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Epigenotypes of Latent Herpesvirus Genomes

  • J. MinarovitsEmail author
Part of the Current Topics in Microbiology and Immunology book series (CT MICROBIOLOGY, volume 310)

Abstract

Epigenotypes are modified cellular or viral genotypes which differ in transcriptional activity in spite of having an identical (or nearly identical) DNA sequence. Restricted expression of latent, episomal herpesvirus genomes is also due to epigenetic modifications. There is no virus production (lytic viral replication, associated with the expression of all viral genes) in tight latency. In vitro experiments demonstrated that DNA methylation could influence the activity of latent (and/or crucial lytic) promoters of prototype strains belonging to the three herpesvirus subfamilies (α-, β-, and γ-herpesviruses). In vivo, however, DNA methylation is not a major regulator of herpes simplex virus type 1 (HSV-1, a human α-herpesvirus) latent gene expression in neurons of infected mice. In these cells, the promoter/enhancer region of latency-associated transcripts (LATs) is enriched with acetyl histone H3, suggesting that histone modifications may control HSV-1 latency in terminally differentiated, quiescent neurons. Epstein-Barr virus (EBV, a human γ-herpesvirus) is associated with a series of neoplasms. Latent, episomal EBV genomes are subject to host cell-dependent epigenetic modifications (DNA methylation, binding of proteins and protein complexes, histone modifications). The distinct viral epigenotypes are associated with distinct EBV latency types, i.e., cell type-specific usage of latent EBV promoters controlling the expression of latent, growth transformation-associated EBV genes. The contribution of major epigenetic mechanisms to the regulation of latent EBV promoters is variable. DNA methylation contributes to silencing of Wp and Cp (alternative promoters for transcripts coding for the nuclear antigens EBNA 1–6) and LMP1p, LMP2Ap, and LMP2Bp (promoters for transcripts encoding transmembrane proteins). DNA methylation does not control, however, Qp (a promoter for EBNA1 transcripts only) in lymphoblastoid cell lines (LCLs), although in vitro methylated Qp-reporter gene constructs are silenced. The invariably unmethylated Qp is probably switched off by binding of a repressor protein in LCLs.

Keywords

Barr Virus Latent Membrane Protein Herpes Simplex Thymidine Kinase Gene Barr Virus Latent Membrane Protein 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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© Springer-Verlag Berlin Heidelberg 2006

Authors and Affiliations

  1. 1.Microbiological Research GroupNational Center for EpidemiologyBudapestHungary

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