Skip to main content
SpringerLink
Log in
Book cover

DNA Methylation: Development, Genetic Disease and Cancer pp 61–80Cite as

Epigenotypes of Latent Herpesvirus Genomes

  • Chapter

Part of the book series: Current Topics in Microbiology and Immunology ((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.

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   129.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Adam GIR, Cui H, Miller SJ, Flam F, Ohlsson R (1996) Allele-specific in situ hybridization (ASISH) analysis: a novel technique which resolves differential usage of H19 within the same cell lineage during human placental development. Development 122:839–847

    PubMed  CAS  Google Scholar 

  • Adams A, Lindahl T (1975) Epstein-Barr virus genomes with properties of circular DNA molecules in carrier cells. Proc Natl Acad Sci USA 72:1477–1481

    Article  PubMed  CAS  Google Scholar 

  • Alcobia I, Dilao R, Parreira L (2000) Spatial associations of centromers in the nuclei of hematopoietic cells: evidence for cell-type-specific organizational patterns. Blood 95:1608–1615

    PubMed  CAS  Google Scholar 

  • Altiok E, Minarovits J, Hu LF, Contreras-Brodin B, Klein G, Ernberg I (1992) Host-cell-phenotype-dependent control of BCR2/BWR1 promoter complex regulates the expression of Epstein-Barr virus antigens 2–6. Proc Natl Acad Sci USA 89:905–909

    Article  PubMed  CAS  Google Scholar 

  • Arthur JL, Scarpini CG, Connor V, Lachmann RH, Tolkowsky AM, Efstathiou S (2001) Herpes simplex virus type 1 promoter activity during latency establishment, maintenance, and reactivation in primary dorsal root neurons in vitro. J Virol 75:3885–3895

    Article  PubMed  CAS  Google Scholar 

  • Bednarik DP (1996) The silencing of human immunodeficiency virus. In: Russo EA, Martienssen RA, Riggs AD (eds) Epigenetic mechanisms of gene regulation. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, pp 547–559

    Google Scholar 

  • Bhende P, Seaman W, Delecluse HJ, Kenney SC (2004) The EBV lytic switch protein Z, preferentially binds to and activates the methylated viral genome. Nat Genet 36:1099–1104

    Article  PubMed  CAS  Google Scholar 

  • Brooks AR, Harkins RN, Wang P, Qian HS, Liu P, Rubanyi GM (2004) Transcriptional silencing is associated with extensive methylation of the CMV promoter following adenoviral gene delivery to muscle. J Gene Med 6:395–404

    Article  PubMed  CAS  Google Scholar 

  • Brown KE, Guest SS, Smale ST, Hahm K, Merkenschlager M, Fischer A (1997) Association of transcriptionally silent genes with Ikaros complexes at centromeric heterochromatin. Cell 91:845–854

    Article  PubMed  CAS  Google Scholar 

  • Buschhausen G, Graessmann M, Graessmann A (1985) Inhibition of herpes simplex thymidine kinase gene expression by DNA methylation is an indirect effect. Nucleic Acids Res 13:5503–5513

    PubMed  CAS  Google Scholar 

  • Buschhausen G, Wittig B, Graessmann M, Graessmann A (1987) Chromatin structure is required to block transcription of the methylated herpes simplex thymidine kinase gene. Proc Natl Acad Sci USA 84:1177–1181

    Article  PubMed  CAS  Google Scholar 

  • Chau CM, Lieberman PM (2004) Dynamic chromatin boundaries delineate a latency control region of Epstein-Barr virus. J Virol 78:12308–12319

    Article  PubMed  CAS  Google Scholar 

  • Chen F, Hu LF, Ernberg I, Klein G, Winberg G (1995) Coupled transcription of Epstein-Barr virus latent membrane protein (LMP)-1 and LMP2-B genes in nasopharyngeal carcinomas. J Gen Virol 76:131–138

    PubMed  CAS  Google Scholar 

  • Chen HL, Lung MM, Sham JS, Choy DT, Griffin BE, Ng MH (1992) Transcription of BamHI-A region of the EBV genome in NPC tissues and B cells. Virology 191:193–201

    Article  PubMed  CAS  Google Scholar 

  • Chen J, Ueda K, Sakakibara S, Okuno T, Parravicini C, Corbellino M, Yamanishi K (2001) Activation of latent Kaposi’s sarcoma-associated herpesvirus by demethylation of the promoter of the lytic transactivator. Proc Natl Acad Sci USA 98:4119–4124

    Article  PubMed  CAS  Google Scholar 

  • Christy B, Scangos G (1982) Expression of transfected thymidine kinase genes is controlled by methylation. Proc Natl Acad Sci USA 79:6299–6303

    Article  PubMed  CAS  Google Scholar 

  • Contreras-Brodin BA, Anvret M, Imreh S, Altiok E, Klein G, Masucci MG (1991) Bcellphenotype-dependent expression of the Epstein-Barrvirus nuclear antigens EBNA2-to EBNA-6: studies with somatic cell hybrids. J Gen Virol 72:3025–3033

    PubMed  CAS  Google Scholar 

  • de Jesus O, Smith PR, Spender LC, Karstegl CE, Niller HH, Huang D, Farrell PJ (2003) Updated Epstein-Barr virus (EBV) DNA sequence and analysis of a promoter for the BART (CST, BARF0) RNAs of EBV. J Gen Virol 84:1443–1450

    Article  PubMed  CAS  Google Scholar 

  • Decaussin G, Sbih-Lammali F, de Turenne-Tessier M, Bouguermouh A, Ooka T (2000) Expression of BARF 1 gene encoded by Epstein-Barr virus in nasopharyngeal carcinoma biopsies. Cancer Res 60:5584–5588

    PubMed  CAS  Google Scholar 

  • Deshamne SL, Fraser NW (1989) During latency, herpes simplex virus type 1 DNA is associated with nucleosomes in a chromatin structure. J Virol 63:943–947

    Google Scholar 

  • Desrosiers RC (1982) Specifically unmethylated cytidylic-guanylate sites in herpesvirus saimiri DNA in tumor cells. J Virol 43:427–435

    PubMed  CAS  Google Scholar 

  • Desrosiers RC, Mulder C, Fleckenstein B (1979) Methylation of herpesvirus saimiri DNA in lymphoid tumor cell lines. Proc Natl Acad Sci USA 76:3839–3843

    Article  PubMed  CAS  Google Scholar 

  • Dobson AT, Sedarati F, Devi-Rao G, Flanagan WM, Farrell MJ, Stevens JG, Wagner EK, Feldman LT (1989) Identification of the latency-associated transcript promoter by expression of beta-globin mRNA in mouse sensory nerve ganglia latently infected with a recombinant herpes simplex virus. J Virol 63:3844–3851

    PubMed  CAS  Google Scholar 

  • Dressler GR, Rock DL, Fraser NW (1987) Latent herpes simplex virus type I DNA is not extensively methylated in vivo. J Gen Virol 68:1761–1765

    PubMed  CAS  Google Scholar 

  • Egger G, Liang G, Jones P (2004) Epigenetics in human disease and prospects for epigenetic therapy. Nature 429:457–463

    Article  PubMed  CAS  Google Scholar 

  • Ehrlich M (2003) Expression of various genes is controlled by DNA methylation during mammalian development. J Cell Biochem 88:899–910

    Article  PubMed  CAS  Google Scholar 

  • Elliott J, Goodhew EB, Krug LT, Shakhnovsky N, Yoo L, Speck SH (2004) Variable methylation of the Epstein-Barr virus Wp EBNA gene promoter in B-lymphoblastoid cell lines. J Virol 78:14602–14605

    Google Scholar 

  • Falk KI, Szekely L, Aleman A, Ernberg I (1998) Specific methylation patterns in two control regions of Epstein-Barr virus latency: the LMP1-coding upstream regulatory region and an origin of DNA replication (oriP). J Virol 72:2969–2974

    PubMed  CAS  Google Scholar 

  • Forejt J, Saam JR, Gregorova S, Tilgham SM (1999) Monoallelic expression of reactivated imprinted genes in embryonal carcinoma cell hybrids. Exp Cell Res 252:416–422

    Article  PubMed  CAS  Google Scholar 

  • Frommer M, McDonald LE, Millar DS, Collis CM, Watt F, Grigg GW, Molloy PL, Paul CL (1992) A genomic sequencing protocol that yields a positive display of 5-methylcytosine residues in individual DNA strands. Proc Natl Acad Sci USA 89:1827–1831

    Article  PubMed  CAS  Google Scholar 

  • Honess RW, Gompels UA, Barrell BG, Craxton M, Cameron KR, Staden R, Chang YN, Hayward GS (1989) Deviations from expected frequencies of CpG dinucleotides in herpesvirus DNAs may be diagnostic of differences in the states of their latent genomes. J Gen Virol 70:837–855

    PubMed  CAS  Google Scholar 

  • Hu LF, Minarovits J, Contreras-Salazar B, Rymo L, Falk K, Klein G, Ernberg I (1991) Variable expression of latent membrane protein in nasopharyngeal carcinoma can be related to methylation status of the Epstein-Barr virus BNLF-1 5′ flanking region. J Virol 65:1558–1567

    PubMed  CAS  Google Scholar 

  • Imai S, Koizumi S, Sugiura M, Tokunaga M, Uemura Y, Yamamoto N, Tanaka S, Sato E, Osato T (1994) Gastric carcinoma: monoclonal epithelial malignant cells expressing Epstein-Barr virus latent infection protein. Proc Natl Acad Sci USA 91:9131–9135

    Article  PubMed  CAS  Google Scholar 

  • Jaenisch R, Schnieke A, Harbers K (1985) Treatment of mice with 5-azacytidine activates silent retroviral genomes in different tissues. Proc Natl Acad Sci USA 82:1451–1455

    Article  PubMed  CAS  Google Scholar 

  • Jankelevich S, Kolman JL, Bodnar JW, Miller G (1992) A nuclear attachment region organizes the Epstein-Barr viral plasmid in Raji cells into a single DNA domain. EMBO J 11:1165–1176

    PubMed  CAS  Google Scholar 

  • Jansson A, Masucci M, Rymo L (1992) Methylation at discrete sites within the enhancer region regulate the activity of the Epstein-Barrvirus BamJI W promoter in Burkitt lymphoma lines. J Virol 66:62–69

    PubMed  CAS  Google Scholar 

  • Jenuwein T, Allis CD (2001) Translating the histone code. Science 293:2889–2897

    Article  Google Scholar 

  • Jin XW, Speck SH (1992) Identification of critical cis elements involved in mediating Epstein-Barr virus nuclear antigen 2-dependent activity of an enhancer located upstream of the viral BamHI C promoter. J Virol 66:2846–2852

    PubMed  CAS  Google Scholar 

  • Kanamori A, Ikuta K, Shigeharu U, Kato S, Hirai K (1987) Methylation of Marek’s disease virus DNA in chicken T-lymphoblastoid cell lines. J Gen Virol 68:1485–1490

    PubMed  CAS  Google Scholar 

  • Kerr BM, Lear AL, Rowe M, Croom-Carter D, Young LS, Rookes S, Gallimore PH, Rickinson AB (1992) Three transcriptionally distinct forms of Epstein-Barr virus latency in somatic cell hybrids: cell phenotype dependence of promoter usage. Virology 187:189–201

    Article  PubMed  CAS  Google Scholar 

  • Klein G (1996) EBV-B cell interactions: immortalization, rescue from apoptosis, tumorigenicity. Acta Microbiol Immunol Hung 43:97–105

    PubMed  CAS  Google Scholar 

  • Kosak ST, Skok JA, Medina KL, Riblet R, Le Beau MM, Fischer AG, Singh H (2002) Subnuclear compartmentalization of immunoglobulin loci during lymphocyte development. Science 296:158–162

    Article  PubMed  CAS  Google Scholar 

  • Kubat NJ, Tran RK, McAnany P, Bloom DC (2004a) Specific histone tail modification and not DNA methylation is a determinant of herpes simplex virus type 1 latent gene expression. J Virol 78:1139–1149

    Article  PubMed  CAS  Google Scholar 

  • Kubat NJ, Amelio AL, Giordani NV, Bloom DC (2004b) The herpes simplex virus type 1 latency-associated transcript (LAT) enhancer/rcr is hyperacetylated during latency independently of LAT transcription. J Virol 78:12508–12518

    Article  PubMed  CAS  Google Scholar 

  • Levine SS, King IF, Kingston RE (2004) Division of labour in Polycomb group repression. Trends Biochem Sci 29:479–485

    Article  CAS  Google Scholar 

  • Li H, Minarovits J (2003) Host cell-dependent expression of latent Epstein-Barr virus genomes: regulation by DNA methylation. Adv Cancer Res 89:133–156

    Article  PubMed  CAS  Google Scholar 

  • Li Q, Peterson KR, Fang X, Stamatoyannopoulos G (2002) Locus control regions. Blood 100:3077–3086

    Article  PubMed  CAS  Google Scholar 

  • Liebowitz D (1998) Pathogenesis of Epstein-Barr virus. In: McCance DJ (ed) Human tumor viruses. ASM Press, Washington, pp 175–199

    Google Scholar 

  • Ling PD, Hsieh JD, Ruf IK, Rawlins DE, Hayward SD (1994) EBNA-2 upregulation of Epstein-Barr virus promoters and the cellular CD23 promoter utilizes a common targeting intermediate, CBF1. J Virol 68:5375–5383

    PubMed  CAS  Google Scholar 

  • Lokensgard JR, Bloom DC, Dobson AT, Feldman LT (1994) Long-term promoter activity during herpes simplex virus latency. J Virol 68:7148–7158

    PubMed  CAS  Google Scholar 

  • Longnecker R (1998) Molecular biology of Epstein-Barr virus. In: McCance DJ (ed) Human tumor viruses. ASM Press, Washington, pp 135–174

    Google Scholar 

  • Masucci MG, Contreras-Salazar B, Ragnar E, Falk K, Minarovits J, Ernberg I, Klein G (1989) 5-Azacytidine up regulates the expression of Epstein-Barr virus nuclear antigen 2 (EBNA-2) through EBNA-6 and latentmembrane protein in the Burkitt’s lymphoma line Rael. J Virol 63:3135–3141

    PubMed  CAS  Google Scholar 

  • McGeoch DJ, Davison AJ (1999) The molecular history of herpesviruses. In: Domingo E, Webster R, Holland J (eds) Origin and evolution of viruses. Academic Press, New York, pp 441–465

    Google Scholar 

  • Mellerick DM, Fraser NW (1987) Physical state of the latent herpes simplex virus genomein amousemodel system: evidence suggesting an episomal state. Virology 158:265–275

    Article  PubMed  CAS  Google Scholar 

  • Minarovits J, Minarovits-Kormuta S, Ehlin-Henriksson B, Falk K, Klein G, Ernberg I (1991) Host cell phenotype-dependent methylation patterns of Epstein-Barr virus DNA. J Gen Virol 72:1591–1599

    PubMed  CAS  Google Scholar 

  • Minarovits J, Hu LF, Marcsek Z, Minarovits-Kormuta S, Klein G, Ernberg I (1992) RNA polymerase III-transcribed EBER 1 and 2 transcription units are expressed and hypomethylated in the major Epstein-Barr virus carrying cell types. J Gen Virol 73:1687–1692

    PubMed  CAS  Google Scholar 

  • Minarovits J, Hu LF, Imai S, Harabuchi Y, Kataura A, Minarovits-Kormuta S, Osato T, Klein G (1994) Clonality, expression and methylation patterns of the Epstein-Barr virus genomes in lethal midline granulomas classified as peripheral angiocentric T cell lymphomas. J Gen Virol 75:77–84

    PubMed  CAS  Google Scholar 

  • Mitsuya K, Sui H, Meguro M, Kugoh H, Jinno Y, Niikawa N, Oshimura M (1997) Paternal expression of WT1 in human fibroblasts and lymphocytes. Hum Mol Genet 6:2243–2246

    Article  PubMed  CAS  Google Scholar 

  • Morimura T, Ohashi K, Sugimoto C, Onuma M (1998) Pathogenesis of Marek’s disease (MD) and possible mechanism of immunity induced by MD vaccine. J Vet Med Sci 60:1–8

    Article  PubMed  CAS  Google Scholar 

  • Niller HH, Salamon D, Takacs M, Uhlig J, Wolf H, Minarovits J (2001) Protein-DNA interaction and CpG methylation at rep*/vIL-10p of latent Epstein-Barr virus genomes in lymphoid cell lines. Biol Chem 382:1411–1419

    Article  PubMed  CAS  Google Scholar 

  • Niller HH, Salamon D, Ilg K, Koroknai A, Banati F, Bäml G, Rücker OL, Schwarzmann F, Wolf H, Minarovits J (2003) The in vivo binding site for oncoprotein c-Myc in the promoter for Epstein-Barr virus (EBV) encoding RNA (EBER) 1 suggests a specific role for EBV in lymphomagenesis. Med Sci Monit 9:HY1–HY9

    PubMed  CAS  Google Scholar 

  • Niller HH, Salamon D, Rahmann S, Ilg K, Koroknai A, Bánáti F, Schwarzmann F, Wolf H, Minarovits J (2004a) A 30 kb region of the Epstein-Barr virus genome is colinear with the rearranged human immunoglobulin gene loci: implications for a “ping-pong evolution” model for persisting viruses and their hosts. Acta Microbiol Immunol Hung 51:469–484

    Article  PubMed  CAS  Google Scholar 

  • Niller HH, Salamon D, Banati F, Schwarzmann F, Wolf H, Minarovits J (2004b) The LCR of EBV makes Burkitt’s lymphoma endemic. Trends Microbiol 12:495–499

    Article  PubMed  CAS  Google Scholar 

  • Niller HH, Salamon D, Ilg K, Koroknai A, Banati F, Schwarzmann F, Wolf H, Minarovits J (2004c) EBV-associated neoplasms: alternative pathogenetic pathways. Med Hypotheses 62:387–391

    Article  PubMed  CAS  Google Scholar 

  • Nonoyama M, Pagano JS (1972) Separation of Epstein-Barr virus DNA from large chromosomal DNA in non-virus producing cells. Nature 238:169–171

    Article  CAS  Google Scholar 

  • Obata Y, Kono T (2002) Maternal primary imprinting is established at a specific time for each gene throughout oocyte growth. J Biol Chem 277:5285–5289

    Article  PubMed  CAS  Google Scholar 

  • Prosch S, Stein J, Staak K, Liebenthal C, Volk HD, Kruger DH (1996) Inactivation of the very strong HCMV immediate early promoter by CpG methylation in vitro. Biol Chem Hoppe Seyler 377:195–201

    PubMed  CAS  Google Scholar 

  • Robertson KD, Hayward SD, Ling PD, Samid D, Ambinder R (1995) Transcriptional activation of the Epstein-Barr virus latency C promoter after 5-azacytidine treatment: evidence that demethylation at a single CpG site is crucial. Mol Cell Biol 15:6150–6159

    PubMed  CAS  Google Scholar 

  • Sadler RH, Raab-Traub N (1995) The Epstein-Barr virus 3.5-kilobase latent membrane protein mRNA initiates from a TATA-less promoter within the first terminal repeat. J Virol 69:4577–4581

    PubMed  CAS  Google Scholar 

  • Saitoh S, Buiting K, Rogan PK, Buxton JL, Driscoll DJ, Arnemann J, König R, Malcolm S, Horsthemke B (1996) Minimal definition of the imprinting center and fixation of a chromosome 15q11-13 epigenotype by imprinting mutations. Proc Natl Acad Sci USA 93:7811–7815

    Article  PubMed  CAS  Google Scholar 

  • Salamon D, Takacs M, Myöhänen S, Marcsek Z, Berencsi G, Minarovits J (2000) De novo methylation at nonrandom founder sites 5′ from an unmethylated minimal origin of DNA replication in latent Epstein-Barr virus genomes. Biol Chem 381:95–105

    Article  PubMed  CAS  Google Scholar 

  • Salamon D, Takacs M, Ujvari D Uhlig J, Wolf H, Minarovits J, Niller HH (2001) Protein-DNA binding and CpG methylation at nucleotide resolution of latency-associated promoters Qp, Cp and LMP1p of Epstein-Barr virus. J Virol 75:2584–2596

    Article  PubMed  CAS  Google Scholar 

  • Salamon D, Takacs M, Schwarzmann F, Wolf H, Minarovits J, Niller HH (2003) High-resolution methylation analysis and in vivo protein-DNA binding at the promoter of the viral oncogene LMP2A in B cell lines carrying latent Epstein-Barr virus genomes. Virus Genes 27:57–66

    Article  PubMed  CAS  Google Scholar 

  • Sano M, Kitayama S (1996) Inhibition of nerve growth factor-induced outgrowth of neurites by trichostatin A requires de novo protein synthesis in PC12D cells. Brain Res 742:195–202

    Article  PubMed  CAS  Google Scholar 

  • Santoso B, Ortiz BD, Winoto A (2000) Control of organ-specific demethylation by an element of the T-cell receptor-α locus control region. J Biol Chem 275:1952–1958

    Article  PubMed  CAS  Google Scholar 

  • Schaefer BC, Strominger JL, Speck SH (1997) Host-cell-determined methylation of specific Epstein-Barr virus promoters regulates the choice between distinct viral latency programs. Mol Cell Biol 17:364–377

    PubMed  CAS  Google Scholar 

  • Sjöblom-Hallén A, Yang W, Jansson A, Rymo L (1999) Silencing the Epstein-Barr virus latent membrane protein 1 gene by the Max-Mad1-mSin3A modulator of chromatin structure. J Virol 73:2983–2993

    PubMed  Google Scholar 

  • Stevens JG, Wagner EK, Devi-Rao GB, Cook ML, Feldman LT (1987) RNA complementary to a herpesvirus alpha gene mRNA prominent in latently infected neurons. Science 235:1056–1059

    PubMed  CAS  Google Scholar 

  • Strockbine LD, Cohen JI, Farrah T, Lyman SD, Wagener F, DuBose R, Armitage SJ, Spriggs MK (1998) The Epstein-Barr virus BARF1 gene encodes a novel, soluble colony-stimulating factor-1 receptor. J Virol 72:4015–4021

    PubMed  CAS  Google Scholar 

  • Su A, Wiltshire T, Batalov S, Lapp H, Ching K, Block D, Zhang J, Soden R, Hayakawa M, Kreiman G, Cooke M, Walker JR, Hogenesch JB (2004) A gene atlas of the mouse and human protein-encoding transcriptomes. Proc Natl Acad Sci USA 101:6062–6067

    Article  PubMed  CAS  Google Scholar 

  • Sung NS, Kenney S, Gutsch D, Pagano JS (1991) EBNA-2 transactivates a lymphoid specific enhancer in the BamHI-Cpromoter of Epstein-Barr virus. J Virol 65:2164–2169

    PubMed  CAS  Google Scholar 

  • Sutter D, Doerfler W (1980) Methylation of integrated adenovirus type 12 DNA sequences in transformed cells is inversely correlated with gene expression. Proc Natl Acad Sci USA 77:253–256

    Article  PubMed  CAS  Google Scholar 

  • Takacs M, Myöhänen S, Altiok E, Minarovits J (1998) Analysis of methylation patterns in the regulatory region of the latent Epstein-Barr virus promoter BCR2 by automated fluorescent genomic sequencing. Biol Chem 379:417–422

    Article  PubMed  CAS  Google Scholar 

  • Takacs M, Salamon D, Myöhänen S, Li H, Segesdi J, Ujvari D, Uhlig J, Niller HH, Wolf H, Berencsi G, Minarovits J (2001a) Epigenetics of latent Epstein-Barr virus genomes: high resolution methylation analysis of the bidirectional promoter region of latent membrane protein 1 and 2B genes. Biol Chem 382:699–705

    Article  PubMed  CAS  Google Scholar 

  • Takacs M, Segesdi J, Balog K, Mezei M, Tóth G, Minárovits J (2001b) Relative deficiency in CpG dinucleotides is a widespread but not unique feature of Gammaherpesvirinae genomes. Acta Microbiol Immunol Hung 48:349–357

    Article  PubMed  CAS  Google Scholar 

  • Tao Q, Robertson KD, Manns A, Hildesheim A, Ambinder RF (1998) The Epstein-Barr virus latent promoter Q is constitutively active, hypomethylated and methylation sensitive. J Virol 72:7075–7083

    PubMed  CAS  Google Scholar 

  • Tao Q, Huang H, Geiman TM, Lim CY, Fu L, Qiu GH, Robertson KD (2002) Defective de novo methylation of viral and cellular DNA sequences in ICF syndrome cells. Hum Mol Genet 11:2091–9102

    Article  PubMed  CAS  Google Scholar 

  • Tasseron-de Jong JG, den Dulk H, van de Putte P, Giphart-Gassler M (1989) De novo methylation is a major event in the inactivation of transfected herpesvirus thymidine kinase genes in human cells. Biochim Biophys Acta 1007:215–223

    PubMed  CAS  Google Scholar 

  • Tierney RJ, Kirby HE, Nagra JK, Desmond J, Bell AI, Rickinson AB (2000) Methylation of transcription factor binding sites in the Epstein-Barr virus latent cycle promoter Wp coincides with promoter downregulation during virus-induced B-cell transformation. J Virol 74:10468–10479

    Article  PubMed  CAS  Google Scholar 

  • Toth M, Muller U, Doerfler W (1990) Establishment of de novo DNA methylation patterns. Transcription factor binding and non-CpG sequences in an integrated adenovirus promoter. J Mol Biol 214:673–683

    Article  PubMed  CAS  Google Scholar 

  • Vardimon L, Newmann R, Kuhlmann I, Sutter D, Doerfler W (1980) DNA methylation and viral gene expression in adenovirus transformed and infected cells. Nucleic Acids Res 8:2461–2473

    PubMed  CAS  Google Scholar 

  • Welch HM, Bridges CG, Lyon AM, Griffiths L, Edington N (1992) Latent equid herpesviruses 1 and 4: detection and distinction using the polymerase chain reaction and co-cultivation from lymphoid tissues. J Gen Virol 73:261–268

    Article  PubMed  CAS  Google Scholar 

  • Wettstein FO, Stevens JG (1983) Shope papilloma virus DNA is extensively methylated in non-virus-producing neoplasms. Virology 126:493–504

    PubMed  CAS  Google Scholar 

  • Whitelaw E, Martin DIK (2001) Retrotransposons as epigenetic mediators of phenotypic variation in mammals. Nat Genet 27:361–365

    Article  PubMed  CAS  Google Scholar 

  • Woisetschlaeger M, Yandava C, Fumarsky L, Strominger J, Speck S (1990) Promoterswitching in Epstein-Barr virus during the initial infection in B lymphocytes. Proc Natl Acad Sci USA 87:1725–1729

    Article  PubMed  CAS  Google Scholar 

  • Wolffe AP, Matzke MA (1999) Epigenetics: regulation through repression. Science 286:481–486

    Article  PubMed  CAS  Google Scholar 

  • Yoshioka M, Kikuta H, Ishiguro N, Ma X, Kobayashi K (2003a) Unique Epstein-Barr virus (EBV) latent gene expression, EBNA promoter usage and EBNA promoter methylation status in chronic active EBV infection. J Gen Virol 84:1133–1140

    Article  PubMed  CAS  Google Scholar 

  • Yoshioka M, Kikuta H, Ishiguro N, Endo R, Kobayashi K (2003b) Latency pattern of Epstein-Barr virus and methylation status in Epstein-Barr virus-associated hemophagocytic syndrome. J Med Virol 70:410–419

    Article  PubMed  CAS  Google Scholar 

  • Youssoufian H, Hammer SM, Hirsch MS, Mulder M (1982) Methylation of the viral genome in an in vitro model of herpes simplex virus latency. Proc Natl Acad Sci USA 79:2207–2210

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Microbiological Research Group, National Center for Epidemiology, Pihenö u 1, 1529, Budapest, Hungary

    J. Minarovits

Authors
  1. J. Minarovits
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to J. Minarovits .

Editor information

Editors and Affiliations

  1. Institut für Genetik, Universität zu Köln, Zülpicher Str. 47, 50674, Köln, Germany

    Walter Doerfler  & Petra Böhm  & 

  2. Institut für Klinische und Molekulare Virologie, Universität Erlangen, Schlossgarten 4, 91054, Erlangen, Germany

    Walter Doerfler

Rights and permissions

Reprints and permissions

Copyright information

© 2006 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Minarovits, J. (2006). Epigenotypes of Latent Herpesvirus Genomes. In: Doerfler, W., Böhm, P. (eds) DNA Methylation: Development, Genetic Disease and Cancer. Current Topics in Microbiology and Immunology, vol 310. Springer, Berlin, Heidelberg . https://doi.org/10.1007/3-540-31181-5_5

Download citation

Publish with us

Policies and ethics

Search

Navigation