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

• Published in: Science (American Association for the Advancement of Science) Vol. 348; no. 6233; pp. 448 - 453
• Main Authors: Ciancanelli, Michael J, Huang, Sarah X L, Luthra, Priya, Garner, Hannah, Itan, Yuval, Volpi, Stefano, Lafaille, Fabien G, Trouillet, Céline, Schmolke, Mirco, Albrecht, Randy A, Israelsson, Elisabeth, Lim, Hye Kyung, Casadio, Melina, Hermesh, Tamar, Lorenzo, Lazaro, Leung, Lawrence W, Pedergnana, Vincent, Boisson, Bertrand, Okada, Satoshi, Picard, Capucine, Ringuier, Benedicte, Troussier, Françoise, Chaussabel, Damien, Abel, Laurent, Pellier, Isabelle, Notarangelo, Luigi D, García-Sastre, Adolfo, Basler, Christopher F, Geissmann, Frédéric, Zhang, Shen-Ying, Snoeck, Hans-Willem, Casanova, Jean-Laurent
• Format: Journal Article
• Language: English
• Published: United States American Association for the Advancement of Science (AAAS) 24.04.2015
• Subjects: Cancer; Child; Dendritic Cells - immunology; Female; Fibroblasts - immunology; Genes, Recessive; Heterozygote; Humans; Induced Pluripotent Stem Cells - immunology; Influenza A Virus, H1N1 Subtype; Influenza, Human - complications; Influenza, Human - genetics; Influenza, Human - immunology; Interferon Regulatory Factor-7 - genetics; Interferon Type I - biosynthesis; Interferon Type I - genetics; Leukocytes - immunology; Life Sciences; Lung - immunology; Mutation; Respiratory Distress Syndrome - genetics; Respiratory Distress Syndrome - immunology; Respiratory Distress Syndrome - virology; Respiratory Mucosa - immunology
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.aaa1578

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.