Several fatal cases of Herpes simplex encephalitis (HSE) in newborns were associated with defects in genes encoding signal transduction factors of the IFN pathway, such as Toll/interleukin-1 receptor domain-containing adaptor-inducing interferon-β (TRIF), TANK-binding kinase 1 (TBK-1), Toll-like receptor 3 (TLR3) or tumor necrosis factor receptor-associated factor 3 (TRAF3). The gene discussed is TLR3; the disease is herpes simplex encephalitis.