Severe viral respiratory infections in children with IFIH1 loss-of-function mutations.
Proc Natl Acad Sci U S A
; 114(31): 8342-8347, 2017 08 01.
Article
en En
| MEDLINE
| ID: mdl-28716935
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-ß, 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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Virus Sincitiales Respiratorios
/
Infecciones del Sistema Respiratorio
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Rhinovirus
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Interferón beta
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Predisposición Genética a la Enfermedad
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Helicasa Inducida por Interferón IFIH1
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Síndromes de Inmunodeficiencia
Tipo de estudio:
Observational_studies
/
Risk_factors_studies
Límite:
Child, preschool
/
Female
/
Humans
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Infant
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Male
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Newborn
Idioma:
En
Revista:
Proc Natl Acad Sci U S A
Año:
2017
Tipo del documento:
Article
País de afiliación:
Suiza