fino","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Linlin","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7083-8915","authenticated-orcid":false,"given":"Patricia","family":"Silveyra","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sanmei","family":"Hu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Todd M.","family":"Umstead","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susan","family":"DiAngelo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"E. Scott","family":"Halstead","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Timothy K.","family":"Cooper","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Abraham","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshinori","family":"Takahashi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhixiang","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hong Gang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zissis C.","family":"Chroneos","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2017,8,4]]},"reference":[{"key":"7724_CR1","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1146\/annurev.pathmechdis.3.121806.154316","volume":"3","author":"JK Taubenberger","year":"2008","unstructured":"Taubenberger, J. K. & Morens, D. M. The pathology of influenza virus infections. Annual review of pathology \n                           3, 499\u2013522, doi:10.1146\/annurev.pathmechdis.3.121806.154316 (2008).","journal-title":"Annual review of pathology"},{"key":"7724_CR2","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1093\/femsre\/fuv039","volume":"40","author":"M Richard","year":"2016","unstructured":"Richard, M. & Fouchier, R. A. Influenza A virus transmission via respiratory aerosols or droplets as it relates to pandemic potential. FEMS microbiology reviews \n                           40, 68\u201385, doi:10.1093\/femsre\/fuv039 (2016).","journal-title":"FEMS microbiology reviews"},{"key":"7724_CR3","doi-asserted-by":"publisher","first-page":"02016","DOI":"10.1152\/ajplung.00339.2016","volume":"00339","author":"PS Woods","year":"2016","unstructured":"Woods, P. S. et al. Lethal H1N1 Influenza A Virus Infection Alters the Murine Alveolar Type II Cell Surfactant Lipidome. Am J Physiol Lung Cell Mol Physiol, ajplung \n                           00339, 02016, doi:10.1152\/ajplung.00339.2016 (2016).","journal-title":"Am J Physiol Lung Cell Mol Physiol, ajplung"},{"key":"7724_CR4","doi-asserted-by":"publisher","first-page":"954","DOI":"10.1183\/13993003.01282-2015","volume":"47","author":"KR Short","year":"2016","unstructured":"Short, K. R. et al. Influenza virus damages the alveolar barrier by disrupting epithelial cell tight junctions. Eur Respir J \n                           47, 954\u2013966, doi:10.1183\/13993003.01282-2015 (2016).","journal-title":"Eur Respir J"},{"key":"7724_CR5","doi-asserted-by":"publisher","first-page":"L481","DOI":"10.1152\/ajplung.00343.2012","volume":"304","author":"CJ Sanders","year":"2013","unstructured":"Sanders, C. J. et al. Compromised respiratory function in lethal influenza infection is characterized by the depletion of type I alveolar epithelial cells beyond threshold levels. 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