Fig 4B shows that DYRK2-WT but not DYRK2-MT caused the ubiquitination and downregulation of TBK1. As the interactions between DYRK2 and TBK1 were viral infection-dependent under physiological conditions (Fig 3D), we also wanted to determine whether viral infection caused the ubiquitination of endogenous TBK1. Endogenous TBK1 was ubiquitinated and downregulated after virus infection (Fig 4C). Conversely, DYRK2 knockdown markedly diminished the virus-induced ubiquitination and downregulation of TBK1 (Fig 4C). Here, TBK1 is linked to viral infectious disease.