title: Long-term survival of influenza virus infected club cells drives immunopathology.
abstract: Respiratory infection of influenza A virus (IAV) is frequently characterized by extensive immunopathology and proinflammatory signaling that can persist after virus clearance. In this report, we identify cells that become infected, but survive, acute influenza virus infection. We demonstrate that these cells, known as club cells, elicit a robust transcriptional response to virus infection, show increased interferon stimulation, and induce high levels of proinflammatory cytokines after successful viral clearance. Specific depletion of these surviving cells leads to a reduction in lung tissue damage associated with IAV infection. We propose a model in which infected, surviving club cells establish a proinflammatory environment aimed at controlling virus levels, but at the same time contribute to lung pathology.
authors.affiliation: Department of Microbiology, Global Health and Emerging Pathogens Institute, and Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029.
authors.forename: Nicholas S
authors.initials: NS
authors.lastname: Heaton
authors.affiliation: Department of Microbiology, Global Health and Emerging Pathogens Institute, and Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029 Department of Microbiology, Global Health and Emerging Pathogens Institute, and Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029.
authors.forename: Ryan A
authors.initials: RA
authors.lastname: Langlois
authors.affiliation: Department of Microbiology, Global Health and Emerging Pathogens Institute, and 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, Global Health and Emerging Pathogens Institute, and Department of Genetics and Genomic Sciences, 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, Global Health and Emerging Pathogens Institute, and Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029 peter.palese@mssm.edu benjamin.tenOever@mssm.edu.
authors.forename: Peter
authors.initials: P
authors.lastname: Palese
authors.affiliation: Department of Microbiology, Global Health and Emerging Pathogens Institute, and Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029 Department of Microbiology, Global Health and Emerging Pathogens Institute, and Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029 peter.palese@mssm.edu benjamin.tenOever@mssm.edu.
authors.forename: Benjamin R
authors.initials: BR
authors.lastname: tenOever
mesh_terms: D000818:Animals; D019070:Cell Lineage; D002470:Cell Survival; D004195:Disease Models, Animal; D005347:Fibroblasts / Q000276:immunology / Q000473:pathology / Q000821:virology; D053118:Influenza A Virus, H1N1 Subtype / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology*; D019426:Integrases / Q000235:genetics; D008168:Lung / Q000276:immunology / Q000473:pathology / Q000821:virology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009976:Orthomyxoviridae Infections / Q000235:genetics / Q000276:immunology / Q000821:virology; D012333:RNA, Messenger / Q000235:genetics; D012367:RNA, Viral / Q000235:genetics; D011995:Recombination, Genetic
chemical_list: D012333:RNA, Messenger; D012367:RNA, Viral; C045073:Cre recombinase; D019426:Integrases