title: Checkpoints in productive and latent infections with herpes simplex virus 1: conceptualization of the issues.
abstract: The fundamental question posed here is why in dorsal root ganglia herpes simplex viruses (HSV) can establish a silent infection in which only latency associate transcripts (LAT) and miRNAs are expressed and the neuronal cell survives whereas in non-neuronal cells HSV replicates and destroys the infected cells. Current evidence indicates that in productive infection there are two checkpoints. The first is at activation of α genes and requires a viral protein (VP16) that recruits HCF-1, Oct1, LSD1, and the CLOCK histone acetyl transferase to demethylate histones and initiate transcription. The second checkpoint involves activation of β and γ genes. An α protein, ICP0, activates transcription by displacing HDAC1 or 2 from the HDAC/CoREST/LSD1/REST repressor complex at its DNA binding sites. Current data suggest that in dorsal root ganglia VP16 and HCF-1 are not translocated to neuronal nucleus and that the HDAC/CoREST/LSD1/REST complex is not suppressed-a first step in silencing of the viral genome and establishment of heterochromatin. The viral genome remains in a state of equilibrium with respect to viral gene expression. The function of both LAT and the micro RNAs is to silence low level expression of viral genes that could reactivate the latent genomes.
authors: Marjorie B. Kovler Viral Oncology Laboratories, The University of Chicago, 910 East 58th Street, Chicago, IL 60637, USA. bernard.roizman@bsd.uchicago.edu
authors: Bernard
authors: B
authors: Roizman
authors: Guoying
authors: G
authors: Zhou
authors: Te
authors: T
authors: Du
mesh_terms: D000818:Animals; D005727:Ganglia, Spinal / Q000821:virology*; D015967:Gene Expression Regulation, Viral; D006561:Herpes Simplex / Q000821:virology*; D018259:Herpesvirus 1, Human / Q000235:genetics*; D006570:Heterochromatin / Q000235:genetics / Q000378:metabolism; D056466:Histone Demethylases / Q000235:genetics / Q000378:metabolism; D006657:Histones / Q000235:genetics / Q000378:metabolism; D051863:Host Cell Factor C1 / Q000235:genetics / Q000378:metabolism; D054884:Host-Pathogen Interactions; D006801:Humans; D051379:Mice; D050810:Octamer Transcription Factors / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*; D017735:Virus Latency / Q000502:physiology*
chemical_list: C497692:HCFC1 protein, human; D006570:Heterochromatin; D006657:Histones; D051863:Host Cell Factor C1; D050810:Octamer Transcription Factors; C484169:POU2F3 protein, human; D012097:Repressor Proteins; D014764:Viral Proteins; D056466:Histone Demethylases; C495195:KDM1A protein, human