title: Club cells surviving influenza A virus infection induce temporary nonspecific antiviral immunity.
abstract: A brief window of antigen-nonspecific protection has been observed after influenza A virus (IAV) infection. Although this temporary immunity has been assumed to be the result of residual nonspecific inflammation, this period of induced immunity has not been fully studied. Because IAV has long been characterized as a cytopathic virus (based on its ability to rapidly lyse most cell types in culture), it has been a forgone conclusion that directly infected cells could not be contributing to this effect. Using a Cre recombinase-expressing IAV, we have previously shown that club cells can survive direct viral infection. We show here not only that these cells can eliminate all traces of the virus and survive but also that they acquire a heightened antiviral response phenotype after surviving. Moreover, we experimentally demonstrate temporary nonspecific viral immunity after IAV infection and show that surviving cells are required for this phenotype. This work characterizes a virally induced modulation of the innate immune response that may represent a new mechanism to prevent viral diseases.
authors.affiliation: Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029;
authors.forename: Jennifer R
authors.initials: JR
authors.lastname: Hamilton
authors.affiliation: Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029;
authors.forename: David
authors.initials: D
authors.lastname: Sachs
authors.affiliation: Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029;
authors.forename: Jean K
authors.initials: JK
authors.lastname: Lim
authors.affiliation: Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029; Department of Microbiology and Immunology, University of Minnesota Medical School, Minneapolis, MN 55455;
authors.forename: Ryan A
authors.initials: RA
authors.lastname: Langlois
authors.affiliation: Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029; Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029;
authors.forename: Peter
authors.initials: P
authors.lastname: Palese
authors.affiliation: Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029; Department of Molecular Genetics and Microbiology, Duke University, Durham, NC 27710 nicholas.heaton@duke.edu.
authors.forename: Nicholas S
authors.initials: NS
authors.lastname: Heaton
mesh_terms: D000818:Animals; D002460:Cell Line; D056738:Cross Protection / Q000276:immunology*; D016207:Cytokines / Q000276:immunology; D004285:Dogs; D057809:HEK293 Cells; D054884:Host-Pathogen Interactions; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology*; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D007251:Influenza, Human / Q000276:immunology* / Q000821:virology; D008168:Lung / Q000276:immunology; D061985:Madin Darby Canine Kidney Cells; D051379:Mice; D008810:Mice, Inbred C57BL; D009976:Orthomyxoviridae Infections / Q000276:immunology* / Q000821:virology
chemical_list: D016207:Cytokines
keywords: RNA sequencing; alternative cell fate; antiviral immunity; influenza virus