Monogenic immunodeficiencies rendering the host susceptible to HSE predominantly involves inborn errors of TLR3-dependent IFN-α/β- and IFN-λ-mediated immunity.54,127,128 An isolated forebrain form of HSE is found in some children with errors in TLR3 pathway genes23,47,54,55 or in SNORA31. Here, TLR3 is linked to immunodeficiency disease.