Upon viral infection,host deploy a diversity of innate receptors including TLRs,RLRs and cytosolic DNA sensors to trigger type Ⅰ interferon response.The induction of type Ⅰ interferons IFNα/β,which depends on the transcriptional factors IRF3 and NFκB,is under stringent control by multi-layered mechanisms.While TBK1-mediated phosphorylation has been demonstrated to be essential for the activation of IRF3,we recently found that protein phosphatases PP2A and MKP5 are also involved in the regulation of IRF3 activation.By in vitro and in vivo assays,we showed that PP2A and MKP5 are bona fide phosphatases for IRF3 and negatively regulators of viruses-induced IFN response.