{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T17:52:04Z","timestamp":1791136324254,"version":"4.1.0"},"reference-count":29,"publisher":"American Society for Microbiology","issue":"14","license":[{"start":{"date-parts":[[2014,7,15]],"date-time":"2014-07-15T00:00:00Z","timestamp":1405382400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2014,7,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Influenza A viruses recruit components of the nuclear import pathway to enter the host cell nucleus and promote viral replication. Here, we analyzed the role of the nuclear import factor importin-\u03b17 in H1N1 influenza virus pulmonary tropism by using various\n            <jats:italic>ex vivo<\/jats:italic>\n            imaging techniques (magnetic resonance imaging, confocal laser scanning microscopy, and correlative light-electron microscopy). We infected importin-\u03b17 gene-deficient (\u03b17\n            <jats:sup>\u2212\/\u2212<\/jats:sup>\n            ) mice with a recombinant H1N1 influenza virus and compared the\n            <jats:italic>in vivo<\/jats:italic>\n            viral kinetics with those in wild-type (WT) mice. In WT mice, influenza virus replication in the bronchial and alveolar epithelium already occurred a few days after infection. Accordingly, extensive mononuclear infiltration and alveolar destruction were present in the lungs of infected WT mice, followed by 100% lethality. Conversely, in \u03b17\n            <jats:sup>\u2212\/\u2212<\/jats:sup>\n            mice, virus replication was restricted mostly to the bronchial epithelium with marginal alveolar infection, resulting in significantly reduced lung damage and enhanced animal survival. To investigate the host immune response during alveolar virus replication, we studied the role of primary macrophages in virus propagation and clearance. The ability of macrophages to support or clear the virus infection, as well as the host cellular immune responses, did not significantly differ between WT and \u03b17\n            <jats:sup>\u2212\/\u2212<\/jats:sup>\n            mice. However, cytokine and chemokine responses were generally elevated in WT mice, likely reflective of increased viral replication in the lung. In summary, these data show that a cellular factor, importin-\u03b17, is required for enhanced virus replication in the alveolar epithelium, resulting in elevated cytokine and chemokine levels, extensive mononuclear infiltration, and thus, severe pneumonia and enhanced virulence in mice.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>IMPORTANCE<\/jats:bold>\n            Influenza A viruses are respiratory pathogens that may cause pneumonia in humans. Viral infection and replication in the alveoli of the respiratory tract are believed to be crucial for the development of the acute respiratory distress syndrome associated with fatal outcomes in influenza virus-infected patients. Here, we report the requirement of a cellular factor, importin-\u03b17, for efficient virus replication in the alveolar epithelium of mice. Using complementary\n            <jats:italic>ex vivo<\/jats:italic>\n            imaging approaches, we show that influenza virus replication is restricted to the bronchial epithelium, followed by enhanced survival in importin-\u03b17-deficient mice. In contrast, the presence of this gene results in enhanced virus replication in the alveoli, elevated cytokine and chemokine responses, mononuclear infiltration, alveolar destruction, and 100% lethality in wild-type mice. Taken together, our results show that importin-\u03b17 is particularly required for virus replication in the alveolar epithelium in association with severe pneumonia and death in mice.\n          <\/jats:p>","DOI":"10.1128\/jvi.00270-14","type":"journal-article","created":{"date-parts":[[2014,5,15]],"date-time":"2014-05-15T01:56:52Z","timestamp":1400119012000},"page":"8166-8179","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":28,"title":["Importin-\u03b17 Is Required for Enhanced Influenza A Virus Replication in the Alveolar Epithelium and Severe Lung Damage in Mice"],"prefix":"10.1128","volume":"88","author":[{"given":"Patricia","family":"Resa-Infante","sequence":"first","affiliation":[{"name":"Heinrich Pette Institute, Leibniz Institute for Experimental Virology, Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ren\u00e9","family":"Thieme","sequence":"additional","affiliation":[{"name":"Laboratory for Experimental Fetomaternal Medicine, Department of Obstetrics and Fetal Medicine, University Medical Center Hamburg, Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Ernst","sequence":"additional","affiliation":[{"name":"Diagnostic and Interventional Radiology Department and Clinic, University Hospital Hamburg-Eppendorf, Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petra C.","family":"Arck","sequence":"additional","affiliation":[{"name":"Laboratory for Experimental Fetomaternal Medicine, Department of Obstetrics and Fetal Medicine, University Medical Center Hamburg, Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harald","family":"Ittrich","sequence":"additional","affiliation":[{"name":"Diagnostic and Interventional Radiology Department and Clinic, University Hospital Hamburg-Eppendorf, Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rudolph","family":"Reimer","sequence":"additional","affiliation":[{"name":"Heinrich Pette Institute, Leibniz Institute for Experimental Virology, Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G\u00fclsah","family":"Gabriel","sequence":"additional","affiliation":[{"name":"Heinrich Pette Institute, Leibniz Institute for Experimental Virology, Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1002\/bies.201000118"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/bies.201200138"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrm2928"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.0040011"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1002488"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms1158"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri3166"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(13)70286-X"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0914994107"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1002\/9780471729259.mc15g04s29"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0018310"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2009.090339"},{"key":"e_1_3_3_14_2","first-page":"608","article-title":"Galloylglucoses of low molecular weight as mordant in electron microscopy. I","volume":"70","author":"Simionescu N","year":"1976","unstructured":"SimionescuNSimionescuM. 1976. Galloylglucoses of low molecular weight as mordant in electron microscopy. I. Procedure, and evidence for mordanting effect. J. Cell Biol. 70:608\u2013621.","journal-title":"Procedure, and evidence for mordanting effect. J. Cell Biol."},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1002\/0471142735.im1401s83"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01210-07"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.171.6.3128"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02682-12"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000115"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.2217\/fvl.12.11"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1002099"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jis523"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2008.03.054"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.E09-05-0361"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.3109\/00365521.2011.568516"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20130071"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.72.6.4825-4831.1998"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2012.05.005"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncb1521"},{"key":"e_1_3_3_30_2","first-page":"493","article-title":"A simple method of estimating fifty percent endpoints","volume":"27","author":"Reed L","year":"1938","unstructured":"ReedLMuenchH. 1938. A simple method of estimating fifty percent endpoints. Am. J. Hyg. 27:493\u2013497.","journal-title":"Am. J. Hyg."}],"container-title":["Journal of Virology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/JVI.00270-14","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/JVI.00270-14","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,5]],"date-time":"2022-03-05T15:38:31Z","timestamp":1646494711000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/JVI.00270-14"}},"subtitle":[],"editor":[{"given":"A.","family":"Garc\u00eda-Sastre","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2014,7,15]]},"references-count":29,"journal-issue":{"issue":"14","published-print":{"date-parts":[[2014,7,15]]}},"alternative-id":["10.1128\/JVI.00270-14"],"URL":"https:\/\/doi.org\/10.1128\/jvi.00270-14","relation":{},"ISSN":["0022-538X","1098-5514"],"issn-type":[{"value":"0022-538X","type":"print"},{"value":"1098-5514","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,7,15]]},"assertion":[{"value":"2014-01-29","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2014-05-05","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2014-06-20","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}