The proposed working model. IBV infection activates MEK1/2-ERK1/2 signaling, which protects cells from death by reducing the level of Mcl-1 and Bcl-2, thereby supporting efficient IBV replication. The activation of ERK1/2 pathway induces the phosphatase DUSP6 expression. DUSP6 forms a negative regulation loop by dephosphorylating ERK1/2, to restrict this prosurvival signal. The upregulation of DUSP6 promotes cell death and impairs IBV replication, representing one of the host antiviral responses. U0126 inhibits the activation of ERK1/2 and promotes cell death, thereby suppressing IBV replication, while BCI inhibits DUSP6 and promotes ERK1/2 signaling/cell survival, thereby promoting IBV replication.