Inhibits the establishment of the antiviral state in the infected cell. Prevents the phosphorylation of the host eukaryotic translation initiation factor eIF-2alpha and thus the shutoff of viral and cellular protein synthesis by directly interacting with EIF2AK2/PKR. May also participate in viral DNA replication by interacting with the DNA polymerase accessory protein and the lytic origin of replication, oriLyt. Interacts (via N-terminus) with the viral DNA polymerase accessory subunit UL44. Interacts (via C-terminus) with host EIF2AK2/PKR. Isoform IRS1-263 is predominantly nuclear. Belongs to the herpesviridae US22 family.