PPM1B negatively regulates antiviral response via dephosphorylating TBK1

► PPM1B inhibits TBK1-mediated antiviral response. ► PPM1B dephosphorylates TBK1 in vivo and in vitro. ► PPM1B inhibits antiviral response and facilitates VSV replication in the cells. ► Suppression of PPM1B enhances virus-induced IRF3 phosphorylation and IFNβ production.