In this study, by generating nsp15-defective recombinant IBV, we found that compared to the wild type virus, infection with rIBV-nsp15-H238A lead to dsRNA accumulation, PKR activation, robust formation of SG as well as up-regulation of IFN-β, which ultimately coincided with impaired rIBV-nsp15-H238A replication. This evidence concerns the gene EIF2AK2 and infection.