Components of the REST/CoREST/histone deacetylase repressor complex are disrupted, modified, and translocated in HSV-1-infected cells.
The infected cell protein (ICP)0 enables gene expression and the replication of herpes simplex virus (HSV)-1 in cells infected at low multiplicities and enhances the expression of genes introduced into cells by transfection or infection. We report that a short sequence of ICP0 is similar to a sequence in the amino terminus of CoREST, a corepressor that exists in complexes with the repressor REST and histone deacetylases (HDACs) 1 or 2 to repress cellular gene expression. In wild-type-virus-infected cells, HDAC1 dissociates from the CoREST/REST complex, CoREST and HDAC1 are phosphorylated by a process mediated by viral protein kinases, and CoREST and HDAC1 are partially translocated to the cytoplasm. In cells infected with a virus mutant (DeltaICP4), in which ICP0 accumulates, but post-alpha gene expression is blocked, HDAC1 is dissociated from the CoREST/REST complex, but translocation to the cytoplasm does not occur. After infection with a mutant virus from which ICP0 is deleted, the complex remains intact, but, under conditions of productive infection, the complex is partially translocated to the cytoplasm. These results suggest that, at low multiplicities of infection, ICP0 blocks CoREST-mediated silencing of viral genes by dissociation of HDAC1, whereas subsequent modifications and translocation of the components of the complex are the functions of other viral gene products made later in infection.
Gu
Haidong
H
Marjorie B. Kovler Viral Oncology Laboratories, University of Chicago, Chicago, IL 60637, USA.
Liang
Yu
Y
Mandel
Gail
G
Roizman
Bernard
B
D002458:Cell Fractionation; D002460:Cell Line; D056970:Co-Repressor Proteins; D004268:DNA-Binding Proteins / Q000378:metabolism* / Q000502:physiology; D015967:Gene Expression Regulation, Viral; D018259:Herpesvirus 1, Human; D056284:Histone Deacetylase 1; D006655:Histone Deacetylases / Q000378:metabolism / Q000502:physiology; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics* / Q000378:metabolism; D015151:Immunoblotting; D047468:Immunoprecipitation; D018613:Microscopy, Confocal; D046912:Multiprotein Complexes / Q000378:metabolism* / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000378:metabolism* / Q000502:physiology; D010766:Phosphorylation; D021381:Protein Transport / Q000502:physiology; D012097:Repressor Proteins / Q000378:metabolism* / Q000502:physiology; D014157:Transcription Factors / Q000378:metabolism / Q000502:physiology; D044767:Ubiquitin-Protein Ligases; D000099229:RE1-Silencing Transcription Factor
D056970:Co-Repressor Proteins; D004268:DNA-Binding Proteins; D056284:Histone Deacetylase 1; D006655:Histone Deacetylases; D017874:Immediate-Early Proteins; D046912:Multiprotein Complexes; D009419:Nerve Tissue Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; D044767:Ubiquitin-Protein Ligases; D000099229:RE1-Silencing Transcription Factor; C121019:RCOR1 protein, human; C051804:Vmw110 protein, Human herpesvirus 1; C110550:HDAC1 protein, human