title: Simian virus 40 large-T bypasses the translational block imposed by the phosphorylation of elF-2 alpha.
abstract: One of the cellular defense mechanisms against virus infection is mediated by activating the interferon-induced, double-stranded-RNA-activated protein kinase, PKR. Upon activation, PKR phosphorylates and thereby inactivates the protein synthesis initiation factor, elF-2, leading to cessation of protein synthesis. Viruses have evolved diverse strategies to counteract this cellular antiviral response. A majority of these strategies target PKR to prevent its activation. Recently, we showed that simian virus 40 (SV40) large-T antigen reverses PKR-mediated translational inhibition at a step downstream of PKR activation (Rajan et al., J. Virol. 69, 785--795, 1995). In this paper, we present evidence showing that SV40 can restore efficient translation in cells despite the elevated levels of phosphorylated elF-2 alpha resulting from PKR activation. Thus, SV40 large-T-mediated translational rescue occurs at a step downstream of elF-2 alpha phosphorylation.
authors.affiliation: Robert H. Lurie Cancer Center and Microbiology--Immunology Department, Northwestern University Medical School, Chicago, Illinois 60611, USA.
authors.forename: S
authors.initials: S
authors.lastname: Swaminathan
authors.forename: P
authors.initials: P
authors.lastname: Rajan
authors.forename: O
authors.initials: O
authors.lastname: Savinova
authors.forename: R
authors.initials: R
authors.lastname: Jagus
authors.forename: B
authors.initials: B
authors.lastname: Thimmapaya
mesh_terms: D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000378:metabolism*; D002460:Cell Line; D002522:Chlorocebus aethiops; D015852:Eukaryotic Initiation Factor-2 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015967:Gene Expression Regulation, Viral; D010766:Phosphorylation; D014176:Protein Biosynthesis; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D015398:Signal Transduction; D019892:eIF-2 Kinase
chemical_list: D000952:Antigens, Polyomavirus Transforming; D015852:Eukaryotic Initiation Factor-2; D017346:Protein Serine-Threonine Kinases; D019892:eIF-2 Kinase