Abstract
Latent Epstein-Bar virus genomes undergo epigenetic modifications which are dependent on the respective tissue type and cellular phenotype. These define distinct viral epigenotypes corresponding with latent viral gene expression profiles. Viral Latent Membrane Proteins 1 and 2A can induce cellular DNA methyltransferases, thereby influencing the methylation status of the viral and cellular genomes. Therefore, not only the viral genomes carry epigenetic modifications, but also the cellular genomes adopt major epigenetic alterations upon EBV infection. The distinct cellular epigenotypes of EBV-infected cells differ from the epigenotypes of their normal counterparts. In Burkitt lymphoma (BL), nasopharyngeal carcinoma (NPC) and EBV-associated gastric carcinoma (EBVaGC) significant changes in the host cell methylome with a strong tendency towards CpG island hypermethylation are observed. Hypermethylated genes unique for EBVaGC suggest the existence of an EBV-specific “epigenetic signature”. Contrary to the primary malignancies carrying latent EBV genomes, lymphoblastoid cells (LCs) established by EBV infection of peripheral B cells in vitro are characterized by a massive genome-wide demethylation and a significant decrease and redistribution of heterochromatic histone marks. Establishing complete epigenomes of the diverse EBV-associated malignancies shall clarify their similarities and differences and further clarify the contribution of EBV to the pathogenesis, especially for the epithelial malignancies, NPC and EBVaGC.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Anastasiadou E, Boccellato F, Vincenti S, Rosato P, Bozzoni I, Frati L, Faggioni A, Presutti C, Trivedi P (2010) Epstein-Barr virus encoded LMP1 downregulates TCL1 oncogene through miR-29b. Oncogene 29:1316–1328
Anderton JA, Bose S, Vockerodt M, Vrzalikova K, Wei W, Kuo M, Helin K, Christensen J, Rowe M, Murray PG, Woodman CB (2011) The H3K27me3 demethylase, KDM6B, is induced by Epstein-Barr virus and over-expressed in Hodgkin’s lymphoma. Oncogene 30:2037–2043
Araujo I, Foss HD, Bittencourt A, Hummel M, Demel G, Mendonca N, Herbst H, Stein H (1996) Expression of Epstein-Barr virus-gene products in Burkitt’s lymphoma in Northeast Brazil. Blood 87:5279–5286
Araujo I, Foss HD, Hummel M, Anagnostopoulos I, Barbosa HS, Bittencourt A, Stein H (1999) Frequent expansion of Epstein-Barr virus (EBV) infected cells in germinal centres of tonsils from an area with a high incidence of EBV-associated lymphoma. J Pathol 187:326–330
Arvey A, Tempera I, Tsai K, Chen HS, Tikhmyanova N, Klichinsky M, Leslie C, Lieberman PM (2012) An atlas of the Epstein-Barr virus transcriptome and epigenome reveals host-virus regulatory interactions. Cell Host Microbe 12:233–245
Arvey A, Tempera I, Lieberman PM (2013) Interpreting the Epstein-Barr Virus (EBV) epigenome using high-throughput data. Viruses 5:1042–1054
Au WY, Pang A, Chan EC, Chu KM, Shek TW, Kwong YL (2005) Epstein-barr virus-related gastric adenocarcinoma: an early secondary cancer post hemopoietic stem cell transplantation. Gastroenterology 129:2058–2063
Ayadi W, Karray-Hakim H, Khabir A, Feki L, Charfi S, Boudawara T, Ghorbel A, Daoud J, Frikha M, Busson P, Hammami A (2008) Aberrant methylation of p16, DLEC1, BLU and E-cadherin gene promoters in nasopharyngeal carcinoma biopsies from Tunisian patients. Anticancer Res 28:2161–2167
Babcock GJ, Decker LL, Volk M, Thorley-Lawson DA (1998) EBV persistence in memory B cells in vivo. Immunity 9:395–404
Baer R, Bankier AT, Biggin MD, Deininger PL, Farrell PJ, Gibson TJ, Hatfull G, Hudson GS, Satchwell SC, Seguin C (1984) DNA sequence and expression of the B95-8 Epstein-Barr virus genome. Nature 310:207–211
Bailey SD, Zhang X, Desai K, Aid M, Corradin O, Cowper-Sal Lari R, Akhtar-Zaidi B, Scacheri PC, Haibe-Kains B, Lupien M (2015) ZNF143 provides sequence specificity to secure chromatin interactions at gene promoters. Nat Commun 2:6186
Banati F, Koroknai A, Salamon D, Takacs M, Minarovits-Kormuta S, Wolf H, Niller HH, Minarovits J (2008) CpG-methylation silences the activity of the RNA polymerase III transcribed EBER-1 promoter of Epstein-Barr virus. FEBS Lett 582:705–709
Barth S, Pfuhl T, Mamiani A, Ehses C, Roemer K, Kremmer E, Jaker C, Hock J, Meister G, Grasser FA (2008) Epstein-Barr virus-encoded microRNA miR-BART2 down-regulates the viral DNA polymerase BALF5. Nucleic Acids Res 36:666–675
Baylin SB, Jones PA (2011) A decade of exploring the cancer epigenome – biological and translational implications. Nat Rev Cancer 11:726–734
Boccellato F, Anastasiadou E, Rosato P, Kempkes B, Frati L, Faggioni A, Trivedi P (2007) EBNA2 interferes with the germinal center phenotype by downregulating BCL6 and TCL1 in non-Hodgkin’s lymphoma cells. J Virol 81:2274–2282
Borza CM, Hutt-Fletcher LM (2002) Alternate replication in B cells and epithelial cells switches tropism of Epstein-Barr virus. Nat Med 8:594–599
Brink AA, Dukers DF, van den Brule AJ, Oudejans JJ, Middeldorp JM, Meijer CJ, Jiwa M (1997) Presence of Epstein-Barr virus latency type III at the single cell level in post-transplantation lymphoproliferative disorders and AIDS related lymphomas. J Clin Pathol 50:911–918
Burke AP, Yen TS, Shekitka KM, Sobin LH (1990) Lymphoepithelial carcinoma of the stomach with Epstein-Barr virus demonstrated by polymerase chain reaction. Mod Pathol 3:377–380
Cai X, Schafer A, Lu S, Bilello JP, Desrosiers RC, Edwards R, Raab-Traub N, Cullen BR (2006) Epstein-Barr virus microRNAs are evolutionarily conserved and differentially expressed. PLoS Pathog 2:e23
Cai MY, Tong ZT, Zhu W, Wen ZZ, Rao HL, Kong LL, Guan XY, Kung HF, Zeng YX, Xie D (2011) H3K27me3 protein is a promising predictive biomarker of patients’ survival and chemoradioresistance in human nasopharyngeal carcinoma. Mol Med 17:1137–1145
Caliskan M, Cusanovich DA, Ober C, Gilad Y (2011) The effects of EBV transformation on gene expression levels and methylation profiles. Hum Mol Genet 20:1643–1652
Canaan A, Haviv I, Urban AE, Schulz VP, Hartman S, Zhang Z, Palejev D, Deisseroth AB, Lacy J, Snyder M, Gerstein M, Weissman SM (2009) EBNA1 regulates cellular gene expression by binding cellular promoters. Proc Natl Acad Sci U S A 106:22421–22426
Cancer Genome Atlas Research Network (2014) Comprehensive molecular characterization of gastric adenocarcinoma. Nature 513:202–209
Challouf S, Ziadi S, Zaghdoudi R, Ksiaa F, Ben Gacem R, Trimeche M (2012) Patterns of aberrant DNA hypermethylation in nasopharyngeal carcinoma in Tunisian patients. Clin Chim Acta 413:795–802
Chang MS, Lee HS, Kim HS, Kim SH, Choi SI, Lee BL, Kim CW, Kim YI, Yang M, Kim WH (2003) Epstein-Barr virus and microsatellite instability in gastric carcinogenesis. J Pathol 199:447–452
Chau CM, Zhang XY, McMahon SB, Lieberman PM (2006) Regulation of Epstein-Barr virus latency type by the chromatin boundary factor CTCF. J Virol 80:5723–5732
Cheng Y, Geng H, Cheng SH, Liang P, Bai Y, Li J, Srivastava G, Ng MH, Fukagawa T, Wu X, Chan AT, Tao Q (2010) KRAB zinc finger protein ZNF382 is a proapoptotic tumor suppressor that represses multiple oncogenes and is commonly silenced in multiple carcinomas. Cancer Res 70:6516–6526
Cheung HW, Ching YP, Nicholls JM, Ling MT, Wong YC, Hui N, Cheung A, Tsao SW, Wang Q, Yeun PW, Lo KW, Jin DY, Wang X (2005) Epigenetic inactivation of CHFR in nasopharyngeal carcinoma through promoter methylation. Mol Carcinog 43:237–245
Chong JM, Sakuma K, Sudo M, Ushiku T, Uozaki H, Shibahara J, Nagai H, Funata N, Taniguchi H, Aburatani H, Fukayama M (2003) Global and non-random CpG-island methylation in gastric carcinoma associated with Epstein-Barr virus. Cancer Sci 94:76–80
Choy EY, Siu KL, Kok KH, Lung RW, Tsang CM, To KF, Kwong DL, Tsao SW, Jin DY (2008) An Epstein-Barr virus-encoded microRNA targets PUMA to promote host cell survival. J Exp Med 205:2551–2560
Clarke PA, Schwemmle M, Schickinger J, Hilse K, Clemens MJ (1991) Binding of Epstein-Barr virus small RNA EBER-1 to the double-stranded RNA-activated protein kinase DAI. Nucleic Acids Res 19:243–248
Coffey AJ, Brooksbank RA, Brandau O, Oohashi T, Howell GR, Bye JM, Cahn AP, Durham J, Heath P, Wray P, Pavitt R, Wilkinson J, Leversha M, Huckle E, Shaw-Smith CJ, Dunham A, Rhodes S, Schuster V, Porta G, Yin L, Serafini P, Sylla B, Zollo M, Franco B, Bolino A, Seri M, Lanyi A, Davis JR, Webster D, Harris A, Lenoir G, de St Basile G, Jones A, Behloradsky BH, Achatz H, Murken J, Fassler R, Sumegi J, Romeo G, Vaudin M, Ross MT, Meindl A, Bentley DR (1998) Host response to EBV infection in X-linked lymphoproliferative disease results from mutations in an SH2-domain encoding gene. Nat Genet 20:129–135
Coppotelli G, Mughal N, Callegari S, Sompallae R, Caja L, Luijsterburg MS, Dantuma NP, Moustakas A, Masucci MG (2013) The Epstein-Barr virus nuclear antigen-1 reprograms transcription by mimicry of high mobility group A proteins. Nucleic Acids Res 41:2950–2962
Costello JF, Fruhwald MC, Smiraglia DJ, Rush LJ, Robertson GP, Gao X, Wright FA, Feramisco JD, Peltomaki P, Lang JC, Schuller DE, Yu L, Bloomfield CD, Caligiuri MA, Yates A, Nishikawa R, Su Huang H, Petrelli NJ, Zhang X, O’Dorisio MS, Held WA, Cavenee WK, Plass C (2000) Aberrant CpG-island methylation has non-random and tumour-type-specific patterns. Nat Genet 24:132–138
Cotter MA, Robertson ES (2000) Modulation of histone acetyltransferase activity through interaction of Epstein-Barr nuclear antigen 3C with prothymosin alpha. Mol Cell Biol 20:5722–5735
Cui Y, Ying Y, van Hasselt A, Ng KM, Yu J, Zhang Q, Jin J, Liu D, Rhim JS, Rha SY, Loyo M, Chan AT, Srivastava G, Tsao GS, Sellar GC, Sung JJ, Sidransky D, Tao Q (2008) OPCML is a broad tumor suppressor for multiple carcinomas and lymphomas with frequently epigenetic inactivation. PLoS One 3:e2990
Cui Y, Gao D, Linghu E, Zhan Q, Chen R, Brock MV, Herman JG, Guo M (2015) Epigenetic changes and functional study of HOXA11 in human gastric cancer. Epigenomics 7:201–213
Dai W, Cheung AK, Ko JM, Cheng Y, Zheng H, Ngan RK, Ng WT, Lee AW, Yau CC, Lee VH, Lung ML (2015) Comparative methylome analysis in solid tumors reveals aberrant methylation at chromosome 6p in nasopharyngeal carcinoma. Cancer Med 4:1079–1090
de The G (1984) Virus-associated lymphomas, leukaemias and immunodeficiencies in Africa. IARC Sci Publ 63:727–744
de The G (1985) The Epstein-Barr virus (EBV): a Rosetta Stone for understanding the role of viruses in immunopathological disorders and in human carcinogenesis. Biomed Pharmacother 39:49–51
Decaussin G, Sbih-Lammali F, de Turenne-Tessier M, Bouguermouh A, Ooka T (2000) Expression of BARF1 gene encoded by Epstein-Barr virus in nasopharyngeal carcinoma biopsies. Cancer Res 60:5584–5588
Degner SC, Wong TP, Jankevicius G, Feeney AJ (2009) Cutting edge: developmental stage-specific recruitment of cohesin to CTCF sites throughout immunoglobulin loci during B lymphocyte development. J Immunol 182:44–48
d’Herouel AF, Birgersdotter A, Werner M (2010) FR-like EBNA1 binding repeats in the human genome. Virology 405:524–529
Dolken L, Malterer G, Erhard F, Kothe S, Friedel CC, Suffert G, Marcinowski L, Motsch N, Barth S, Beitzinger M, Lieber D, Bailer SM, Hoffmann R, Ruzsics Z, Kremmer E, Pfeffer S, Zimmer R, Koszinowski UH, Grasser F, Meister G, Haas J (2010) Systematic analysis of viral and cellular microRNA targets in cells latently infected with human gamma-herpesviruses by RISC immunoprecipitation assay. Cell Host Microbe 7:324–334
Dresang LR, Vereide DT, Sugden B (2009) Identifying sites bound by Epstein-Barr virus nuclear antigen 1 (EBNA1) in the human genome: defining a position-weighted matrix to predict sites bound by EBNA1 in viral genomes. J Virol 83:2930–2940
Du ZM, Hu LF, Wang HY, Yan LX, Zeng YX, Shao JY, Ernberg I (2011) Upregulation of MiR-155 in nasopharyngeal carcinoma is partly driven by LMP1 and LMP2A and downregulates a negative prognostic marker JMJD1A. PLoS One 6:e19137
Durst M, Gissmann L, Ikenberg H, zur Hausen H (1983) A papillomavirus DNA from a cervical carcinoma and its prevalence in cancer biopsy samples from different geographic regions. Proc Natl Acad Sci U S A 80:3812–3815
Dutton A, Woodman CB, Chukwuma MB, Last JI, Wei W, Vockerodt M, Baumforth KR, Flavell JR, Rowe M, Taylor AM, Young LS, Murray PG (2007) Bmi-1 is induced by the Epstein-Barr virus oncogene LMP1 and regulates the expression of viral target genes in Hodgkin lymphoma cells. Blood 109:2597–2603
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 78:14062–14065
Enomoto S, Maekita T, Tsukamoto T, Nakajima T, Nakazawa K, Tatematsu M, Ichinose M, Ushijima T (2007) Lack of association between CpG island methylator phenotype in human gastric cancers and methylation in their background non-cancerous gastric mucosae. Cancer Sci 98:1853–1861
Epstein MA, Achong BG, Barr YM (1964) Virus particles in cultured lymphoblasts from Burkitt’s lymphoma. Lancet 1:702–703
Esteller M (2007a) Cancer epigenomics: DNA methylomes and histone-modification maps. Nat Rev Genet 8:286–298
Esteller M (2007b) Epigenetic gene silencing in cancer: the DNA hypermethylome. Hum Mol Genet 16(Spec No 1):R50–R59
Evans AS, Rothfield NF, Niederman JC (1971) Raised antibody titres to E.B. virus in systemic lupus erythematosus. Lancet 1:167–168
Fejer G, Koroknai A, Banati F, Gyory I, Salamon D, Wolf H, Niller HH, Minarovits J (2008) Latency type-specific distribution of epigenetic marks at the alternative promoters Cp and Qp of Epstein-Barr virus. J Gen Virol 89:1364–1370
Fernandez AF, Rosales C, Lopez-Nieva P, Grana O, Ballestar E, Ropero S, Espada J, Melo SA, Lujambio A, Fraga MF, Pino I, Javierre B, Carmona FJ, Acquadro F, Steenbergen RD, Snijders PJ, Meijer CJ, Pineau P, Dejean A, Lloveras B, Capella G, Quer J, Buti M, Esteban JI, Allende H, Rodriguez-Frias F, Castellsague X, Minarovits J, Ponce J, Capello D, Gaidano G, Cigudosa JC, Gomez-Lopez G, Pisano DG, Valencia A, Piris MA, Bosch FX, Cahir-McFarland E, Kieff E, Esteller M (2009) The dynamic DNA methylomes of double-stranded DNA viruses associated with human cancer. Genome Res 19:438–451
Fingeroth JD, Weis JJ, Tedder TF, Strominger JL, Biro PA, Fearon DT (1984) Epstein-Barr virus receptor of human B lymphocytes is the C3d receptor CR2. Proc Natl Acad Sci U S A 81:4510–4514
Finke J, Rowe M, Kallin B, Ernberg I, Rosen A, Dillner J, Klein G (1987) Monoclonal and polyclonal antibodies against Epstein-Barr virus nuclear antigen 5 (EBNA-5) detect multiple protein species in Burkitt’s lymphoma and lymphoblastoid cell lines. J Virol 61:3870–3878
Fuentes-Panana EM, Peng R, Brewer G, Tan J, Ling PD (2000) Regulation of the Epstein-Barr virus C promoter by AUF1 and the cyclic AMP/protein kinase A signaling pathway. J Virol 74:8166–8175
Fukuda M, Longnecker R (2007) Epstein-Barr virus latent membrane protein 2A mediates transformation through constitutive activation of the Ras/PI3-K/Akt Pathway. J Virol 81:9299–9306
Gahn TA, Sugden B (1995) 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 69:2633–2636
Gerle B, Koroknai A, Fejer G, Bakos A, Banati F, Szenthe K, Wolf H, Niller HH, Minarovits J, Salamon D (2007) Acetylated histone H3 and H4 mark the upregulated LMP2A promoter of Epstein-Barr virus in lymphoid cells. J Virol 81:13242–13247
Guelen L, Pagie L, Brasset E, Meuleman W, Faza MB, Talhout W, Eussen BH, de Klein A, Wessels L, de Laat W, van Steensel B (2008) Domain organization of human chromosomes revealed by mapping of nuclear lamina interactions. Nature 453:948–951
Gyory I, Minarovits J (2005) Epigenetic regulation of lymphoid specific gene sets. Biochem Cell Biol 83:286–295
Hadinoto V, Shapiro M, Sun CC, Thorley-Lawson DA (2009) The dynamics of EBV shedding implicate a central role for epithelial cells in amplifying viral output. PLoS Pathog 5:e1000496
Hamilton-Dutoit SJ, Raphael M, Audouin J, Diebold J, Lisse I, Pedersen C, Oksenhendler E, Marelle L, Pallesen G (1993) In situ demonstration of Epstein-Barr virus small RNAs (EBER 1) in acquired immunodeficiency syndrome-related lymphomas: correlation with tumor morphology and primary site. Blood 82:619–624
Hammerschmidt W, Sugden B (1989) Genetic analysis of immortalizing functions of Epstein-Barr virus in human B lymphocytes. Nature 340:393–397
Hansen KD, Timp W, Bravo HC, Sabunciyan S, Langmead B, McDonald OG, Wen B, Wu H, Liu Y, Diep D, Briem E, Zhang K, Irizarry RA, Feinberg AP (2011) Increased methylation variation in epigenetic domains across cancer types. Nat Genet 43:768–775
Hansen KD, Sabunciyan S, Langmead B, Nagy N, Curley R, Klein G, Klein E, Salamon D, Feinberg AP (2014) Large-scale hypomethylated blocks associated with Epstein-Barr virus-induced B-cell immortalization. Genome Res 24:177–184
Harabuchi Y, Yamanaka N, Kataura A, Imai S, Kinoshita T, Mizuno F, Osato T (1990) Epstein-Barr virus in nasal T-cell lymphomas in patients with lethal midline granuloma. Lancet 335:128–130
Hawkins JB, Delgado-Eckert E, Thorley-Lawson DA, Shapiro M (2013) The cycle of EBV infection explains persistence, the sizes of the infected cell populations and which come under CTL regulation. PLoS Pathog 9:e1003685
He D, Zeng Q, Ren G, Xiang T, Qian Y, Hu Q, Zhu J, Hong S, Hu G (2012) Protocadherin8 is a functional tumor suppressor frequently inactivated by promoter methylation in nasopharyngeal carcinoma. Eur J Cancer Prev 21:569–575
He D, Zhang YW, Zhang NN, Zhou L, Chen JN, Jiang Y, Shao CK (2015) Aberrant gene promoter methylation of p16, FHIT, CRBP1, WWOX, and DLC-1 in Epstein-Barr virus-associated gastric carcinomas. Med Oncol 32:525
Henle G, Henle W (1966) Immunofluorescence in cells derived from Burkitt’s lymphoma. J Bacteriol 91:1248–1256
Henle W, Diehl V, Kohn G, Zur Hausen H, Henle G (1967) Herpes-type virus and chromosome marker in normal leukocytes after growth with irradiated Burkitt cells. Science 157:1064–1065
Henle G, Henle W, Diehl V (1968) Relation of Burkitt’s tumor-associated herpes-type virus to infectious mononucleosis. Proc Natl Acad Sci U S A 59:94–101
Hernando H, Shannon-Lowe C, Islam AB, Al-Shahrour F, Rodriguez-Ubreva J, Rodriguez-Cortez VC, Javierre BM, Mangas C, Fernandez AF, Parra M, Delecluse HJ, Esteller M, Lopez-Granados E, Fraga MF, Lopez-Bigas N, Ballestar E (2013) The B cell transcription program mediates hypomethylation and overexpression of key genes in Epstein-Barr virus-associated proliferative conversion. Genome Biol 14:R3
Hernando H, Islam AB, Rodriguez-Ubreva J, Forne I, Ciudad L, Imhof A, Shannon-Lowe C, Ballestar E (2014) Epstein-Barr virus-mediated transformation of B cells induces global chromatin changes independent to the acquisition of proliferation. Nucleic Acids Res 42:249–263
Hino R, Uozaki H, Murakami N, Ushiku T, Shinozaki A, Ishikawa S, Morikawa T, Nakaya T, Sakatani T, Takada K, Fukayama M (2009) Activation of DNA methyltransferase 1 by EBV latent membrane protein 2A leads to promoter hypermethylation of PTEN gene in gastric carcinoma. Cancer Res 69:2766–2774
Hochberg D, Souza T, Catalina M, Sullivan JL, Luzuriaga K, Thorley-Lawson DA (2004) Acute infection with Epstein-Barr virus targets and overwhelms the peripheral memory B-cell compartment with resting, latently infected cells. J Virol 78:5194–5204
Holdorf MM, Cooper SB, Yamamoto KR, Miranda JJ (2011) Occupancy of chromatin organizers in the Epstein-Barr virus genome. Virology 415:1–5
Horikawa T, Yang J, Kondo S, Yoshizaki T, Joab I, Furukawa M, Pagano JS (2007) Twist and epithelial-mesenchymal transition are induced by the EBV oncoprotein latent membrane protein 1 and are associated with metastatic nasopharyngeal carcinoma. Cancer Res 67:1970–1978
Hsu CY, Yi YH, Chang KP, Chang YS, Chen SJ, Chen HC (2014) The Epstein-Barr virus-encoded microRNA MiR-BART9 promotes tumor metastasis by targeting E-cadherin in nasopharyngeal carcinoma. PLoS Pathog 10:e1003974
Hughes DJ, Dickerson CA, Shaner MS, Sample CE, Sample JT (2011) trans-Repression of protein expression dependent on the Epstein-Barr virus promoter Wp during latency. J Virol 85:11435–11447
Hughes DJ, Marendy EM, Dickerson CA, Yetming KD, Sample CE, Sample JT (2012) Contributions of CTCF and DNA methyltransferases DNMT1 and DNMT3B to Epstein-Barr virus restricted latency. J Virol 86:1034–1045
Hui AB, Lo KW, Kwong J, Lam EC, Chan SY, Chow LS, Chan AS, Teo PM, Huang DP (2003) Epigenetic inactivation of TSLC1 gene in nasopharyngeal carcinoma. Mol Carcinog 38:170–178
Hurley EA, Thorley-Lawson DA (1988) B cell activation and the establishment of Epstein-Barr virus latency. J Exp Med 168:2059–2075
Hurley EA, Agger S, McNeil JA, Lawrence JB, Calendar A, Lenoir G, Thorley-Lawson DA (1991) When Epstein-Barr virus persistently infects B-cell lines, it frequently integrates. J Virol 65:1245–1254
Hutajulu SH, Indrasari SR, Indrawati LP, Harijadi A, Duin S, Haryana SM, Steenbergen RD, Greijer AE, Middeldorp JM (2011) Epigenetic markers for early detection of nasopharyngeal carcinoma in a high risk population. Mol Cancer 10:48
Hwang CF, Huang HY, Chen CH, Chien CY, Hsu YC, Li CF, Fang FM (2012) Enhancer of zeste homolog 2 overexpression in nasopharyngeal carcinoma: an independent poor prognosticator that enhances cell growth. Int J Radiat Oncol Biol Phys 82:597–604
Iwakiri D, Zhou L, Samanta M, Matsumoto M, Ebihara T, Seya T, Imai S, Fujieda M, Kawa K, Takada K (2009) Epstein-Barr virus (EBV)-encoded small RNA is released from EBV-infected cells and activates signaling from Toll-like receptor 3. J Exp Med 206:2091–2099
Jankelevich S, Kolman JL, Bodnar JW, Miller G (1992) A nuclear matrix attachment region organizes the Epstein-Barr viral plasmid in Raji cells into a single DNA domain. EMBO J 11:1165–1176
Jansson A, Masucci M, Rymo L (1992) Methylation of discrete sites within the enhancer region regulates the activity of the Epstein-Barr virus BamHI W promoter in Burkitt lymphoma lines. J Virol 66:62–69
Jin H, Wang X, Ying J, Wong AH, Cui Y, Srivastava G, Shen ZY, Li EM, Zhang Q, Jin J, Kupzig S, Chan AT, Cullen PJ, Tao Q (2007a) Epigenetic silencing of a Ca(2+)-regulated Ras GTPase-activating protein RASAL defines a new mechanism of Ras activation in human cancers. Proc Natl Acad Sci U S A 104:12353–12358
Jin H, Wang X, Ying J, Wong AH, Li H, Lee KY, Srivastava G, Chan AT, Yeo W, Ma BB, Putti TC, Lung ML, Shen ZY, Xu LY, Langford C, Tao Q (2007b) Epigenetic identification of ADAMTS18 as a novel 16q23.1 tumor suppressor frequently silenced in esophageal, nasopharyngeal and multiple other carcinomas. Oncogene 26:7490–7498
Johannsen E, Koh E, Mosialos G, Tong X, Kieff E, Grossman SR (1995) Epstein-Barr virus nuclear protein 2 transactivation of the latent membrane protein 1 promoter is mediated by J kappa and PU.1. J Virol 69:253–262
Johannsen E, Miller CL, Grossman SR, Kieff E (1996) EBNA-2 and EBNA-3C extensively and mutually exclusively associate with RBPJkappa in Epstein-Barr virus-transformed B lymphocytes. J Virol 70:4179–4183
Jourdan N, Jobart-Malfait A, Dos Reis G, Quignon F, Piolot T, Klein C, Tramier M, Coppey-Moisan M, Marechal V (2012) Live-cell imaging reveals multiple interactions between Epstein-Barr virus nuclear antigen 1 and cellular chromatin during interphase and mitosis. J Virol 86:5314–5329
Jung YJ, Choi H, Kim H, Lee SK (2014) MicroRNA miR-BART20-5p stabilizes Epstein-Barr virus latency by directly targeting BZLF1 and BRLF1. J Virol 88:9027–9037
Kalla M, Hammerschmidt W (2012) Human B cells on their route to latent infection – early but transient expression of lytic genes of Epstein-Barr virus. Eur J Cell Biol 91:65–69
Kalter SP, Riggs SA, Cabanillas F, Butler JJ, Hagemeister FB, Mansell PW, Newell GR, Velasquez WS, Salvador P, Barlogie B, Rios A, Hersh EM (1985) Aggressive Non-Hodgkin’s lymphomas in immunocompromised homosexual males. Blood 66:655–659
Kanda T, Miyata M, Kano M, Kondo S, Yoshizaki T, Iizasa H (2015) Clustered microRNAs of the Epstein-Barr virus cooperatively downregulate an epithelial cell-specific metastasis suppressor. J Virol 89:2684–2697
Kaneda A, Matsusaka K, Aburatani H, Fukayama M (2012) Epstein-Barr virus infection as an epigenetic driver of tumorigenesis. Cancer Res 72:3445–3450
Kang GH, Lee S, Kim WH, Lee HW, Kim JC, Rhyu MG, Ro JY (2002) Epstein-Barr virus-positive gastric carcinoma demonstrates frequent aberrant methylation of multiple genes and constitutes CpG island methylator phenotype-positive gastric carcinoma. Am J Pathol 160:787–794
Kang GH, Lee S, Cho NY, Gandamihardja T, Long TI, Weisenberger DJ, Campan M, Laird PW (2008) DNA methylation profiles of gastric carcinoma characterized by quantitative DNA methylation analysis. Lab Invest 88:161–170
Kang H, Wiedmer A, Yuan Y, Robertson E, Lieberman PM (2011) Coordination of KSHV latent and lytic gene control by CTCF-cohesin mediated chromosome conformation. PLoS Pathog 7:e1002140
Kelly G, Bell A, Rickinson A (2002) Epstein-Barr virus-associated Burkitt lymphomagenesis selects for downregulation of the nuclear antigen EBNA2. Nat Med 8:1098–1104
Kelly GL, Milner AE, Baldwin GS, Bell AI, Rickinson AB (2006) Three restricted forms of Epstein-Barr virus latency counteracting apoptosis in c-myc-expressing Burkitt lymphoma cells. Proc Natl Acad Sci U S A 103:14935–14940
Kim DN, Chae HS, Oh ST, Kang JH, Park CH, Park WS, Takada K, Lee JM, Lee WK, Lee SK (2007) Expression of viral microRNAs in Epstein-Barr virus-associated gastric carcinoma. J Virol 81:1033–1036
Kis LL, Salamon D, Persson EK, Nagy N, Scheeren FA, Spits H, Klein G, Klein E (2010) IL-21 imposes a type II EBV gene expression on type III and type I B cells by the repression of C- and activation of LMP-1-promoter. Proc Natl Acad Sci U S A 107:872–877
Klein G (1987) In defense of the “old” Burkitt lymphoma scenario. In: Klein G (ed) Advances in viral oncology. Raven Press, New York, pp 207–211
Klein E, Nagy N (2010) Restricted expression of EBV encoded proteins in in vitro infected CLL cells. Semin Cancer Biol 20:410–415
Klein E, Nagy N, Rasul AE (2013) EBV genome carrying B lymphocytes that express the nuclear protein EBNA-2 but not LMP-1: type IIb latency. Oncoimmunology 2:e23035
Knight JS, Lan K, Subramanian C, Robertson ES (2003) Epstein-Barr virus nuclear antigen 3C recruits histone deacetylase activity and associates with the corepressors mSin3A and NCoR in human B-cell lines. J Virol 77:4261–4272
Kong QL, Hu LJ, Cao JY, Huang YJ, Xu LH, Liang Y, Xiong D, Guan S, Guo BH, Mai HQ, Chen QY, Zhang X, Li MZ, Shao JY, Qian CN, Xia YF, Song LB, Zeng YX, Zeng MS (2010) Epstein-Barr virus-encoded LMP2A induces an epithelial-mesenchymal transition and increases the number of side population stem-like cancer cells in nasopharyngeal carcinoma. PLoS Pathog 6:e1000940
Kreck B, Richter J, Ammerpohl O, Barann M, Esser D, Petersen BS, Vater I, Murga Penas EM, Bormann Chung CA, Seisenberger S, Lee Boyd V, Smallwood S, Drexler HG, Macleod RA, Hummel M, Krueger F, Hasler R, Schreiber S, Rosenstiel P, Franke A, Siebert R (2013) Base-pair resolution DNA methylome of the EBV-positive Endemic Burkitt lymphoma cell line DAUDI determined by SOLiD bisulfite-sequencing. Leukemia 27:1751–1753
Kurth J, Spieker T, Wustrow J, Strickler GJ, Hansmann LM, Rajewsky K, Kuppers R (2000) EBV-infected B cells in infectious mononucleosis: viral strategies for spreading in the B cell compartment and establishing latency. Immunity 13:485–495
Kurth J, Hansmann ML, Rajewsky K, Kuppers R (2003) Epstein-Barr virus-infected B cells expanding in germinal centers of infectious mononucleosis patients do not participate in the germinal center reaction. Proc Natl Acad Sci U S A 100:4730–4735
Kwong J, Lo KW, To KF, Teo PM, Johnson PJ, Huang DP (2002) Promoter hypermethylation of multiple genes in nasopharyngeal carcinoma. Clin Cancer Res 8:131–137
Kwong J, Lo KW, Chow LS, Chan FL, To KF, Huang DP (2005a) Silencing of the retinoid response gene TIG1 by promoter hypermethylation in nasopharyngeal carcinoma. Int J Cancer 113:386–392
Kwong J, Lo KW, Chow LS, To KF, Choy KW, Chan FL, Mok SC, Huang DP (2005b) Epigenetic silencing of cellular retinol-binding proteins in nasopharyngeal carcinoma. Neoplasia 7:67–74
Lan J, Tai HC, Lee SW, Chen TJ, Huang HY, Li CF (2014) Deficiency in expression and epigenetic DNA Methylation of ASS1 gene in nasopharyngeal carcinoma: negative prognostic impact and therapeutic relevance. Tumour Biol 35:161–169
Latour S, Veillette A (2003) Molecular and immunological basis of X-linked lymphoproliferative disease. Immunol Rev 192:212–224
Laux G, Perricaudet M, Farrell PJ (1988) A spliced Epstein-Barr virus gene expressed in immortalized lymphocytes is created by circularization of the linear viral genome. EMBO J 7:769–774
Lee KY, Geng H, Ng KM, Yu J, van Hasselt A, Cao Y, Zeng YX, Wong AH, Wang X, Ying J, Srivastava G, Lung ML, Wang LD, Kwok TT, Levi BZ, Chan AT, Sung JJ, Tao Q (2008) Epigenetic disruption of interferon-gamma response through silencing the tumor suppressor interferon regulatory factor 8 in nasopharyngeal, esophageal and multiple other carcinomas. Oncogene 27:5267–5276
Lei T, Yuen KS, Xu R, Tsao SW, Chen H, Li M, Kok KH, Jin DY (2013) Targeting of DICE1 tumor suppressor by Epstein-Barr virus-encoded miR-BART3* microRNA in nasopharyngeal carcinoma. Int J Cancer 133:79–87
Lenoir GM, Bornkamm G (1987) Burkitt’s Lymphoma, a human cancer model for the study of the multistep development of cancer: proposal for a new scenario. In: Klein G (ed) Advances in viral oncology. Raven Press, New York, pp 173–206
Leonard S, Wei W, Anderton J, Vockerodt M, Rowe M, Murray PG, Woodman CB (2011) Epigenetic and transcriptional changes which follow Epstein-Barr virus infection of germinal center B cells and their relevance to the pathogenesis of Hodgkin’s lymphoma. J Virol 85:9568–9577
Lewin N, Minarovits J, Weber G, Ehlin-Henriksson B, Wen T, Mellstedt H, Klein G, Klein E (1991) Clonality and methylation status of the Epstein-Barr virus (EBV) genomes in in vivo-infected EBV-carrying chronic lymphocytic leukemia (CLL) cell lines. Int J Cancer 48:62–66
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
Li G, Wu Z, Peng Y, Liu X, Lu J, Wang L, Pan Q, He ML, Li XP (2010) MicroRNA-10b induced by Epstein-Barr virus-encoded latent membrane protein-1 promotes the metastasis of human nasopharyngeal carcinoma cells. Cancer Lett 299:29–36
Li LL, Shu XS, Wang ZH, Cao Y, Tao Q (2011) Epigenetic disruption of cell signaling in nasopharyngeal carcinoma. Chin J Cancer 30:231–239
Li L, Zhang Y, Fan Y, Sun K, Su X, Du Z, Tsao SW, Loh TK, Sun H, Chan AT, Zeng YX, Chan WY, Chan FK, Tao Q (2014a) Characterization of the nasopharyngeal carcinoma methylome identifies aberrant disruption of key signaling pathways and methylated tumor suppressor genes. Epigenomics 7:155–173
Li L, Zhang Y, Guo BB, Chan FK, Tao Q (2014b) Oncogenic induction of cellular high CpG methylation by Epstein-Barr virus in malignant epithelial cells. Chin J Cancer 33:604–608
Lin IG, Tomzynski TJ, Ou Q, Hsieh CL (2000) Modulation of DNA binding protein affinity directly affects target site demethylation. Mol Cell Biol 20:2343–2349
Lin A, Wang S, Nguyen T, Shire K, Frappier L (2008) The EBNA1 protein of Epstein-Barr virus functionally interacts with Brd4. J Virol 82:12009–12019
Ling PD, Rawlins DR, Hayward SD (1993) The Epstein-Barr virus immortalizing protein EBNA-2 is targeted to DNA by a cellular enhancer-binding protein. Proc Natl Acad Sci U S A 90:9237–9241
Ling PD, Peng RS, Nakajima A, Yu JH, Tan J, Moses SM, Yang WH, Zhao B, Kieff E, Bloch KD, Bloch DB (2005) Mediation of Epstein-Barr virus EBNA-LP transcriptional coactivation by Sp100. EMBO J 24:3565–3575
Liu H, Zhang L, Niu Z, Zhou M, Peng C, Li X, Deng T, Shi L, Tan Y, Li G (2008) Promoter methylation inhibits BRD7 expression in human nasopharyngeal carcinoma cells. BMC Cancer 8:253
Liu X, Wang Y, Wang X, Sun Z, Li L, Tao Q, Luo B (2013) Epigenetic silencing of WNT5A in Epstein-Barr virus-associated gastric carcinoma. Arch Virol 158:123–132
Lo KW, Cheung ST, Leung SF, van Hasselt A, Tsang YS, Mak KF, Chung YF, Woo JK, Lee JC, Huang DP (1996) Hypermethylation of the p16 gene in nasopharyngeal carcinoma. Cancer Res 56:2721–2725
Lo KW, Kwong J, Hui AB, Chan SY, To KF, Chan AS, Chow LS, Teo PM, Johnson PJ, Huang DP (2001) High frequency of promoter hypermethylation of RASSF1A in nasopharyngeal carcinoma. Cancer Res 61:3877–3881
Lo KW, Tsang YS, Kwong J, To KF, Teo PM, Huang DP (2002) Promoter hypermethylation of the EDNRB gene in nasopharyngeal carcinoma. Int J Cancer 98:651–655
Lo AK, To KF, Lo KW, Lung RW, Hui JW, Liao G, Hayward SD (2007) Modulation of LMP1 protein expression by EBV-encoded microRNAs. Proc Natl Acad Sci U S A 104:16164–16169
Lo KW, Chung GT, To KF (2012) Deciphering the molecular genetic basis of NPC through molecular, cytogenetic, and epigenetic approaches. Semin Cancer Biol 22:79–86
Lo KW, Chung GT, To K (2013) Acquired genetic and epigenetic alterations in nasopharyngeal carcinoma. In: Busson P (ed) Nasopharyngeal carcinoma. Springer, New York, pp 61–81
Longnecker R, Kieff E, Cohen JI (2013) Epstein Barr virus. In: Knipe DM, Howley PM (eds) Fields virology, 6th edn. Lippincott Williams & Wilkins, Philadelphia, pp 1898–1959
Lu F, Wikramasinghe P, Norseen J, Tsai K, Wang P, Showe L, Davuluri RV, Lieberman PM (2010) Genome-wide analysis of host-chromosome binding sites for Epstein-Barr Virus Nuclear Antigen 1 (EBNA1). Virol J 7:262
Lu J, Murakami M, Verma SC, Cai Q, Haldar S, Kaul R, Wasik MA, Middeldorp J, Robertson ES (2011) Epstein-Barr Virus nuclear antigen 1 (EBNA1) confers resistance to apoptosis in EBV-positive B-lymphoma cells through up-regulation of survivin. Virology 410:64–75
Lu F, Tempera I, Lee HT, Dewispelaere K, Lieberman PM (2014) EBNA1 binding and epigenetic regulation of gastrokine tumor suppressor genes in gastric carcinoma cells. Virol J 11:12
Lubega J (2007) T-helper 1 versus T-helper 2 lymphocyte immunodysregulation is the central factor in genesis of Burkitt lymphoma: hypothesis. Infect Agent Cancer 2:10
Lung HL, Lo PH, Xie D, Apte SS, Cheung AK, Cheng Y, Law EW, Chua D, Zeng YX, Tsao SW, Stanbridge EJ, Lung ML (2008) Characterization of a novel epigenetically-silenced, growth-suppressive gene, ADAMTS9, and its association with lymph node metastases in nasopharyngeal carcinoma. Int J Cancer 123:401–408
Lung RW, Tong JH, Sung YM, Leung PS, Ng DC, Chau SL, Chan AW, Ng EK, Lo KW, To KF (2009) Modulation of LMP2A expression by a newly identified Epstein-Barr virus-encoded microRNA miR-BART22. Neoplasia 11:1174–1184
Ma SD, Yu X, Mertz JE, Gumperz JE, Reinheim E, Zhou Y, Tang W, Burlingham WJ, Gulley ML, Kenney SC (2012) An Epstein-Barr Virus (EBV) mutant with enhanced BZLF1 expression causes lymphomas with abortive lytic EBV infection in a humanized mouse model. J Virol 86:7976–7987
Mancao C, Hammerschmidt W (2007) Epstein-Barr virus latent membrane protein 2A is a B-cell receptor mimic and essential for B-cell survival. Blood 110:3715–3721
Mannick JB, Cohen JI, Birkenbach M, Marchini A, Kieff E (1991) The Epstein-Barr virus nuclear protein encoded by the leader of the EBNA RNAs is important in B-lymphocyte transformation. J Virol 65:6826–6837
Marquitz AR, Mathur A, Nam CS, Raab-Traub N (2011) The Epstein-Barr Virus BART microRNAs target the pro-apoptotic protein Bim. Virology 412:392–400
Martin-Subero JI, Ammerpohl O, Bibikova M, Wickham-Garcia E, Agirre X, Alvarez S, Bruggemann M, Bug S, Calasanz MJ, Deckert M, Dreyling M, Du MQ, Durig J, Dyer MJ, Fan JB, Gesk S, Hansmann ML, Harder L, Hartmann S, Klapper W, Kuppers R, Montesinos-Rongen M, Nagel I, Pott C, Richter J, Roman-Gomez J, Seifert M, Stein H, Suela J, Trumper L, Vater I, Prosper F, Haferlach C, Cruz Cigudosa J, Siebert R (2009a) A comprehensive microarray-based DNA methylation study of 367 hematological neoplasms. PLoS One 4:e6986
Martin-Subero JI, Kreuz M, Bibikova M, Bentink S, Ammerpohl O, Wickham-Garcia E, Rosolowski M, Richter J, Lopez-Serra L, Ballestar E, Berger H, Agirre X, Bernd HW, Calvanese V, Cogliatti SB, Drexler HG, Fan JB, Fraga MF, Hansmann ML, Hummel M, Klapper W, Korn B, Kuppers R, Macleod RA, Moller P, Ott G, Pott C, Prosper F, Rosenwald A, Schwaenen C, Schubeler D, Seifert M, Sturzenhofecker B, Weber M, Wessendorf S, Loeffler M, Trumper L, Stein H, Spang R, Esteller M, Barker D, Hasenclever D, Siebert R, Molecular Mechanisms in Malignant Lymphomas Network Project of the Deutsche, K (2009b) New insights into the biology and origin of mature aggressive B-cell lymphomas by combined epigenomic, genomic, and transcriptional profiling. Blood 113:2488–2497
Maruo S, Zhao B, Johannsen E, Kieff E, Zou J, Takada K (2011) Epstein-Barr virus nuclear antigens 3C and 3A maintain lymphoblastoid cell growth by repressing p16INK4A and p14ARF expression. Proc Natl Acad Sci U S A 108:1919–1924
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 latent membrane protein in the Burkitt’s lymphoma line rael. J Virol 63:3135–3141
Matsusaka K, Kaneda A, Nagae G, Ushiku T, Kikuchi Y, Hino R, Uozaki H, Seto Y, Takada K, Aburatani H, Fukayama M (2011) Classification of Epstein-Barr virus-positive gastric cancers by definition of DNA methylation epigenotypes. Cancer Res 71:7187–7197
McClain KL, Leach CT, Jenson HB, Joshi VV, Pollock BH, Parmley RT, DiCarlo FJ, Chadwick EG, Murphy SB (1995) Association of Epstein-Barr virus with leiomyosarcomas in children with AIDS. N Engl J Med 332:12–18
McClellan MJ, Wood CD, Ojeniyi O, Cooper TJ, Kanhere A, Arvey A, Webb HM, Palermo RD, Harth-Hertle ML, Kempkes B, Jenner RG, West MJ (2013) Modulation of enhancer looping and differential gene targeting by Epstein-Barr virus transcription factors directs cellular reprogramming. PLoS Pathog 9:e1003636
Merchant M, Caldwell RG, Longnecker R (2000) The LMP2A ITAM is essential for providing B cells with development and survival signals in vivo. J Virol 74:9115–9124
Minarovits J (2006) Epigenotypes of latent herpesvirus genomes. Curr Top Microbiol Immunol 310:61–80
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(Pt 7):1687–1692
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(Pt 1):77–84
Miyashita EM, Yang B, Babcock GJ, Thorley-Lawson DA (1997) Identification of the site of Epstein-Barr virus persistence in vivo as a resting B cell. J Virol 71:4882–4891
Mo Y, Midorikawa K, Zhang Z, Zhou X, Ma N, Huang G, Hiraku Y, Oikawa S, Murata M (2012) Promoter hypermethylation of Ras-related GTPase gene RRAD inactivates a tumor suppressor function in nasopharyngeal carcinoma. Cancer Lett 323:147–154
Moore GE, Gerner RE, Franklin HA (1967) Culture of normal human leukocytes. JAMA 199:519–524
Morissette G, Flamand L (2010) Herpesviruses and chromosomal integration. J Virol 84:12100–12109
Motsch N, Pfuhl T, Mrazek J, Barth S, Grasser FA (2007) Epstein-Barr virus-encoded latent membrane protein 1 (LMP1) induces the expression of the cellular microRNA miR-146a. RNA Biol 4:131–137
Munz C (2014) Dendritic cells during Epstein Barr virus infection. Front Microbiol 5:308
Nachmani D, Stern-Ginossar N, Sarid R, Mandelboim O (2009) Diverse herpesvirus microRNAs target the stress-induced immune ligand MICB to escape recognition by natural killer cells. Cell Host Microbe 5:376–385
Nagy N, Adori M, Rasul A, Heuts F, Salamon D, Ujvari D, Madapura HS, Leveau B, Klein G, Klein E (2012) Soluble factors produced by activated CD4+ T cells modulate EBV latency. Proc Natl Acad Sci U S A 109:1512–1517
Navari M, Fuligni F, Laginestra MA, Etebari M, Ambrosio MR, Sapienza MR, Rossi M, De Falco G, Gibellini D, Tripodo C, Pileri SA, Leoncini L, Piccaluga PP (2014) Molecular signature of Epstein Barr virus-positive Burkitt lymphoma and post-transplant lymphoproliferative disorder suggest different roles for Epstein Barr virus. Front Microbiol 5:728
Niedobitek G, Agathanggelou A, Herbst H, Whitehead L, Wright DH, Young LS (1997) Epstein-Barr virus (EBV) infection in infectious mononucleosis: virus latency, replication and phenotype of EBV-infected cells. J Pathol 182:151–159
Niller HH, Minarovits J (2012) Similarities between the Epstein-Barr virus (EBV) nuclear protein EBNA1 and the pioneer transcription factor FoxA: is EBNA1 a “bookmarking” oncoprotein that alters the host cell epigenotype? Pathogens 1:37–51
Niller HH, Salamon D, Ilg K, Koroknai A, Banati F, Bauml G, Rucker O, 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
Niller HH, Salamon D, Banati F, Schwarzmann F, Wolf H, Minarovits J (2004a) The LCR of EBV makes Burkitt’s lymphoma endemic. Trends Microbiol 12:495–499
Niller HH, Salamon D, Ilg K, Koroknai A, Banati F, Schwarzmann F, Wolf H, Minarovits J (2004b) EBV-associated neoplasms: alternative pathogenetic pathways. Med Hypotheses 62:387–391
Niller HH, Salamon D, Rahmann S, Ilg K, Koroknai A, Banati F, Schwarzmann F, Wolf H, Minarovits J (2004c) 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. A review. Acta Microbiol Immunol Hung 51:469–484
Niller HH, Wolf H, Minarovits J (2007) Epstein-Barr virus. In: Minarovits J, Gonczol E, Valyi-Nagy T (eds) Latency strategies of herpesviruses. Springer, New York, pp 154–191
Niller HH, Wolf H, Minarovits J (2009) Epigenetic dysregulation of the host cell genome in Epstein-Barr virus-associated neoplasia. Semin Cancer Biol 19:158–164
Niller HH, Wolf H, Ay E, Minarovits J (2011) Epigenetic dysregulation of Epstein-Barr virus latency and development of autoimmune disease. Adv Exp Med Biol 711:82–102
Niller HH, Banati F, Ay E, Minarovits J (2012) Epigenetic changes in virus-associated neoplasms. In: Minarovits J, Niller HH (eds) Patho-epigenetics of disease. Springer, New York, pp 179–225
Niller HH, Banati F, Minarovits J (2014a) Epigenetic alterations in nasopharyngeal carcinoma and Epstein-Barr virus (EBV) associated gastric carcinoma: a lesson in contrasts. J Nasopharyng Carcinoma 1:e9
Niller HH, Szenthe K, Minarovits J (2014b) Epstein-Barr virus-host cell interactions: an epigenetic dialog? Front Genet 5:367
Niller HH, Tarnai Z, Decsi G, Zsedenyi A, Banati F, Minarovits J (2014c) Role of epigenetics in EBV regulation and pathogenesis. Future Microbiol 9:747–756
Nilsson K, Klein G, Henle W, Henle G (1971) The establishment of lymphoblastoid lines from adult and fetal human lymphoid tissue and its dependence on EBV. Int J Cancer 8:443–450
O’Neil JD, Owen TJ, Wood VH, Date KL, Valentine R, Chukwuma MB, Arrand JR, Dawson CW, Young LS (2008) Epstein-Barr virus-encoded EBNA1 modulates the AP-1 transcription factor pathway in nasopharyngeal carcinoma cells and enhances angiogenesis in vitro. J Gen Virol 89:2833–2842
Oudejans JJ, Jiwa M, van den Brule AJ, Grasser FA, Horstman A, Vos W, Kluin PM, van der Valk P, Walboomers JM, Meijer CJ (1995) Detection of heterogeneous Epstein-Barr virus gene expression patterns within individual post-transplantation lymphoproliferative disorders. Am J Pathol 147:923–933
Pajic A, Polack A, Staege MS, Spitkovsky D, Baier B, Bornkamm GW, Laux G (2001) Elevated expression of c-myc in lymphoblastoid cells does not support an Epstein-Barr virus latency III-to-I switch. J Gen Virol 82:3051–3055
Panagopoulos D, Victoratos P, Alexiou M, Kollias G, Mosialos G (2004) Comparative analysis of signal transduction by CD40 and the Epstein-Barr virus oncoprotein LMP1 in vivo. J Virol 78:13253–13261
Paschos K, Parker GA, Watanatanasup E, White RE, Allday MJ (2012) BIM promoter directly targeted by EBNA3C in polycomb-mediated repression by EBV. Nucleic Acids Res 40:7233–7246
Peng D, Ren CP, Yi HM, Zhou L, Yang XY, Li H, Yao KT (2006) Genetic and epigenetic alterations of DLC-1, a candidate tumor suppressor gene, in nasopharyngeal carcinoma. Acta Biochim Biophys Sin (Shanghai) 38:349–355
Pfeffer S, Zavolan M, Grasser FA, Chien M, Russo JJ, Ju J, John B, Enright AJ, Marks D, Sander C, Tuschl T (2004) Identification of virus-encoded microRNAs. Science 304:734–736
Polack A, Hortnagel K, Pajic A, Christoph B, Baier B, Falk M, Mautner J, Geltinger C, Bornkamm GW, Kempkes B (1996) c-myc activation renders proliferation of Epstein-Barr virus (EBV)-transformed cells independent of EBV nuclear antigen 2 and latent membrane protein 1. Proc Natl Acad Sci U S A 93:10411–10416
Pope JH, Horne MK, Scott W (1968) Transformation of foetal human keukocytes in vitro by filtrates of a human leukaemic cell line containing herpes-like virus. Int J Cancer 3:857–866
Portal D, Rosendorff A, Kieff E (2006) Epstein-Barr nuclear antigen leader protein coactivates transcription through interaction with histone deacetylase 4. Proc Natl Acad Sci U S A 103:19278–19283
Qiu GH, Tan LK, Loh KS, Lim CY, Srivastava G, Tsai ST, Tsao SW, Tao Q (2004) The candidate tumor suppressor gene BLU, located at the commonly deleted region 3p21.3, is an E2F-regulated, stress-responsive gene and inactivated by both epigenetic and genetic mechanisms in nasopharyngeal carcinoma. Oncogene 23:4793–4806
Qu L, Rowe DT (1992) Epstein-Barr virus latent gene expression in uncultured peripheral blood lymphocytes. J Virol 66:3715–3724
Raab-Traub N, Flynn K (1986) The structure of the termini of the Epstein-Barr virus as a marker of clonal cellular proliferation. Cell 47:883–889
Rasul E, Salamon D, Nagy N, Leveau B, Banati F, Szenthe K, Koroknai A, Minarovits J, Klein G, Klein E (2014) The MEC1 and MEC2 lines represent two CLL subclones in different stages of progression towards prolymphocytic leukemia. PLoS One 9:e106008
Rickinson AB (2014) Co-infections, inflammation and oncogenesis: future directions for EBV research. Semin Cancer Biol 26:99–115
Riley KJ, Rabinowitz GS, Yario TA, Luna JM, Darnell RB, Steitz JA (2012) EBV and human microRNAs co-target oncogenic and apoptotic viral and human genes during latency. EMBO J 31:2207–2221
Rossi G, Bonetti F (2004) EBV and Burkitt’s lymphoma. N Engl J Med 350:2621
Roughan JE, Torgbor C, Thorley-Lawson DA (2010) Germinal center B cells latently infected with Epstein-Barr virus proliferate extensively but do not increase in number. J Virol 84:1158–1168
Rowe M, Rowe DT, Gregory CD, Young LS, Farrell PJ, Rupani H, Rickinson AB (1987) Differences in B cell growth phenotype reflect novel patterns of Epstein-Barr virus latent gene expression in Burkitt’s lymphoma cells. EMBO J 6:2743–2751
Ruf IK, Rhyne PW, Yang C, Cleveland JL, Sample JT (2000) Epstein-Barr virus small RNAs potentiate tumorigenicity of Burkitt lymphoma cells independently of an effect on apoptosis. J Virol 74:10223–10228
Sakuma K, Chong JM, Sudo M, Ushiku T, Inoue Y, Shibahara J, Uozaki H, Nagai H, Fukayama M (2004) High-density methylation of p14ARF and p16INK4A in Epstein-Barr virus-associated gastric carcinoma. Int J Cancer 112:273–278
Salamon D, Takacs M, Myohanen S, Marcsek Z, Berencsi G, Minarovits J (2000) De novo DNA 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
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
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
Salamon D, Banati F, Koroknai A, Ravasz M, Szenthe K, Bathori Z, Bakos A, Niller HH, Wolf H, Minarovits J (2009) Binding of CCCTC-binding factor in vivo to the region located between Rep* and C-promoter of Epstein-Barr virus is unaffected by CpG methylation and does not correlate with Cp activity. J Gen Virol 90:1183–1189
Sarkari F, Sanchez-Alcaraz T, Wang S, Holowaty MN, Sheng Y, Frappier L (2009) EBNA1-mediated recruitment of a histone H2B deubiquitylating complex to the Epstein-Barr virus latent origin of DNA replication. PLoS Pathog 5:e1000624
Scholle F, Bendt KM, Raab-Traub N (2000) Epstein-Barr virus LMP2A transforms epithelial cells, inhibits cell differentiation, and activates Akt. J Virol 74:10681–10689
Seo SY, Kim EO, Jang KL (2008) Epstein-Barr virus latent membrane protein 1 suppresses the growth-inhibitory effect of retinoic acid by inhibiting retinoic acid receptor-beta2 expression via DNA methylation. Cancer Lett 270:66–76
Seto E, Yang L, Middeldorp J, Sheen TS, Chen JY, Fukayama M, Eizuru Y, Ooka T, Takada K (2005) Epstein-Barr virus (EBV)-encoded BARF1 gene is expressed in nasopharyngeal carcinoma and EBV-associated gastric carcinoma tissues in the absence of lytic gene expression. J Med Virol 76:82–88
Seto E, Moosmann A, Gromminger S, Walz N, Grundhoff A, Hammerschmidt W (2010) Micro RNAs of Epstein-Barr virus promote cell cycle progression and prevent apoptosis of primary human B cells. PLoS Pathog 6:e1001063
Shibata D, Tokunaga M, Uemura Y, Sato E, Tanaka S, Weiss LM (1991) Association of Epstein-Barr virus with undifferentiated gastric carcinomas with intense lymphoid infiltration. Lymphoepithelioma-like carcinoma. Am J Pathol 139:469–474
Skalska L, White RE, Franz M, Ruhmann M, Allday MJ (2010) Epigenetic repression of p16(INK4A) by latent Epstein-Barr virus requires the interaction of EBNA3A and EBNA3C with CtBP. PLoS Pathog 6:e1000951
Skalsky RL, Corcoran DL, Gottwein E, Frank CL, Kang D, Hafner M, Nusbaum JD, Feederle R, Delecluse HJ, Luftig MA, Tuschl T, Ohler U, Cullen BR (2012) The viral and cellular microRNA targetome in lymphoblastoid cell lines. PLoS Pathog 8:e1002484
Smith P (2001) Epstein-Barr virus complementary strand transcripts (CSTs/BARTs) and cancer. Semin Cancer Biol 11:469–476
Smith PR, de Jesus O, Turner D, Hollyoake M, Karstegl CE, Griffin BE, Karran L, Wang Y, Hayward SD, Farrell PJ (2000) Structure and coding content of CST (BART) family RNAs of Epstein-Barr virus. J Virol 74:3082–3092
Sriuranpong V, Mutirangura A, Gillespie JW, Patel V, Amornphimoltham P, Molinolo AA, Kerekhanjanarong V, Supanakorn S, Supiyaphun P, Rangdaeng S, Voravud N, Gutkind JS (2004) Global gene expression profile of nasopharyngeal carcinoma by laser capture microdissection and complementary DNA microarrays. Clin Cancer Res 10:4944–4958
Strockbine LD, Cohen JI, Farrah T, Lyman SD, Wagener F, DuBose RF, Armitage RJ, Spriggs MK (1998) The Epstein-Barr virus BARF1 gene encodes a novel, soluble colony-stimulating factor-1 receptor. J Virol 72:4015–4021
Sudo M, Chong JM, Sakuma K, Ushiku T, Uozaki H, Nagai H, Funata N, Matsumoto Y, Fukayama M (2004) Promoter hypermethylation of E-cadherin and its abnormal expression in Epstein-Barr virus-associated gastric carcinoma. Int J Cancer 109:194–199
Sugden B, Warren N (1989) 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 63:2644–2649
Sugiura M, Imai S, Tokunaga M, Koizumi S, Uchizawa M, Okamoto K, Osato T (1996) Transcriptional analysis of Epstein-Barr virus gene expression in EBV-positive gastric carcinoma: unique viral latency in the tumour cells. Br J Cancer 74:625–631
Sumaya CV, Myers LW, Ellison GW (1980) Epstein-Barr virus antibodies in multiple sclerosis. Arch Neurol 37:94–96
Takacs M, Salamon D, Myohanen S, Li H, Segesdi J, Ujvari D, Uhlig J, Niller HH, Wolf H, Berencsi G, Minarovits J (2001) 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
Takacs M, Segesdi J, Banati F, Koroknai A, Wolf H, Niller HH, Minarovits J (2009) The importance of epigenetic alterations in the development of Epstein-Barr virus-related lymphomas. Mediterr J Hematol Infect Dis 1:e2009012
Takacs M, Banati F, Koroknai A, Segesdi J, Salamon D, Wolf H, Niller HH, Minarovits J (2010) Epigenetic regulation of latent Epstein-Barr virus promoters. Biochim Biophys Acta 1799:228–235
Takada K (2012) Role of EBER and BARF1 in nasopharyngeal carcinoma (NPC) tumorigenesis. Semin Cancer Biol 22:162–165
Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, Yamanaka S (2007) Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 131:861–872
Tang M, Lautenberger JA, Gao X, Sezgin E, Hendrickson SL, Troyer JL, David VA, Guan L, McIntosh CE, Guo X, Zheng Y, Liao J, Deng H, Malasky M, Kessing B, Winkler CA, Carrington M, De The G, Zeng Y, O’Brien SJ (2012) The principal genetic determinants for nasopharyngeal carcinoma in China involve the HLA class I antigen recognition groove. PLoS Genet 8:e1003103
Taylor GS, Long HM, Brooks JM, Rickinson AB, Hislop AD (2015) The immunology of Epstein-Barr virus-induced disease. Annu Rev Immunol 33:787–821
Tempera I, Wiedmer A, Dheekollu J, Lieberman PM (2010) CTCF prevents the epigenetic drift of EBV latency promoter Qp. PLoS Pathog 6:e1001048
Tempera I, Klichinsky M, Lieberman PM (2011) EBV latency types adopt alternative chromatin conformations. PLoS Pathog 7:e1002180
Thorley-Lawson DA (2001) Epstein-Barr virus: exploiting the immune system. Nat Rev Immunol 1:75–82
Thornburg NJ, Kusano S, Raab-Traub N (2004) Identification of Epstein-Barr virus RK-BARF0-interacting proteins and characterization of expression pattern. J Virol 78:12848–12856
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 down-regulation during virus-induced B-cell transformation. J Virol 74:10468–10479
Tobollik S, Meyer L, Buettner M, Klemmer S, Kempkes B, Kremmer E, Niedobitek G, Jungnickel B (2006) Epstein-Barr virus nuclear antigen 2 inhibits AID expression during EBV-driven B-cell growth. Blood 108:3859–3864
Tomkinson B, Kieff E (1992) Use of second-site homologous recombination to demonstrate that Epstein-Barr virus nuclear protein 3B is not important for lymphocyte infection or growth transformation in vitro. J Virol 66:2893–2903
Tomkinson B, Robertson E, Kieff E (1993) Epstein-Barr virus nuclear proteins EBNA-3A and EBNA-3C are essential for B-lymphocyte growth transformation. J Virol 67:2014–2025
Torgbor C, Awuah P, Deitsch K, Kalantari P, Duca KA, Thorley-Lawson DA (2014) A multifactorial role for P. falciparum malaria in endemic Burkitt’s lymphoma pathogenesis. PLoS Pathog 10:e1004170
Toyota M, Ahuja N, Suzuki H, Itoh F, Ohe-Toyota M, Imai K, Baylin SB, Issa JP (1999) Aberrant methylation in gastric cancer associated with the CpG island methylator phenotype. Cancer Res 59:5438–5442
Tsai CN, Tsai CL, Tse KP, Chang HY, Chang YS (2002) The Epstein-Barr virus oncogene product, latent membrane protein 1, induces the downregulation of E-cadherin gene expression via activation of DNA methyltransferases. Proc Natl Acad Sci U S A 99:10084–10089
Tsai CL, Li HP, Lu YJ, Hsueh C, Liang Y, Chen CL, Tsao SW, Tse KP, Yu JS, Chang YS (2006) Activation of DNA methyltransferase 1 by EBV LMP1 Involves c-Jun NH(2)-terminal kinase signaling. Cancer Res 66:11668–11676
Tsao SW, Tsang CM, To KF, Lo KW (2015) The role of Epstein-Barr virus in epithelial malignancies. J Pathol 235:323–333
Tse KP, Su WH, Chang KP, Tsang NM, Yu CJ, Tang P, See LC, Hsueh C, Yang ML, Hao SP, Li HY, Wang MH, Liao LP, Chen LC, Lin SR, Jorgensen TJ, Chang YS, Shugart YY (2009) Genome-wide association study reveals multiple nasopharyngeal carcinoma-associated loci within the HLA region at chromosome 6p21.3. Am J Hum Genet 85:194–203
Uchida J, Yasui T, Takaoka-Shichijo Y, Muraoka M, Kulwichit W, Raab-Traub N, Kikutani H (1999) Mimicry of CD40 signals by Epstein-Barr virus LMP1 in B lymphocyte responses. Science 286:300–303
Ushijima T (2007) Epigenetic field for cancerization. J Biochem Mol Biol 40:142–150
Ushiku T, Chong JM, Uozaki H, Hino R, Chang MS, Sudo M, Rani BR, Sakuma K, Nagai H, Fukayama M (2007) p73 gene promoter methylation in Epstein-Barr virus-associated gastric carcinoma. Int J Cancer 120:60–66
van Beek J, Brink AA, Vervoort MB, van Zijp MJ, Meijer CJ, van den Brule AJ, Middeldorp JM (2003) In vivo transcription of the Epstein-Barr virus (EBV) BamHI-A region without associated in vivo BARF0 protein expression in multiple EBV-associated disorders. J Gen Virol 84:2647–2659
van den Bosch CA (2004) Is endemic Burkitt’s lymphoma an alliance between three infections and a tumour promoter? Lancet Oncol 5:738–746
van den Bosch C (2012) A role for RNA viruses in the pathogenesis of Burkitt’s lymphoma: the need for reappraisal. Adv Hematol 2012:494758
van den Bosch C, Lloyd G (2000) Chikungunya fever as a risk factor for endemic Burkitt’s lymphoma in Malawi. Trans R Soc Trop Med Hyg 94:704–705
Vento-Tormo R, Rodriguez-Ubreva J, Lisio LD, Islam AB, Urquiza JM, Hernando H, Lopez-Bigas N, Shannon-Lowe C, Martinez N, Montes-Moreno S, Piris MA, Ballestar E (2014) NF-kappaB directly mediates epigenetic deregulation of common microRNAs in Epstein-Barr virus-mediated transformation of B-cells and in lymphomas. Nucleic Acids Res 42:11025–11039
Vo QN, Geradts J, Gulley ML, Boudreau DA, Bravo JC, Schneider BG (2002) Epstein-Barr virus in gastric adenocarcinomas: association with ethnicity and CDKN2A promoter methylation. J Clin Pathol 55:669–675
Walls D, Perricaudet M (1991) Novel downstream elements upregulate transcription initiated from an Epstein-Barr virus latent promoter. EMBO J 10:143–151
Wang S, Frappier L (2009) Nucleosome assembly proteins bind to Epstein-Barr virus nuclear antigen 1 and affect its functions in DNA replication and transcriptional activation. J Virol 83:11704–11714
Wang L, Grossman SR, Kieff E (2000) Epstein-Barr virus nuclear protein 2 interacts with p300, CBP, and PCAF histone acetyltransferases in activation of the LMP1 promoter. Proc Natl Acad Sci U S A 97:430–435
Wang K, Yuen ST, Xu J, Lee SP, Yan HH, Shi ST, Siu HC, Deng S, Chu KM, Law S, Chan KH, Chan AS, Tsui WY, Ho SL, Chan AK, Man JL, Foglizzo V, Ng MK, Chan AS, Ching YP, Cheng GH, Xie T, Fernandez J, Li VS, Clevers H, Rejto PA, Mao M, Leung SY (2014) Whole-genome sequencing and comprehensive molecular profiling identify new driver mutations in gastric cancer. Nat Genet 46:573–582
Weiss LM, Strickler JG, Warnke RA, Purtilo DT, Sklar J (1987) Epstein-Barr viral DNA in tissues of Hodgkin’s disease. Am J Pathol 129:86–91
Weiss LM, Movahed LA, Warnke RA, Sklar J (1989) Detection of Epstein-Barr viral genomes in Reed-Sternberg cells of Hodgkin’s disease. N Engl J Med 320:502–506
Wen B, Wu H, Shinkai Y, Irizarry RA, Feinberg AP (2009) Large histone H3 lysine 9 dimethylated chromatin blocks distinguish differentiated from embryonic stem cells. Nat Genet 41:246–250
White RE, Wade-Martins R, James MR (2001) Sequences adjacent to oriP improve the persistence of Epstein-Barr virus-based episomes in B cells. J Virol 75:11249–11252
White RE, Groves IJ, Turro E, Yee J, Kremmer E, Allday MJ (2010) Extensive co-operation between the Epstein-Barr virus EBNA3 proteins in the manipulation of host gene expression and epigenetic chromatin modification. PLoS One 5:e13979
Whittle HC, Brown J, Marsh K, Greenwood BM, Seidelin P, Tighe H, Wedderburn L (1984) T-cell control of Epstein-Barr virus-infected B cells is lost during P. falciparum malaria. Nature 312:449–450
Woisetschlaeger M, Strominger L, Speck SH (1989) Mutually exclusive use of viral promoters in Epstein-Barr virus latently infected lymphocytes. Proc Natl Acad Sci U S A 86:6498–6502
Woisetschlaeger M, Yandava CN, Furmanski LA, Strominger JL, Speck SH (1990) Promoter switching in Epstein-Barr virus during the initial stages of infection of B lymphocytes. Proc Natl Acad Sci U S A 87:1725–1729
Wolf H, zur Hausen H, Becker V (1973) EB viral genomes in epithelial nasopharyngeal carcinoma cells. Nat New Biol 244:245–247
Wong AM, Kong KL, Chen L, Liu M, Wong AM, Zhu C, Tsang JW, Guan XY (2013) Characterization of CACNA2D3 as a putative tumor suppressor gene in the development and progression of nasopharyngeal carcinoma. Int J Cancer 133:2284–2295
Wu DY, Kalpana GV, Goff SP, Schubach WH (1996) Epstein-Barr virus nuclear protein 2 (EBNA2) binds to a component of the human SNF-SWI complex, hSNF5/Ini1. J Virol 70:6020–6028
Wu MS, Shun CT, Wu CC, Hsu TY, Lin MT, Chang MC, Wang HP, Lin JT (2000) Epstein-Barr virus-associated gastric carcinomas: relation to H. pylori infection and genetic alterations. Gastroenterology 118:1031–1038
Xia T, O’Hara A, Araujo I, Barreto J, Carvalho E, Sapucaia JB, Ramos JC, Luz E, Pedroso C, Manrique M, Toomey NL, Brites C, Dittmer DP, Harrington WJ Jr (2008) EBV microRNAs in primary lymphomas and targeting of CXCL-11 by ebv-mir-BHRF1-3. Cancer Res 68:1436–1442
Xiao X, Zhao W, Tian F, Zhou X, Zhang J, Huang T, Hou B, Du C, Wang S, Mo Y, Yu N, Zhou S, You J, Zhang Z, Huang G, Zeng X (2014) Cytochrome b5 reductase 2 is a novel candidate tumor suppressor gene frequently inactivated by promoter hypermethylation in human nasopharyngeal carcinoma. Tumour Biol 35:3755–3763
Yanatatsaneejit P, Chalermchai T, Kerekhanjanarong V, Shotelersuk K, Supiyaphun P, Mutirangura A, Sriuranpong V (2008) Promoter hypermethylation of CCNA1, RARRES1, and HRASLS3 in nasopharyngeal carcinoma. Oral Oncol 44:400–406
Yates JL, Warren N, Sugden B (1985) Stable replication of plasmids derived from Epstein-Barr virus in various mammalian cells. Nature 313:812–815
Yi HM, Li H, Peng D, Zhang HJ, Wang L, Zhao M, Yao KT, Ren CP (2006) Genetic and epigenetic alterations of LTF at 3p21.3 in nasopharyngeal carcinoma. Oncol Res 16:261–272
Ying J, Srivastava G, Hsieh WS, Gao Z, Murray P, Liao SK, Ambinder R, Tao Q (2005) The stress-responsive gene GADD45G is a functional tumor suppressor, with its response to environmental stresses frequently disrupted epigenetically in multiple tumors. Clin Cancer Res 11:6442–6449
Ying J, Li H, Seng TJ, Langford C, Srivastava G, Tsao SW, Putti T, Murray P, Chan AT, Tao Q (2006) Functional epigenetics identifies a protocadherin PCDH10 as a candidate tumor suppressor for nasopharyngeal, esophageal and multiple other carcinomas with frequent methylation. Oncogene 25:1070–1080
You Y, Yang W, Wang Z, Zhu H, Li H, Lin C, Ran Y (2013) Promoter hypermethylation contributes to the frequent suppression of the CDK10 gene in human nasopharyngeal carcinomas. Cell Oncol (Dordr) 36:323–331
Zetterberg H, Borestrom C, Nilsson T, Rymo L (2004) Multiple EBNA1-binding sites within oriPl are required for EBNA1-dependent transactivation of the Epstein-Barr virus C promoter. Int J Oncol 25:693–696
Zhang L, Pagano JS (1999) Interferon regulatory factor 2 represses the Epstein-Barr virus BamHI Q latency promoter in type III latency. Mol Cell Biol 19:3216–3223
Zhang X, Li W, Li H, Ma Y, He G, Tan G (2012) Genomic methylation profiling combined with gene expression microarray reveals the aberrant methylation mechanism involved in nasopharyngeal carcinoma taxol resistance. Anticancer Drugs 23:856–864
Zhao B, Mar JC, Maruo S, Lee S, Gewurz BE, Johannsen E, Holton K, Rubio R, Takada K, Quackenbush J, Kieff E (2011a) Epstein-Barr virus nuclear antigen 3C regulated genes in lymphoblastoid cell lines. Proc Natl Acad Sci U S A 108:337–342
Zhao B, Zou J, Wang H, Johannsen E, Peng CW, Quackenbush J, Mar JC, Morton CC, Freedman ML, Blacklow SC, Aster JC, Bernstein BE, Kieff E (2011b) Epstein-Barr virus exploits intrinsic B-lymphocyte transcription programs to achieve immortal cell growth. Proc Natl Acad Sci U S A 108:14902–14907
Zhao J, Liang Q, Cheung KF, Kang W, Lung RW, Tong JH, To KF, Sung JJ, Yu J (2013b) Genome-wide identification of Epstein-Barr virus-driven promoter methylation profiles of human genes in gastric cancer cells. Cancer 119:304–312
Zheng Z, Pan J, Chu B, Wong YC, Cheung AL, Tsao SW (1999) Downregulation and abnormal expression of E-cadherin and beta-catenin in nasopharyngeal carcinoma: close association with advanced disease stage and lymph node metastasis. Hum Pathol 30:458–466
Zhou Y, Zeng Z, Zhang W, Xiong W, Wu M, Tan Y, Yi W, Xiao L, Li X, Huang C, Cao L, Tang K, Li X, Shen S, Li G (2008) Lactotransferrin: a candidate tumor suppressor-Deficient expression in human nasopharyngeal carcinoma and inhibition of NPC cell proliferation by modulating the mitogen-activated protein kinase pathway. Int J Cancer 123:2065–2072
Zhu JY, Pfuhl T, Motsch N, Barth S, Nicholls J, Grasser F, Meister G (2009) Identification of novel Epstein-Barr virus microRNA genes from nasopharyngeal carcinomas. J Virol 83:3333–3341
zur Hausen A, Brink AA, Craanen ME, Middeldorp JM, Meijer CJ, van den Brule AJ (2000) Unique transcription pattern of Epstein-Barr virus (EBV) in EBV-carrying gastric adenocarcinomas: expression of the transforming BARF1 gene. Cancer Res 60:2745–2748
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2016 Springer International Publishing Switzerland
About this chapter
Cite this chapter
Niller, H.H., Banati, F., Salamon, D., Minarovits, J. (2016). Epigenetic Alterations in Epstein-Barr Virus-Associated Diseases. In: Minarovits, J., Niller, H. (eds) Patho-Epigenetics of Infectious Disease. Advances in Experimental Medicine and Biology, vol 879. Springer, Cham. https://doi.org/10.1007/978-3-319-24738-0_3
Download citation
DOI: https://doi.org/10.1007/978-3-319-24738-0_3
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-24736-6
Online ISBN: 978-3-319-24738-0
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)