Although both VSV and EMCV caused neuroinvasive disease, induced IFN-β, Ifit1 and Ifit2 in the brain and type I IFN action was required for protection against both viruses, Ifit2 was critical only for protection against VSV; the absence of either Ifit1 or Ifit2 did not exacerbate susceptibility to EMCV. This evidence concerns the gene IFNB1 and glycogen storage disease VI.