title: Herpes simplex virus alpha protein ICP27 can inhibit or augment viral gene transactivation.
abstract: Three of the five alpha (immediate early) gene products of herpes simplex virus, infected cell proteins (ICPs) 4, 0, and 27 play a role in the control of expression of viral beta (delayed-early) and gamma (late) genes. We report here that ICP27 can inhibit or augment the individual or combined abilities of ICP4 and ICP0 to stimulate expression of chimeric genes containing viral gene promoters in a transient expression system. The specific effect of ICP27 was dependent on the viral gene promoter in the chimeric gene. ICP27 inhibited the ability of ICP4 and ICP0 to activate some beta gene promoters but augmented their ability to activate other beta or gamma 1 gene promoters when they were used in the target genes. Activation of the target genes by adenovirus E1A was not affected by ICP27 under the same conditions. ICP27 also repressed the ability of ICP0 to stimulate expression of a chimeric gene containing an alpha gene promoter. Insertion of a termination codon in the middle of the ICP27 coding region severely reduced the inhibitory effect of the plasmid, indicating that this activity requires expression of functional ICP27 polypeptide. This report focuses on the ICP27 activity that negatively regulates ICP4 transactivation of a chimeric gene containing the upstream sequences of the HSV beta gene ICP8. ICP27 decreased the level of mRNA initiated at the transcriptional start site of the ICP8 gene. The level of expression of the ICP4 gene was not changed by ICP27 but an alteration in the electrophoretic mobility of ICP4 expressed was observed. The modulatory effect of ICP27 on HSV transactivators may control the progress of the lytic cycle or provide a balance that varies in different cell types to affect whether lytic or latent infection ensues.
authors.affiliation: Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, Massachusetts 02115.
authors.forename: L
authors.initials: L
authors.lastname: Su
authors.forename: D M
authors.initials: DM
authors.lastname: Knipe
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002678:Chimera; D005786:Gene Expression Regulation; D017874:Immediate-Early Proteins; D010957:Plasmids; D011401:Promoter Regions, Genetic; D018139:Simplexvirus / Q000235:genetics*; D014709:Vero Cells; D014764:Viral Proteins / Q000235:genetics*
chemical_list: C057120:ICP27 protein, human herpesvirus 1; D017874:Immediate-Early Proteins; D014764:Viral Proteins