Severe viral respiratory infections in children with IFIH1 loss-of-function mutations

Asgari, Samira; Schlapbach, Luregn J; Anchisi, Stéphanie; Hammer, Christian; Bartha, Istvan; Junier, Thomas; Mottet-Osman, Geneviève; Posfay Barbe, Clara; Longchamp, David; Stocker, Martin; Cordey, Samuel; Kaiser, Laurent; Riedel, Thomas; Kenna, Tony; Long, Deborah; Schibler, Andreas; Telenti, Amalio; Tapparel, Caroline; McLaren, Paul J; Garcin, Dominique; Fellay, Jacques

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Title		Severe viral respiratory infections in children with IFIH1 loss-of-function mutations
Authors		Asgari, Samira Schlapbach, Luregn J Anchisi, Stéphanie Hammer, Christian Bartha, Istvan Junier, Thomas Mottet-Osman, Geneviève Posfay Barbe, Clara Longchamp, David Stocker, Martin Cordey, Samuel Kaiser, Laurent Riedel, Thomas Kenna, Tony Long, Deborah Schibler, Andreas Telenti, Amalio Tapparel, Caroline McLaren, Paul J Garcin, Dominique Fellay, Jacques show all authors [1 - 21]
Published in		Proceedings of the National Academy of Sciences. 2017, vol. 114, no. 31, p. 8342-8347
Abstract		Viral respiratory infections are usually mild and self-limiting; still they exceptionally result in life-threatening infections in previously healthy children. To investigate a potential genetic cause, we recruited 120 previously healthy children requiring support in intensive care because of a severe illness caused by a respiratory virus. Using exome and transcriptome sequencing, we identified and characterized three rare loss-of-function variants in IFIH1, which encodes an RIG-I-like receptor involved in the sensing of viral RNA. Functional testing of the variants IFIH1 alleles demonstrated that the resulting proteins are unable to induce IFN-β, are intrinsically less stable than wild-type IFIH1, and lack ATPase activity. In vitro assays showed that IFIH1 effectively restricts replication of human respiratory syncytial virus and rhinoviruses. We conclude that IFIH1 deficiency causes a primary immunodeficiency manifested in extreme susceptibility to common respiratory RNA viruses.
Identifiers		DOI: 10.1073/pnas.1704259114 PMID: 28716935
Full text		Article (Author postprint) (3.8 MB) - Free access
Structures		Faculté de médecine / Section de médecine clinique / Département de médecine interne des spécialités Faculté de médecine / Section de médecine fondamentale / Département de microbiologie et médecine moléculaire
Research groups		Virologie moléculaire (275) Groupe Laurent Kaiser (virologie clinique) (668)
Project		FNS: 31003A_163129
Citation (ISO format)		ASGARI, Samira et al. Severe viral respiratory infections in children with IFIH1 loss-of-function mutations. In: Proceedings of the National Academy of Sciences, 2017, vol. 114, n° 31, p. 8342-8347. https://archive-ouverte.unige.ch/unige:96901