Fig. 5

DDX5 modulates virus infection and replication: A DDX5 suppresses IFN-I antiviral IIRs by interacting with PP2A-Cβ to deactivate IRF3 to inhibit IFN-I production. B DDX5 inhibits antiviral innate immunity by promoting m6A-methylated antiviral transcripts. (i) DDX5 interacts with METTL3 to regulate methylation of mRNA through affecting the METTL3-METTL14 heterodimer complex; (ii) DDX5 promotes m6A modification and nuclear export of DHX58, p65, and IKKγ transcripts by binding the conserved UGCUGCAG element; (iii) stable IKKγ and p65 transcripts underwent YTHDF2-dependent mRNA decay, whereas DHX58 translation was promoted, resulting in the inhibited antiviral IIRs by DDX5 blocking the p65 pathway and activating the DHX58-TBK1 pathway. As a result, DDX5 suppresses antiviral innate immunity. C DDX5 suppressed IFN-β production and inhibited the expression of IRF1 and thus, promoted MDV replication. D DDX1, DDX5 and DDX6 promoted SARS-CoV-2 infection and replication by suppressing host IIRs, while DDX21 and MOV10 suppressed SARS-CoV-2 infection and replication. E DDX5 suppresses antiviral innate immunity and promotes replication of IAV