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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 (Accepted version) (3.8 MB) - public document Free access
Structures
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
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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. doi: 10.1073/pnas.1704259114 https://archive-ouverte.unige.ch/unige:96901

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Deposited on : 2017-09-20

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