title: Human Dendritic Cell Response Signatures Distinguish 1918, Pandemic, and Seasonal H1N1 Influenza Viruses.
abstract: Influenza viruses continue to present global threats to human health. Antigenic drift and shift, genetic reassortment, and cross-species transmission generate new strains with differences in epidemiology and clinical severity. 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-κB 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.
  
  
  OBJECTIVE
  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-κB 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.
authors.affiliation: Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, New York, USA Center for Translational Systems Biology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Boris M
authors.initials: BM
authors.lastname: Hartmann
authors.affiliation: Department of Pathology, Yale School of Medicine, New Haven, Connecticut, USA.
authors.forename: Juilee
authors.initials: J
authors.lastname: Thakar
authors.affiliation: Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA Global Health & Emerging Pathogens Institute at Icahn School of Medicine, New York, New York, USA.
authors.forename: Randy A
authors.initials: RA
authors.lastname: Albrecht
authors.affiliation: Interdepartmental Program in Computational Biology and Bioinformatics, Yale University, New Haven, Connecticut, USA.
authors.forename: Stefan
authors.initials: S
authors.lastname: Avey
authors.affiliation: Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, New York, USA Center for Translational Systems Biology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Elena
authors.initials: E
authors.lastname: Zaslavsky
authors.affiliation: Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Nada
authors.initials: N
authors.lastname: Marjanovic
authors.affiliation: Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Maria
authors.initials: M
authors.lastname: Chikina
authors.affiliation: Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Miguel
authors.initials: M
authors.lastname: Fribourg
authors.affiliation: Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, New York, USA Center for Translational Systems Biology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Fernand
authors.initials: F
authors.lastname: Hayot
authors.affiliation: Department of Microbiology and Molecular Medicine, University of Geneva, Geneva, Switzerland.
authors.forename: Mirco
authors.initials: M
authors.lastname: Schmolke
authors.affiliation: Department of Pathology, Yale School of Medicine, New Haven, Connecticut, USA.
authors.forename: Hailong
authors.initials: H
authors.lastname: Meng
authors.affiliation: Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: James
authors.initials: J
authors.lastname: Wetmur
authors.affiliation: Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA Global Health & Emerging Pathogens Institute at Icahn School of Medicine, New York, New York, USA Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Adolfo
authors.initials: A
authors.lastname: García-Sastre
authors.affiliation: Department of Pathology, Yale School of Medicine, New Haven, Connecticut, USA Interdepartmental Program in Computational Biology and Bioinformatics, Yale University, New Haven, Connecticut, USA steven.kleinstein@yale.edu stuart.sealfon@mssm.edu.
authors.forename: Steven H
authors.initials: SH
authors.lastname: Kleinstein
authors.affiliation: Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, New York, USA Center for Translational Systems Biology, Icahn School of Medicine at Mount Sinai, New York, New York, USA steven.kleinstein@yale.edu stuart.sealfon@mssm.edu.
authors.forename: Stuart C
authors.initials: SC
authors.lastname: Sealfon
mesh_terms: D000940:Antigenic Variation; D003713:Dendritic Cells / Q000276:immunology* / Q000821:virology; D005060:Europe / Q000453:epidemiology; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D049673:History, 20th Century; D049674:History, 21st Century; D054884:Host-Pathogen Interactions; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000235:genetics / Q000276:immunology*; D064149:Influenza Pandemic, 1918-1919 / Q000266:history*; D007251:Influenza, Human / Q000453:epidemiology* / Q000235:genetics / Q000266:history / Q000276:immunology; D007372:Interferons / Q000235:genetics / Q000276:immunology; D017720:Molecular Epidemiology; D016328:NF-kappa B / Q000235:genetics / Q000276:immunology; D058873:Pandemics; D016865:Reassortant Viruses / Q000235:genetics / Q000276:immunology*; D011995:Recombination, Genetic; D012621:Seasons; D015398:Signal Transduction; D013997:Time Factors; D014481:United States / Q000453:epidemiology
chemical_list: D016328:NF-kappa B; D007372:Interferons