Deficiency of USP22, even in the absence of exogenous IFNs or viral infection, was sufficient to potently upregulate a wide variety of ISGs, including ISG15, 2’-5’-oligoadenylate synthetase 2 (OAS2), as well as IFN-α, -β and -λ (Fig. 5B), identifying USP22 as important negative regulator of IFN signaling and ISG expression in APL cells. This evidence concerns the gene IFNA1 and viral infectious disease.