Scientific article
Open access

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

Published inProceedings of the National Academy of Sciences, vol. 114, no. 31, p. 8342-8347
Publication date2017

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.

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
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Article (Accepted version)
ISSN of the journal0027-8424

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