TY - JOUR
T1 - Life-threatening influenza and impaired interferon amplification in human IRF7 deficiency
AU - Ciancanelli, Michael J.
AU - Huang, Sarah X.L.
AU - Luthra, Priya
AU - Garner, Hannah
AU - Itan, Yuval
AU - Volpi, Stefano
AU - Lafaille, Fabien G.
AU - Trouillet, Céline
AU - Schmolke, Mirco
AU - Albrecht, Randy A.
AU - Israelsson, Elisabeth
AU - Lim, Hye Kyung
AU - Casadio, Melina
AU - Hermesh, Tamar
AU - Lorenzo, Lazaro
AU - Leung, Lawrence W.
AU - Pedergnana, Vincent
AU - Boisson, Bertrand
AU - Okada, Satoshi
AU - Picard, Capucine
AU - Ringuier, Benedicte
AU - Troussier, Françoise
AU - Chaussabel, Damien
AU - Abel, Laurent
AU - Pellier, Isabelle
AU - Notarangelo, Luigi D.
AU - García-Sastre, Adolfo
AU - Basler, Christopher F.
AU - Geissmann, Frédéric
AU - Zhang, Shen Ying
AU - Snoeck, Hans Willem
AU - Casanova, Jean Laurent
N1 - Publisher Copyright:
© 2015, American Association for the Advancement of Science. All rights reserved.
PY - 2015/4/24
Y1 - 2015/4/24
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84928377935&partnerID=8YFLogxK
U2 - 10.1126/science.aaa1578
DO - 10.1126/science.aaa1578
M3 - Article
C2 - 25814066
AN - SCOPUS:84928377935
SN - 0036-8075
VL - 348
SP - 448
EP - 453
JO - Science
JF - Science
IS - 6233
ER -