Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms
ReviewChromatin organization of gammaherpesvirus latent genomes
Introduction
Epstein–Barr virus (EBV) and Kaposi's sarcoma-associated herpesvirus (KSHV) are prototypical members of the human gammaherpesvirus family. These viruses establish long-term latent infection in B-lymphocytes that can lead to lymphoproliferative disorders and cancers, especially in immune-compromised individuals. During latent infection the viral genomes are maintained as circular minichromosomes. The epigenetic modifications and chromatin structure of the viral genome plays a critical role in the establishment and maintenance of latent infection. The gammaherpesvirus genomes have distinct survival strategies that include the ability to replicate and segregate faithfully each cell cycle, similar to a cellular chromosome. The ability of the viral genomes to adopt variant gene expression programs reflects another level of virus–host interactions that integrates cellular growth and differentiation signal with viral gene expression and chromatin organization. Here, we review some of recent experimental findings and emerging concepts that help to understand the epigenetic mechanisms that control gammaherpesvirus latency.
Section snippets
EBV
In latently infected cells, most EBV genomes persist as multicopy nuclear episomes with chromatin structure similar to that of the cellular chromosome (reviewed in [1], [2], [3]). The virus can adopt at least four distinct gene expression patterns that are referred to as latency types [4], [5], [6]. The different latency types correlate with the cellular differentiation state of the host cell or the tumor-type from which the virus has been isolated. In normal memory B-cells, EBV can persist in
KSHV
Kaposi's sarcoma (KS) is among the most prevalent malignancies found in HIV-infected individuals, but can also affect HIV negative individuals in endemic areas [75]. Kaposi's sarcoma-associated herpesvirus (KSHV) has been identified as the causative agent of both HIV-associated and endemic forms of KS [76], [77]. KSHV is also associated with several lymphoproliferative disorders, including primary effusion lymphoma (PELs) and multicentric Castleman's disease [78], [79], [80]. KSHV has many
Acknowledgements
I. Tempera is supported by a fellowship from Instituto Pasteur-Fondazione Cenci Bolognetti, Rome. This work was supported by NIH grants (CA117830, CA093606, and DE017336).
References (159)
- et al.
EBV persistence in memory B cells in vivo
Immunity
(1998) - et al.
The expression pattern of Epstein–Barr virus latent genes in vivo is dependent upon the differentiation stage of the infected B cell
Immunity
(2000) - et al.
Epstein–Barr virus gene expression in oral hairy leukoplakia
Virology
(1993) - et al.
The plasmid replicon of Epstein–Barr virus: mechanistic insights into efficient, licensed, extrachromosomal replication in human cells
Plasmid
(2007) - et al.
Replication from oriP of Epstein–Barr virus requires human ORC and is inhibited by geminin
Cell
(2001) - et al.
The many faces of the origin recognition complex
Curr. Opin. Cell. Biol.
(2007) - et al.
The origin recognition complex functions in sister-chromatid cohesion in Saccharomyces cerevisiae
Cell
(2007) - et al.
Histone acetyltransferase HBO1 interacts with the ORC1 subunit of the human initiator protein
J. Biol. Chem.
(1999) - et al.
Replication factors MCM2 and ORC1 interact with the histone acetyltransferase HBO1
J. Biol. Chem.
(2001) - et al.
Nucleosomes positioned by ORC facilitate the initiation of DNA replication
Mol. Cell
(2001)
EBNA1 efficiently assembles on chromatin containing the Epstein–Barr virus latent origin of replication
Virology
Host cell-dependent expression of latent Epstein–Barr virus genomes: regulation by DNA methylation
Adv. Cancer Res.
DNA methylation and the Epstein–Barr virus
Semin. Cancer Biol.
Viral interactions with the Notch pathway
Semin. Cancer Biol.
CTCF is a uniquely versatile transcription regulator linked to epigenetics and disease
Trends Genet.
Kaposi's sarcoma-associated herpesvirus-like DNA sequences in multicentric Castleman's disease
Blood
The molecular pathology of Kaposi's sarcoma-associated herpesvirus
Biochim. Biophys. Acta
Biology of Kaposi's sarcoma
Euro. J. Cancer
Epstein–Barr virus and its replication
Epstein–Barr virus
Epstein–Barr virus: 40 years on
Nat. Rev. Cancer
Three pathways of Epstein–Barr virus gene activation from EBNA1-positive latency in B lymphocytes
J. Virol.
Replication of Epstein–Barr virus within the epithelial cells of oral “hairy” leukoplakia, an AIDS-associated lesion
N. Engl. J. Med.
Differences in B-cell growth phenotype reflect novel patterns of Epstein–Barr virus latent gene expression in Burkitt's lymphoma cells
EMBO J.
Epstein–Barr virus: exploiting the immune system
Nat. Rev. Immunol.
Epstein–Barr virus exploits BSAP/Pax5 to achieve the B-cell specificity of its growth-transforming program
J. Virol.
Promoter switching in Epstein–Barr virus during the initial stages of infection of B lymphocytes
Proc. Natl. Acad. Sci. U. S. A.
Methylation status of the Epstein–Barr virus (EBV) BamHI W latent cycle promoter and promoter activity: analysis using novel EBV-positive Burkitt and lymphoblastoid cell lines
J. Virol.
Epigenotypes of latent herpesvirus genomes
Curr. Top Microbiol. Immunol.
Differential hyperacetylation of histones H3 and H4 upon promoter-specific recruitment of EBNA2 in Epstein–Barr virus chromatin
J. Virol.
Chromatin profiling of Epstein–Barr virus latency control region
J. Virol.
Dynamic chromatin boundaries delineate a latency control region of Epstein–Barr virus
J. Virol.
Origins of bidirectional replication of Epstein–Barr virus: models for understanding mammalian origins of DNA synthesis
J. Cell. Biochem.
oriP is essential for EBNA gene promoter activity in Epstein–Barr virus-immortalized lymphoblastoid cell lines
J. Virol.
An EBNA-1-dependent enhancer acts from a distance of 10 kilobase pairs to increase expression of the Epstein–Barr virus LMP gene
J. Virol.
A promoter of Epstein–Barr virus that can function during latent infection can be transactivated by EBNA-1, a viral protein required for viral DNA replication during latent infection
J. Virol.
Promoter-proximal regulatory elements involved in oriP-EBNA1-independent and -dependent activation of the Epstein–Barr virus C promoter in B-lymphoid cell lines
J. Virol.
trans activation of an Epstein–Barr viral transcriptional enhancer by the Epstein–Barr viral nuclear antigen 1
Mol. Cell. Biol.
Complex protein–DNA dynamics at the latent origin of DNA replication of Epstein–Barr virus
J. Cell. Sci.
Human origin recognition complex binds to the region of the latent origin of DNA replication of Epstein–Barr virus
EMBO J.
Human DNA replication initiation factors, ORC and MCM, associate with oriP of Epstein–Barr virus
Proc. Natl. Acad. Sci. U. S. A.
The establishment, inheritance, and function of silenced chromatin in Saccharomyces cerevisiae
Annu. Rev. Biochem.
Evidence that protein binding specifies sites of DNA demethylation
Mol. Cell. Biol.
Epstein–Barr virus latency switch in human B-cells: a physico–chemical model
BMC Syst. Biol.
Visualization of DNA replication on individual Epstein–Barr virus episomes
Science (New York, N.Y.)
Plasticity of DNA replication initiation in Epstein–Barr virus episomes
PLoS Biol.
Initiation of DNA replication within oriP is dispensable for stable replication of the latent Epstein–Barr virus chromosome after infection of established cell lines
J. Virol.
Silencing and heritable domains of gene expression
Annu. Rev. Cell. Dev. Biol.
Human Orc2 localizes to centrosomes, centromeres and heterochromatin during chromosome inheritance
EMBO J.
Epstein–Barr nuclear antigen 1 binds and destabilizes nucleosomes at the viral origin of latent DNA replication
Nucleic Acids Res.
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