title: Infectious disease. Life-threatening influenza and impaired interferon amplification in human IRF7 deficiency.
abstract: Severe influenza disease strikes otherwise healthy children and remains unexplained. We report compound heterozygous null mutations in IRF7, which encodes the transcription factor interferon regulatory factor 7, in an otherwise healthy child who suffered life-threatening influenza during primary infection. In response to influenza virus, the patient's leukocytes and plasmacytoid dendritic cells produced very little type I and III interferons (IFNs). Moreover, the patient's dermal fibroblasts and induced pluripotent stem cell (iPSC)-derived pulmonary epithelial cells produced reduced amounts of type I IFN and displayed increased influenza virus replication. These findings suggest that IRF7-dependent amplification of type I and III IFNs is required for protection against primary infection by influenza virus in humans. They also show that severe influenza may result from single-gene inborn errors of immunity.
authors: St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA.
authors: Michael J
authors: MJ
authors: Ciancanelli
authors: Columbia Center for Translational Immunology, Columbia University Medical Center, New York, NY, USA. Department of Medicine, Columbia University Medical Center, New York, NY, USA.
authors: Sarah X L
authors: SX
authors: Huang
authors: Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors: Priya
authors: P
authors: Luthra
authors: Centre for Molecular and Cellular Biology of Inflammation (CMCBI), King's College London, London SE1 1UL, UK.
authors: Hannah
authors: H
authors: Garner
authors: St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA.
authors: Yuval
authors: Y
authors: Itan
authors: Division of Immunology and Manton Center for Orphan Disease Research, Children's Hospital, Harvard Medical School, Boston, MA, USA. Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, 16132 Genoa, Italy.
authors: Stefano
authors: S
authors: Volpi
authors: St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA.
authors: Fabien G
authors: FG
authors: Lafaille
authors: Centre for Molecular and Cellular Biology of Inflammation (CMCBI), King's College London, London SE1 1UL, UK.
authors: Céline
authors: C
authors: Trouillet
authors: Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors: Mirco
authors: M
authors: Schmolke
authors: Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors: Randy A
authors: RA
authors: Albrecht
authors: Department of Systems Immunology, Benaroya Research Institute at Virginia Mason, Seattle, WA, USA.
authors: Elisabeth
authors: E
authors: Israelsson
authors: St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA.
authors: Hye Kyung
authors: HK
authors: Lim
authors: St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA.
authors: Melina
authors: M
authors: Casadio
authors: St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA.
authors: Tamar
authors: T
authors: Hermesh
authors: Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM UMR1163, Paris, France. University Paris Descartes, Imagine Institute, Paris, France.
authors: Lazaro
authors: L
authors: Lorenzo
authors: Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors: Lawrence W
authors: LW
authors: Leung
authors: Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM UMR1163, Paris, France. University Paris Descartes, Imagine Institute, Paris, France.
authors: Vincent
authors: V
authors: Pedergnana
authors: St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA.
authors: Bertrand
authors: B
authors: Boisson
authors: St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA. Department of Pediatrics, Hiroshima University Graduate School of Biomedical & Health Sciences, Hiroshima, Japan.
authors: Satoshi
authors: S
authors: Okada
authors: St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA. Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM UMR1163, Paris, France. University Paris Descartes, Imagine Institute, Paris, France. Study Centre for Primary Immunodeficiencies, AP-HP, Necker Hospital, Paris, France.
authors: Capucine
authors: C
authors: Picard
authors: Pediatric Intensive Care Unit, University Hospital, Angers, France.
authors: Benedicte
authors: B
authors: Ringuier
authors: General Pediatrics Unit, University Hospital, Angers, France.
authors: Françoise
authors: F
authors: Troussier
authors: Department of Systems Immunology, Benaroya Research Institute at Virginia Mason, Seattle, WA, USA. Department of Systems Biology, Sidra Medical and Research Center, Doha, Qatar.
authors: Damien
authors: D
authors: Chaussabel
authors: St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA. Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM UMR1163, Paris, France. University Paris Descartes, Imagine Institute, Paris, France.
authors: Laurent
authors: L
authors: Abel
authors: Pediatric Immunology, Hematology and Oncology Unit, University Hospital Centre of Angers, Angers, France. INSERM U892, CNRS U6299, Angers, France.
authors: Isabelle
authors: I
authors: Pellier
authors: Division of Immunology and Manton Center for Orphan Disease Research, Children's Hospital, Harvard Medical School, Boston, MA, USA.
authors: Luigi D
authors: LD
authors: Notarangelo
authors: Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Department of Medicine, Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors: Adolfo
authors: A
authors: García-Sastre
authors: Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors: Christopher F
authors: CF
authors: Basler
authors: Centre for Molecular and Cellular Biology of Inflammation (CMCBI), King's College London, London SE1 1UL, UK.
authors: Frédéric
authors: F
authors: Geissmann
authors: St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA. Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM UMR1163, Paris, France. University Paris Descartes, Imagine Institute, Paris, France.
authors: Shen-Ying
authors: SY
authors: Zhang
authors: Columbia Center for Translational Immunology, Columbia University Medical Center, New York, NY, USA. Department of Medicine, Columbia University Medical Center, New York, NY, USA.
authors: Hans-Willem
authors: HW
authors: Snoeck
authors: St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA. Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM UMR1163, Paris, France. University Paris Descartes, Imagine Institute, Paris, France. Pediatric Immuno-Hematology Unit, Necker Hospital for Sick Children, AP-HP, Paris, France. Howard Hughes Medical Institute, New York, NY, USA. jean-laurent.casanova@rockefeller.edu.
authors: Jean-Laurent
authors: JL
authors: Casanova
mesh_terms: D002648:Child; D003713:Dendritic Cells / Q000276:immunology; D005260:Female; D005347:Fibroblasts / Q000276:immunology; D005808:Genes, Recessive; D006579:Heterozygote; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000276:immunology; D053118:Influenza A Virus, H1N1 Subtype; D007251:Influenza, Human / Q000150:complications / Q000235:genetics / Q000276:immunology*; D050839:Interferon Regulatory Factor-7 / Q000235:genetics*; D007370:Interferon Type I / Q000096:biosynthesis* / Q000235:genetics; D007962:Leukocytes / Q000276:immunology; D008168:Lung / Q000276:immunology; D009154:Mutation; D012128:Respiratory Distress Syndrome / Q000235:genetics / Q000276:immunology* / Q000821:virology; D020545:Respiratory Mucosa / Q000276:immunology
chemical_list: C494234:IRF7 protein, human; D050839:Interferon Regulatory Factor-7; D007370:Interferon Type I