Abstract
Latent HSV-1 genomes are chromatinized with silencing marks. Since 2004, however, there has been an apparent inconsistency in the studies of the chromatinization of the HSV-1 genomes in lytically infected cells. Nuclease protection and chromatin immunoprecipitation assays suggested that the genomes were not regularly chromatinized, having only low histone occupancy. However, the chromatin modifications associated with transcribed and non-transcribed HSV-1 genes were those associated with active or repressed transcription, respectively. Moreover, the three critical HSV-1 transcriptional activators all had the capability to induce chromatin remodelling, and interacted with critical chromatin modifying enzymes. Depletion or overexpression of some, but not all, chromatin modifying proteins affected HSV-1 transcription, but often in unexpected manners. Since 2010, it has become clear that both cellular and HSV-1 chromatins are highly dynamic in infected cells. These dynamics reconcile the weak interactions between HSV-1 genomes and chromatin proteins, detected by nuclease protection and chromatin immunoprecipitation, with the proposed regulation of HSV-1 gene expression by chromatin, supported by the marks in the chromatin in the viral genomes and the abilities of the HSV-1 transcription activators to modulate chromatin. It also explains the sometimes unexpected results of interventions to modulate chromatin remodelling activities in infected cells.
Highlights
Herpes simplex virus 1 (HSV-1) establishes lytic infections in most cells, but latent infections in neurons in vivo
Mobilization in U2OS cells in the absence of ICP0 alone even decreased the rate of fast chromatin exchange [98]. These results suggest that VP16 is the primary modulator of H2B fast chromatin exchange, at least under conditions of viral replication
These results suggest that H3.1 is mobilized away from cellular chromatin immediately after infection, but it is assembled into viral chromatin only during HSV-1 DNA replication
Summary
Herpes simplex virus 1 (HSV-1) establishes lytic infections in most cells, but latent infections in neurons in vivo. E proteins replicate HSV-1 DNA, whereas the L genes encode structural and other proteins required for the assembly of infectious virions. The more than 1m of human genomic DNA is packaged within the human nuclei (which are typically ~7 μM in diameter) It regulates DNA accessibility and, all processes requiring access to nuclear DNA. The amino-terminal tails of the core histones are extensively post-translationally modified These PTM provide docking sites for proteins that regulate transcription (the proposed “histone code” [24,25,26,27,28]) and regulate nucleosome stability [29,30]. We will focus on HSV-1 to discuss the recent evidence strongly implicating nucleosome dynamics in the regulation of viral gene expression, and perhaps, DNA replication. These proteins act as (indirect) activators of viral transcription
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