Repression of host RNA polymerase II transcription by herpes simplex virus type 1.
Lytic infection of mammalian cells with herpes simplex virus type 1 (HSV-1) results in rapid repression of host gene expression and selective activation of the viral genome. This transformation in gene expression is thought to involve repression of host transcription and diversion of the host RNA polymerase (RNAP II) transcription machinery to the viral genome. However, the extent of virus-induced host transcription repression and the mechanisms responsible for these major shifts in transcription specificities have not been examined. To determine how HSV-1 accomplishes repression of host RNAP II transcription, we assayed transcription patterns on several cellular genes in cells infected with mutant and wild-type HSV-1. Our results suggest that HSV-1 represses RNAP II transcription on most cellular genes. However, each cellular gene we examined responds differently to the transcription repressive effects of virus infection, both quantitatively and with respect to the involvement of viral gene products. Virus-induced shutoff of host RNAP II transcription requires expression of multiple immediate-early genes. In contrast, expression of delayed-early and late genes and viral DNA replication appear to contribute little to repression of host cell RNAP II transcription. Modification of RNAP II to the intermediately phosphorylated (II(I)) form appears unlinked to virus-induced repression of host cell transcription. However, full repression of host transcription is correlated with depletion of the hyperphosphorylated (IIO) form of RNAP II.
Spencer
C A
CA
Department of Biochemistry, University of Alberta, Edmonton, Canada.
Dahmus
M E
ME
Rice
S A
SA
D002460:Cell Line; D005786:Gene Expression Regulation; D016679:Genome, Viral; D006367:HeLa Cells; D018259:Herpesvirus 1, Human / Q000235:genetics*; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics; D016296:Mutagenesis; D010766:Phosphorylation; D012319:RNA Polymerase II / Q000235:genetics*; D014158:Transcription, Genetic; D044767:Ubiquitin-Protein Ligases; D014764:Viral Proteins; D054334:Viral Regulatory and Accessory Proteins
C057294:ICP22 protein, human herpesvirus 1; D017874:Immediate-Early Proteins; D014764:Viral Proteins; D054334:Viral Regulatory and Accessory Proteins; C048925:herpes simplex virus, type 1 protein ICP4; C078424:EUS1 protein, Equine herpesvirus 1; D044767:Ubiquitin-Protein Ligases; C051804:Vmw110 protein, Human herpesvirus 1; D012319:RNA Polymerase II