During lytic infections, herpes simplex virus type 1 DNA is in complexes with the properties of unstable nucleosomes

J Virol. 2010 Feb;84(4):1920-33. doi: 10.1128/JVI.01934-09. Epub 2009 Dec 9.

Abstract

The genomes of herpes simplex virus type 1 (HSV-1) are regularly chromatinized during latency such that their digestion with micrococcal nuclease (MCN) releases nucleosome-sized DNA fragments. In lytically infected cells, in contrast, MCN releases HSV-1 DNA in primarily heterogeneously sized fragments. Consistently, only a small percentage of this HSV-1 DNA coimmunoprecipitates with histones. Most current models propose that histones associate with HSV-1 DNA during lytic infections at low occupancy. However, histone modification or occupation is also proposed to regulate HSV-1 transcription. It remains unclear how the histones associated with a small percentage of HSV-1 DNA may regulate transcription globally. Moreover, the physical properties of the complexes containing histones and HSV-1 DNA are unknown. We evaluated the HSV-1 DNA-containing complexes at 5 h after (lytic) infection by biochemical fractionations. Nuclear HSV-1 DNA did not fractionate as protein-free HSV-1 DNA but as DNA in cellular nucleosomes. Moreover, MCN released HSV-1 DNA in complexes that fractionate as cellular mono- and dinucleosomes by centrifugation followed by sucrose gradients and size-exclusion chromatography. The HSV-1 DNA in such complexes was protected to heterogeneous sizes and was more accessible to MCN than DNA in most cellular chromatin. Using a modified MCN digestion to trap unstable digestion intermediates, HSV-1 DNA was quantitatively recovered in discrete mono- to polynucleosome sizes in complexes fractionating as cellular mono- to polynucleosomes. The HSV-1 DNAs in complexes fractionating as mono- to dinucleosomes were stabilized by cross-linking. Therefore, most HSV-1 DNA forms particularly unstable nucleosome-like complexes at 5 h of lytic infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chlorocebus aethiops
  • Chromatin / metabolism
  • DNA, Viral / chemistry*
  • DNA, Viral / genetics
  • DNA, Viral / metabolism
  • Herpes Simplex / metabolism
  • Herpes Simplex / virology
  • Herpesvirus 1, Human / genetics
  • Herpesvirus 1, Human / pathogenicity*
  • Herpesvirus 1, Human / physiology*
  • Macromolecular Substances
  • Models, Molecular
  • Nucleosomes / metabolism
  • Nucleosomes / virology
  • Vero Cells
  • Virus Replication

Substances

  • Chromatin
  • DNA, Viral
  • Macromolecular Substances
  • Nucleosomes