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 alpha 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 EM is known to bind to double-stranded RNA (dsRNA) thereby sequestering the activator of this antiviral response. In this report, the N-terminus of EM was found to be required for the additional regulation of eIF2alpha phosphorylation. This phosphorylation event did not lead to a global shutdown in protein synthesis. Because the N-terminus of EM is required for fall viral pathogenesis in mice, these results suggest an alternative role of eIF2alpha phosphorylation in regulating viral replication. (C) 2004 Elsevier Inc. All rights reserved.