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Life-threatening influenza pneumonitis in a child with inherited IRF9 deficiency.
Hernandez, Nicholas; Melki, Isabelle; Jing, Huie; Habib, Tanwir; Huang, Susie S Y; Danielson, Jeffrey; Kula, Tomasz; Drutman, Scott; Belkaya, Serkan; Rattina, Vimel; Lorenzo-Diaz, Lazaro; Boulai, Anais; Rose, Yoann; Kitabayashi, Naoki; Rodero, Mathieu P; Dumaine, Cecile; Blanche, Stéphane; Lebras, Marie-Noëlle; Leung, Man Chun; Mathew, Lisa Sara; Boisson, Bertrand; Zhang, Shen-Ying; Boisson-Dupuis, Stephanie; Giliani, Silvia; Chaussabel, Damien; Notarangelo, Luigi D; Elledge, Stephen J; Ciancanelli, Michael J; Abel, Laurent; Zhang, Qian; Marr, Nico; Crow, Yanick J; Su, Helen C; Casanova, Jean-Laurent.
Afiliação
  • Hernandez N; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY.
  • Melki I; Pediatric Immunology-Hematology and Rheumatology Unit, Assistance Publique-Hôpitaux de Paris, Necker Hospital for Sick Children, Paris, France.
  • Jing H; General Pediatrics, Infectious Disease and Internal Medicine Department, Assistance Publique-Hôpitaux de Paris, Robert Debré Hospital, Paris, France.
  • Habib T; Laboratory of Neurogenetics and Neuroinflammation, Institut National de la Santé et de la Recherche Médicale UMR 1163, Paris, France.
  • Huang SSY; Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD.
  • Danielson J; Division of Translational Medicine, Sidra Medicine, Doha, Qatar.
  • Kula T; Division of Translational Medicine, Sidra Medicine, Doha, Qatar.
  • Drutman S; Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD.
  • Belkaya S; Division of Genetics, Department of Genetics, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
  • Rattina V; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY.
  • Lorenzo-Diaz L; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY.
  • Boulai A; Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de la Santé et de la Recherche Médicale U1163, Paris, France.
  • Rose Y; Paris Descartes University, Imagine Institute, Paris, France.
  • Kitabayashi N; Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de la Santé et de la Recherche Médicale U1163, Paris, France.
  • Rodero MP; Paris Descartes University, Imagine Institute, Paris, France.
  • Dumaine C; Laboratory of Neurogenetics and Neuroinflammation, Institut National de la Santé et de la Recherche Médicale UMR 1163, Paris, France.
  • Blanche S; Laboratory of Neurogenetics and Neuroinflammation, Institut National de la Santé et de la Recherche Médicale UMR 1163, Paris, France.
  • Lebras MN; Laboratory of Neurogenetics and Neuroinflammation, Institut National de la Santé et de la Recherche Médicale UMR 1163, Paris, France.
  • Leung MC; Laboratory of Neurogenetics and Neuroinflammation, Institut National de la Santé et de la Recherche Médicale UMR 1163, Paris, France.
  • Mathew LS; Pediatric Immunology-Hematology and Rheumatology Unit, Assistance Publique-Hôpitaux de Paris, Necker Hospital for Sick Children, Paris, France.
  • Boisson B; General Pediatrics, Infectious Disease and Internal Medicine Department, Assistance Publique-Hôpitaux de Paris, Robert Debré Hospital, Paris, France.
  • Zhang SY; Pediatric Immunology-Hematology and Rheumatology Unit, Assistance Publique-Hôpitaux de Paris, Necker Hospital for Sick Children, Paris, France.
  • Boisson-Dupuis S; Pediatric Pulmonology, Infectious Disease and Internal Medicine Department, Assistance Publique-Hôpitaux de Paris, Robert Debré Hospital, Paris, France.
  • Giliani S; Division of Translational Medicine, Sidra Medicine, Doha, Qatar.
  • Chaussabel D; Division of Translational Medicine, Sidra Medicine, Doha, Qatar.
  • Notarangelo LD; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY.
  • Elledge SJ; Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de la Santé et de la Recherche Médicale U1163, Paris, France.
  • Ciancanelli MJ; Paris Descartes University, Imagine Institute, Paris, France.
  • Abel L; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY.
  • Zhang Q; Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de la Santé et de la Recherche Médicale U1163, Paris, France.
  • Marr N; Paris Descartes University, Imagine Institute, Paris, France.
  • Crow YJ; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY.
  • Su HC; Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de la Santé et de la Recherche Médicale U1163, Paris, France.
  • Casanova JL; Paris Descartes University, Imagine Institute, Paris, France.
J Exp Med ; 215(10): 2567-2585, 2018 10 01.
Article em En | MEDLINE | ID: mdl-30143481
ABSTRACT
Life-threatening pulmonary influenza can be caused by inborn errors of type I and III IFN immunity. We report a 5-yr-old child with severe pulmonary influenza at 2 yr. She is homozygous for a loss-of-function IRF9 allele. Her cells activate gamma-activated factor (GAF) STAT1 homodimers but not IFN-stimulated gene factor 3 (ISGF3) trimers (STAT1/STAT2/IRF9) in response to IFN-α2b. The transcriptome induced by IFN-α2b in the patient's cells is much narrower than that of control cells; however, induction of a subset of IFN-stimulated gene transcripts remains detectable. In vitro, the patient's cells do not control three respiratory viruses, influenza A virus (IAV), parainfluenza virus (PIV), and respiratory syncytial virus (RSV). These phenotypes are rescued by wild-type IRF9, whereas silencing IRF9 expression in control cells increases viral replication. However, the child has controlled various common viruses in vivo, including respiratory viruses other than IAV. Our findings show that human IRF9- and ISGF3-dependent type I and III IFN responsive pathways are essential for controlling IAV.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Orthomyxoviridae / Pneumonia Viral / Alelos / Fator Gênico 3 Estimulado por Interferon, Subunidade gama / Influenza Humana / Homozigoto Limite: Female / Humans / Infant Idioma: En Revista: J Exp Med Ano de publicação: 2018 Tipo de documento: Article
Texto completo
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Orthomyxoviridae / Pneumonia Viral / Alelos / Fator Gênico 3 Estimulado por Interferon, Subunidade gama / Influenza Humana / Homozigoto Limite: Female / Humans / Infant Idioma: En Revista: J Exp Med Ano de publicação: 2018 Tipo de documento: Article