title: Genome-wide histone acetylation profiling of Herpesvirus saimiri in human T cells upon induction with a histone deacetylase inhibitor.
abstract: Herpesviruses establish latency in suitable host cells after primary infection and persist in their host organisms for life. Most of the viral genes are silenced during latency, also enabling the virus to escape from an immune response. This study addresses the control of viral gene silencing by epigenetic mechanisms, using Herpesvirus saimiri (HVS) as a model system. Strain C488 of this gamma-2-herpesvirus can transform human T cells to stable growth in vitro, and it persists in the nuclei of those latently infected T cells as a nonintegrating, circular, and histone-associated episome. The whole viral genome was probed for histone acetylation at high resolution by chromatin immunoprecipitation-on-chip (ChIP-on-chip) with a custom tiling microarray. Corresponding to their inactive status in human T cells, the lytic promoters consistently revealed a heterochromatic phenotype. In contrast, the left terminal region of the genome, which encodes the stably expressed oncogenes stpC and tip as well as the herpesvirus U RNAs, was associated with euchromatic histone acetylation marks representing "open" chromatin. Although HVS latency in human T lymphocytes is considered a stable and irreversible state, incubation with the histone deacetylase inhibitor trichostatin A resulted in changes reminiscent of the induction of early lytic replication. However, infectious viral particles were not produced, as the majority of cells went into apoptosis. These data show that epigenetic mechanisms are involved in both rhadinoviral latency and transition into lytic replication.
authors.affiliation: Institut für Klinische und Molekulare Virologie, Friedrich-Alexander Universität Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: Barbara
authors.initials: B
authors.lastname: Alberter
authors.forename: Benjamin
authors.initials: B
authors.lastname: Vogel
authors.forename: Doris
authors.initials: D
authors.lastname: Lengenfelder
authors.forename: Florian
authors.initials: F
authors.lastname: Full
authors.forename: Armin
authors.initials: A
authors.lastname: Ensser
mesh_terms: D000107:Acetylation; D002478:Cells, Cultured; D015967:Gene Expression Regulation, Viral; D006567:Herpesvirus 2, Saimiriine / Q000472:pathogenicity*; D056572:Histone Deacetylase Inhibitors / Q000378:metabolism; D006657:Histones / Q000378:metabolism*; D054884:Host-Pathogen Interactions; D006801:Humans; D013601:T-Lymphocytes / Q000821:virology*; D017735:Virus Latency
chemical_list: D056572:Histone Deacetylase Inhibitors; D006657:Histones