About 5% of children with HSE have experimentally proven autosomal recessive or autosomal dominant deficiency of the TLR3–IFNα/β circuit, which governs cell-intrinsic immunity in cortical neurons8–17,24,25, and another roughly 2% have autosomal dominant or autosomal recessive deficiencies that govern other antiviral mechanisms in the forebrain (snoRNA31, RIPK3 and TFIIIA) or brainstem (DBR1)18,21–23. Here, IFNA1 is linked to herpes simplex encephalitis.