HSE is generally sporadic rather than familial, but mutations of TLR3, UNC93B1, TRIF, TRAF3, TBK1, and IRF3 have been identified as causal of HSE, and the likelihood of developing HSE is thought to be about 100 times higher than that in the general population for carriers of severely hypomorphic or null TLR3 alleles (1). Here, IRF3 is linked to herpes simplex encephalitis.