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Title

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

Authors
Asgari, Samira
Schlapbach, Luregn J
Hammer, Christian
Bartha, Istvan
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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
PMID: 28716935
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Article (Author postprint) (3.8 MB) - public document Free access
Structures
Research groups Virologie moléculaire (275)
Groupe Laurent Kaiser (virologie clinique) (668)
Project FNS: 31003A_163129
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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

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Deposited on : 2017-09-20

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