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We compared the temporal transcriptional responses of human dendritic cells (DC) to infection with two pandemic (A\/Brevig Mission\/1\/1918, A\/California\/4\/2009) and two seasonal (A\/New Caledonia\/20\/1999, A\/Texas\/36\/1991) H1N1 influenza viruses. Strain-specific response differences included stronger activation of NF-\u03baB following infection with A\/New Caledonia\/20\/1999 and a unique cluster of genes expressed following infection with A\/Brevig Mission\/1\/1918. A common antiviral program showing strain-specific timing was identified in the early DC response and found to correspond with reported transcript changes in blood during symptomatic human influenza virus infection. Comparison of the global responses to the seasonal and pandemic strains showed that a dramatic divergence occurred after 4 h, with only the seasonal strains inducing widespread mRNA loss.<\/jats:p><jats:p><jats:bold>IMPORTANCE<\/jats:bold>Continuously evolving influenza viruses present a global threat to human health; however, these host responses display strain-dependent differences that are incompletely understood. Thus, we conducted a detailed comparative study assessing the immune responses of human DC to infection with two pandemic and two seasonal H1N1 influenza strains. We identified in the immune response to viral infection both common and strain-specific features. Among the stain-specific elements were a time shift of the interferon-stimulated gene response, selective induction of NF-\u03baB signaling by one of the seasonal strains, and massive RNA degradation as early as 4 h postinfection by the seasonal, but not the pandemic, viruses. These findings illuminate new aspects of the distinct differences in the immune responses to pandemic and seasonal influenza viruses.<\/jats:p>","DOI":"10.1128\/jvi.01523-15","type":"journal-article","created":{"date-parts":[[2015,7,30]],"date-time":"2015-07-30T02:55:30Z","timestamp":1438224930000},"page":"10190-10205","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":28,"title":["Human Dendritic Cell Response Signatures Distinguish 1918, Pandemic, and Seasonal H1N1 Influenza Viruses"],"prefix":"10.1128","volume":"89","author":[{"given":"Boris M.","family":"Hartmann","sequence":"first","affiliation":[{"name":"Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, New York, USA"},{"name":"Center for Translational Systems Biology, Icahn School of Medicine at Mount Sinai, New York, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juilee","family":"Thakar","sequence":"additional","affiliation":[{"name":"Department of Pathology, Yale School of Medicine, New Haven, Connecticut, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Randy A.","family":"Albrecht","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA"},{"name":"Global Health &amp; 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