DDX20 positively regulates the interferon pathway to inhibit viral infection

The DEAD-box (DDX) family comprises RNA helicases characterized by the conserved sequence D(Asp)-E(Glu)-A(Ala)-D(Asp), participating in various RNA metabolism processes. Some DDX family members have been identified for their crucial roles in viral infections. In this study, RNAi library screening of the DDX family unveiled the antiviral activity of DDX20. Knockdown of DDX20 enhanced the replication of viruses such as vesicular stomatitis virus (VSV) and herpes simplex virus type I (HSV-1), while overexpression of DDX20 significantly diminished the replication level of these viruses. Mechanistically, DDX20 elevated the phosphorylation level of IRF3 induced by external stimuli by facilitating the interaction between TBK1 and IRF3, thereby promoting the expression of IFN-β. The increased IFN-β production, in turn, upregulated the expression of interferon-stimulated genes (ISGs), including Cig5 and IFIT1, thereby exerting the antiviral effect. Finally, in an in vivo infection study, Ddx20 gene-deficient mice exhibited increased susceptibility to viral infection. This study provides new evidence that DDX20 positively modulates the interferon pathway and restricts viral infection.