Histone Modification Pattern of the T-Cellular
            <i>Herpesvirus Saimiri</i>
            Genome in Latency

Alberter, Barbara; Ensser, Armin

doi:10.1128/jvi.01931-06

Cited by 14 publications

(14 citation statements)

References 63 publications

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“…Epigenetic modification patterns of HVS were recently investigated in latently infected T cells. 53 The terminal H-DNA and stpC/tip regions showed an accessible chromatin structure correlating with the transcriptional activity of viral genes during the latency.…”

Section: Discussionmentioning

confidence: 96%

Rhadinovirus vector-derived human telomerase reverse transcriptase expression in primary T cells

2010

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The rhadinovirus herpesvirus saimiri (HVS) as a gene delivery vector allows large DNA insertions and long-termed gene expression. In the case of T-cell transduction, such vectors use the viral transformation-associated genes of HVS C488 for T-cell amplification. In this report, we investigated whether the gene for the catalytic telomerase subunit human telomerase reverse transcriptase (hTERT) can substitute for the transformation-associated genes in rhadinoviral T-cell transduction and amplification. By using virus mutants generated by en passant mutagenesis from bacterial artificial chromosomes, we observed a very early and functional transgene expression even by virus mutants without transformation-associated genes. The markers of T-cell transformation by HVS, namely CD2 hyperreactivity, overexpression of interleukin-26, and of the tyrosine kinase Lyn could neither be induced nor enhanced by ectopic hTERT expression. When the viral transformation-associated genes were replaced by the hTERT gene, it was not sufficient for growth transformation, although hTERT was efficiently transduced and functionally expressed by the rhadinovirus vector. Thus, the transformation-associated proteins StpC and Tip are responsible for the T-cell phenotype after transduction by HVS and, additionally, modulate telomerase activity independently of hTERT expression.

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Section: Discussionmentioning

confidence: 96%

Rhadinovirus vector-derived human telomerase reverse transcriptase expression in primary T cells

2010

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“…The HVS orf73 promoter region has been shown to comprise both heterochromatic and euchromatic histone modification marks (1,2). Therefore, the question arose whether a chromatin border might be located in this region.…”

Section: Resultsmentioning

confidence: 99%

“…The structural organization and modification of viral chromatin is thought to be essential for herpesvirus persistence. We have shown that distinct histone modification patterns are established during HVS latency in transformed human T cells (1,2).…”

Section: Discussionmentioning

confidence: 99%

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The Insulator Protein CTCF Binding Sites in the orf73 /LANA Promoter Region of Herpesvirus Saimiri Are Involved in Conferring Episomal Stability in Latently Infected Human T Cells

Zielke

Full

Teufert

et al. 2012

J Virol

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Herpesviruses establish latency in suitable cells of the host organism after a primary lytic infection. Subgroup C strains of herpesvirus saimiri (HVS), a primate gamma-2 herpesvirus, are able to transform human and other primate T lymphocytes to stable growth in vitro. The viral genomes persist as nonintegrated, circular, and histone-associated episomes in the nuclei of those latently infected T cells. Epigenetic modifications of episomes are essential to restrict the transcription during latency to selected viral genes, such as the viral oncogenes stpC/tip and the orf73/LANA. In this study, we describe a genome-wide chromatin immunoprecipitation-on-chip (ChIP-on-chip) analysis to profile the occupancy of CTCF on the latent HVS genome. We then focused on two distinct, conserved CTCF binding sites (CBS) within the orf73/LANA promoter region. Analysis of recombinant viruses harboring deletions or mutations within the CBS indicated that the lytic replication of such viruses is not substantially influenced by CTCF. However, T cells latently infected with CBS mutants were impaired in their proliferation abilities and showed a significantly reduced episomal maintenance. We detected a reduced transcription of the orf73/LANA gene in the T cells, corresponding to the reduced viral genomes; this might contribute to the loss of HVS episomes, as LANA is central in the maintenance of viral episomes in the dividing T cell populations. These data demonstrate that the episomal stability of HVS genomes in latently infected human T cells is dependent on CTCF.

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“…The modifications could be correlated with the gene expression pattern observed in T cells. Histone acetylation, which is commonly found in context with actively transcribed genes, had previously been investigated with three different antibodies, and investigation revealed that only the H DNA and the latently transcribed stpC/tip promoter were wrapped up with acetylated histones, while the lytic gene promoters, as well as the orf73/lana promoter, remained free of histone acetylation (1). In this study, we sought to generate a detailed view of the histone acetylation status within the complete HVS genome in latency by performing an investigation of a whole herpesviral genome by a ChIP-on-chip experiment.…”

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confidence: 99%

Genome-Wide Histone Acetylation Profiling of Herpesvirus saimiri in Human T Cells upon Induction with a Histone Deacetylase Inhibitor

Alberter

Vogel

Lengenfelder

et al. 2011

J Virol

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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.

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Histone Modification Pattern of the T-Cellular Herpesvirus Saimiri Genome in Latency

Cited by 14 publications

References 63 publications

Rhadinovirus vector-derived human telomerase reverse transcriptase expression in primary T cells

Rhadinovirus vector-derived human telomerase reverse transcriptase expression in primary T cells

The Insulator Protein CTCF Binding Sites in the orf73 /LANA Promoter Region of Herpesvirus Saimiri Are Involved in Conferring Episomal Stability in Latently Infected Human T Cells

Genome-Wide Histone Acetylation Profiling of Herpesvirus saimiri in Human T Cells upon Induction with a Histone Deacetylase Inhibitor

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