Indeed, RIG-I knockdown and transfection with siRNA directed to RIG-I attenuates TNF-α responses in microglia and astrocytes.70 A recent study described a child afflicted by HSE who was found to harbour a compound heterozygous variant in the GTF3A gene, which encodes for the transcription factor IIIA (TFIIIA); a moonlighting protein with protective properties against HSV through production of the RIG-I ligand, RNA5SP141.71 This patient (and his sister) exhibited a diminished IFN-I response to HSV-1 in isolated patient fibroblasts and GTF3A gene-edited cells. Here, RIGI is linked to herpes simplex encephalitis.