We then showed that, in prion-infected cells, the nuclear translocation of the transcription factor NF-κB was disturbed after IAV/WSN infection, therefore suppressing the gene expression of mitochondrial superoxide dismutase (SOD2), elevating mitochondrial reactive oxygen species (mtROS), and eventually activating the NLRP3 inflammasome. This evidence concerns the gene NFKB1 and early-onset parkinsonism-intellectual disability syndrome.