Inhibition of PKR by vaccinia virus: role of the N- and C-terminal domains of E3L

The process of eukaryotic translation initiation can be regulated by a highly conserved mechanism involving the phosphorylation of the translation initiation factor eIF2 on the α subunit. This mechanism is recognized as an efficient step in the host antiviral response. Vaccinia virus (VV), like many other viruses, encodes proteins to overcome this inhibitory process. The C-terminus of the vaccinia virus E3L is known to bind to double-stranded RNA (dsRNA) thereby sequestering the activator of this antiviral response. In this report, the N-terminus of E3L was found to be required for the additional regulation of eIF2α phosphorylation. This phosphorylation event did not lead to a global shutdown in protein synthesis. Because the N-terminus of E3L is required for full viral pathogenesis in mice, these results suggest an alternative role of eIF2α phosphorylation in regulating viral replication.