SIMIAN-VIRUS-40 LARGE-T BYPASSES THE TRANSLATIONAL BLOCK IMPOSED BY THE PHOSPHORYLATION OF EIF-2-ALPHA

One of the cellular defense mechanisms against virus infection is medi ated by activating the interferon-induced, double-stranded-RNA-activat ed protein kinase, PKR. Upon activation, PKR phosphorylates and thereb y inactivates the protein synthesis initiation factor, eIF-2, leading to cessation of protein synthesis. Viruses have evolved diverse strate gies to counteract this cellular antiviral response. A majority of the se strategies target PKR to prevent its activation. Recently, we showe d that simian virus 40 (SV40) large-T antigen reverses PKR-mediated tr anslational inhibition at a step downstream of PKR activation (Rajan e t al., J. Virol. 69, 785-795, 1995). In this paper, we present evidenc e showing that SV40 can restore efficient translation in cells despite the elevated levels of phosphorylated eIF-2 alpha resulting from PKR activation. Thus, SV40 large-T-mediated translational rescue occurs at a step downstream of eIF-2 alpha phosphorylation. (C) 1996 Academic P ress, Inc.