Upon SeV or EMCV infection, macrophages or MEFs with the deficiency of USP18 showed impaired phosphorylation of TBK1 and IRF3, expression of Ifnb and Ccl5, and production of IFN-β, indicating that USP18 plays a positive role in regulating viral-induced type-I interferon response. Here, TBK1 is linked to infection.