The first 30 minutes in the life of a virus: unREST in the nucleus.
On entry of viral DNA into cells, a competition ensues between cellular factors that silence viral genes and transcriptional factors that block silencing and transcribe the DNA. In the case of herpes simplex virus 1, the first set of genes expressed after infection-are induced by a viral protein (alphaTIF or VP16). Expression of later (beta,gamma) genes in cells infected at low ratios of virus per cells requires a transcriptional activator (ICP4) that cannot block silencing and a protein, ICP0, hitherto characterized as a promiscuous transactivator. Recent studies indicate that ICP0 blocks silencing of viral DNA by dissociating HDACs 1 and 2 from the CoREST/REST repressor complex. HDACs 1/2 are phosphorylated and translocated to the nucleus. The findings have broad implications regarding silencing of the viral genome during latency and, potentially, the expression of genes encoded by other DNA viruses as well.
Roizman
Bernard
B
Marjorie B. Kovler Viral Oncology Laboratories, The University of Chicago, Chicago, Illinois 60637, USA. Bernard.Roizman@bsd.uchicago.edu
Gu
Haidong
H
Mandel
Gail
G
D002467:Cell Nucleus / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D004267:DNA Viruses; D004279:DNA, Viral; D005091:Exons; D020868:Gene Silencing; D016679:Genome, Viral; D018259:Herpesvirus 1, Human / Q000378:metabolism; D056284:Histone Deacetylase 1; D056464:Histone Deacetylase 2; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D017874:Immediate-Early Proteins / Q000737:chemistry / Q000378:metabolism; D008954:Models, Biological; D009154:Mutation; D009474:Neurons / Q000378:metabolism; D010766:Phosphorylation; D021381:Protein Transport; D012097:Repressor Proteins / Q000378:metabolism; D013997:Time Factors; D015533:Transcriptional Activation; D044767:Ubiquitin-Protein Ligases / Q000737:chemistry
D004279:DNA, Viral; D017874:Immediate-Early Proteins; D012097:Repressor Proteins; C048925:herpes simplex virus, type 1 protein ICP4; D044767:Ubiquitin-Protein Ligases; C051804:Vmw110 protein, Human herpesvirus 1; C110550:HDAC1 protein, human; D056284:Histone Deacetylase 1; D056464:Histone Deacetylase 2; D006655:Histone Deacetylases