Herpes simplex encephalitis in a patient with a distinctive form of inherited IFNAR1 deficiency

Inborn errors of TLR3-dependent IFN-α/β– and IFN-λ–mediated immunity in the CNS can underlie herpes simplex virus 1 (HSV-1) encephalitis (HSE). The respective contributions IFN-α/β IFN-λ are unknown. We report a child homozygous for genomic deletion entire coding sequence part 3′-UTR last exon IFNAR1, who died HSE at age 2 years. An older cousin following vaccination against measles, mumps, rubella 12 months age, another 17-year-old same variant has had other, less severe, viral illnesses. encoded IFNAR1 protein is expressed on cell surface but truncated cannot interact with tyrosine kinase TYK2. patient’s fibroblasts EBV-B cells did not respond to IFN-α2b or IFN-β, terms STAT1, STAT2, STAT3 phosphorylation genome-wide induction IFN-stimulated genes. were susceptible viruses, including HSV-1, even presence exogenous IFN-β. therefore consequence inherited complete deficiency. This disease occurred natural conditions, unlike those previously reported other patients IFNAR2 experiment nature indicates that essential anti–HSV-1 CNS.