We showed here that prion-infected cells were higher in resistance to IAV/WSN infection than control prion-uninfected cells, by increasing cytosolic PrP and subsequently activating the NLRP3 inflammasome and suppressing necroptosis, suggesting the protective role for PrPSc prions against IAV/WSN infection. This evidence concerns the gene NLRP3 and early-onset parkinsonism-intellectual disability syndrome.