IFIH1 and viral infectious disease: Furthermore, either mutation in MDA5 decreased the induction of IFNA gene expression in both the absence and presence of TRIM4 overexpression and consequently attenuated the inhibitory effects on viral infection and replication, and double-point mutation declined more (Fig 6C); in addition, nsp8 inhibited IFNA gene expression and increased viral gene expression regardless of whether wild-type or mutated MDA5 was overexpressed (Fig 6D).