title: The IE180 protein of pseudorabies virus suppresses phosphorylation of translation initiation factor eIF2α.
abstract: We have previously shown that the porcine alphaherpesvirus pseudorabies virus (PRV) efficiently interferes with phosphorylation of the eukaryotic translation initiation factor eIF2α. Inhibition of phosphorylation of eIF2α has been reported earlier for the closely related alphaherpesvirus herpes simplex virus 1 (HSV-1) through its ICP34.5 and US11 proteins. PRV, however, does not encode an ICP34.5 or US11 orthologue. Assays using cycloheximide, UV-inactivated PRV, or phosphonoacetic acid (PAA) showed that de novo expression of one or more (immediate) early viral protein(s) is required for interference with eIF2α phosphorylation. In line with this, a time course assay showed that eIF2α phosphorylation was abolished within 2 h after PRV inoculation. PRV encodes only one immediate-early protein, IE180, the orthologue of HSV-1 ICP4. As reported earlier, a combinational treatment of cells with cycloheximide and actinomycin D allowed expression of IE180 without detectable expression of the US3 early protein in PRV-infected cells. This led to a substantial reduction in eIF2α phosphorylation levels, indicative for an involvement of IE180. In support of this, transfection of IE180 also potently reduced eIF2α phosphorylation. IE180-mediated interference with eIF2α phosphorylation was not cell type dependent, as it occurred both in rat neuronal 50B11 cells and in swine testicle cells. Inhibition of the cellular phosphatase PP1 impaired PRV-mediated interference with eIF2α phosphorylation, indicating that PP1 is involved in this process. In conclusion, the immediate-early IE180 protein of PRV has the previously uncharacterized ability to suppress phosphorylation levels of the eukaryotic translation initiation factor eIF2α.
authors.affiliation: Department of Virology, Parasitology and Immunology, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.
authors.forename: N
authors.initials: N
authors.lastname: Van Opdenbosch
authors.forename: C
authors.initials: C
authors.lastname: Van den Broeke
authors.forename: N
authors.initials: N
authors.lastname: De Regge
authors.forename: E
authors.initials: E
authors.lastname: Tabarés
authors.forename: H W
authors.initials: HW
authors.lastname: Favoreel
mesh_terms: D000818:Animals; D002460:Cell Line; D015852:Eukaryotic Initiation Factor-2 / Q000378:metabolism*; D011558:Herpesvirus 1, Suid / Q000472:pathogenicity*; D010766:Phosphorylation; D014176:Protein Biosynthesis; D011499:Protein Processing, Post-Translational; D051381:Rats; D013552:Swine; D014764:Viral Proteins / Q000378:metabolism*; D037521:Virulence Factors / Q000378:metabolism*
chemical_list: D015852:Eukaryotic Initiation Factor-2; D014764:Viral Proteins; D037521:Virulence Factors