The Ifih1ΔHel1 mutation delayed both uninfected/spontaneous and CVB3-accelerated T1D, which was partly due to reductions in MDA5-mediated ATP hydrolysis, IFN-α/β synthesis, TNF+ macrophages, IFN-γ+CD4+ T cells, and perforin+CD8+ T cells in the pancreata. Here, PRF1 is linked to type 1 diabetes mellitus.