In this study, we showed that, compared with prion-uninfected control N2aC24 cells, two different prion-infected cells, N2aC24L1-3 and N2aC24Chm cells, activated the NLRP3 inflammasome after IAV/WSN infection and were highly resistant to IAV/WSN-induced necroptosis, suggesting that PrPSc-prions might play a functional role in activation of the NLRP3 inflammasome and suppression of necroptosis after viral infections. The gene discussed is NLRP3; the disease is infection.