Thus, together with the previous report on HSV-1 infection in the CNS after intranasal infection of TRIF-deficient mice27, and the extensive literature on defects in the TLR3 pathways in HSE patients6, 7, 8, 9, 10, the present study corroborates the cGAS–STING and the TLR3–TRIF pathways as the main innate sensing pathways conferring control of HSV-1 infection in the CNS. Here, TLR3 is linked to herpes simplex encephalitis.