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, Klara; 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

doi:10.1073/pnas.1704259114

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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, Klara 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 (Accepted version) (3.8 MB) - Free access
Structures		Faculté de médecine / Section de médecine clinique / Département de médecine Faculté de médecine / Section de médecine fondamentale / Département de microbiologie et médecine moléculaire
Research groups		Virologie moléculaire (275) Groupe Laurent Kaiser (virologie clinique) (668) Identification des facteurs clés impliqués dans la pathogénèse des rhinovirus et entérovirus (953) Recherche en infectiologie pédiatrique et en pédiatrie générale (853)
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. doi: 10.1073/pnas.1704259114 https://archive-ouverte.unige.ch/unige:96901