2. Academic Validation
  3. Infectious disease. Life-threatening influenza and impaired interferon amplification in human IRF7 deficiency

Infectious disease. Life-threatening influenza and impaired interferon amplification in human IRF7 deficiency

  • Science. 2015 Apr 24;348(6233):448-53. doi: 10.1126/science.aaa1578.
Michael J Ciancanelli 1,  Sarah X L Huang 2,  Priya Luthra 3,  Hannah Garner 4,  Yuval Itan 1,  Stefano Volpi 5,  Fabien G Lafaille 1,  Céline Trouillet 4,  Mirco Schmolke 3,  Randy A Albrecht 6,  Elisabeth Israelsson 7,  Hye Kyung Lim 1,  Melina Casadio 1,  Tamar Hermesh 1,  Lazaro Lorenzo 8,  Lawrence W Leung 3,  Vincent Pedergnana 8,  Bertrand Boisson 1,  Satoshi Okada 9,  Capucine Picard 10,  Benedicte Ringuier 11,  Françoise Troussier 12,  Damien Chaussabel 13,  Laurent Abel 14,  Isabelle Pellier 15,  Luigi D Notarangelo 16,  Adolfo García-Sastre 17,  Christopher F Basler 3,  Frédéric Geissmann 4,  Shen-Ying Zhang 14,  Hans-Willem Snoeck 2,  Jean-Laurent Casanova 18
Affiliations

Affiliations

  • 1 St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA.
  • 2 Columbia Center for Translational Immunology, Columbia University Medical Center, New York, NY, USA. Department of Medicine, Columbia University Medical Center, New York, NY, USA.
  • 3 Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • 4 Centre for Molecular and Cellular Biology of Inflammation (CMCBI), King's College London, London SE1 1UL, UK.
  • 5 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.
  • 6 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.
  • 7 Department of Systems Immunology, Benaroya Research Institute at Virginia Mason, Seattle, WA, USA.
  • 8 Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM UMR1163, Paris, France. University Paris Descartes, Imagine Institute, Paris, France.
  • 9 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.
  • 10 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.
  • 11 Pediatric Intensive Care Unit, University Hospital, Angers, France.
  • 12 General Pediatrics Unit, University Hospital, Angers, France.
  • 13 Department of Systems Immunology, Benaroya Research Institute at Virginia Mason, Seattle, WA, USA. Department of Systems Biology, Sidra Medical and Research Center, Doha, Qatar.
  • 14 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.
  • 15 Pediatric Immunology, Hematology and Oncology Unit, University Hospital Centre of Angers, Angers, France. INSERM U892, CNRS U6299, Angers, France.
  • 16 Division of Immunology and Manton Center for Orphan Disease Research, Children's Hospital, Harvard Medical School, Boston, MA, USA.
  • 17 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.
  • 18 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. [email protected].
PMID: 25814066 DOI: 10.1126/science.aaa1578
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.

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