Epstein-barr virus: Diseases linked to infection and transformation

Frontiers in Microbiology

Volumn 7, Issue OCT, 2016, Pages

  Jha, Hem C ^a,b   Pei, Yonggang ^a   Robertson, Erle S ^a  

^a UNIVERSITY OF PENNSYLVANIA   (United States)

^b INDIAN INSTITUTE OF TECHNOLOGY INDORE   (India)

Author keywords

B cell; Cancer; EBV; Epithelial cell; Infection; Latency; Lytic; Transformation

Indexed keywords

CYCLOPHOSPHAMIDE; DOXORUBICIN; EPSTEIN BARR VIRUS ANTIGEN; EPSTEIN BARR VIRUS ANTIGEN 1; EPSTEIN BARR VIRUS ANTIGEN 2; LATENT MEMBRANE PROTEIN 1; METHOTREXATE; PREDNISOLONE; PROCARBAZINE; RITUXIMAB; UNTRANSLATED RNA; VINCRISTINE;

BURKITT LYMPHOMA; CARCINOGENESIS; EPSTEIN BARR VIRUS; EPSTEIN BARR VIRUS INFECTION; HAIRY LEUKOPLAKIA; HODGKIN DISEASE; HUMAN; LATENT PERIOD; LATENT VIRUS INFECTION; LYMPHOPROLIFERATIVE DISEASE; NASOPHARYNX CARCINOMA; NONHODGKIN LYMPHOMA; PATHOGENESIS; POSTTRANSPLANT LYMPHOPROLIFERATIVE DISEASE; PRIMARY CENTRAL NERVOUS SYSTEM LYMPHOMA; REVIEW; STOMACH CARCINOMA; VIRUS CELL TRANSFORMATION; VIRUS LOAD; VIRUS REACTIVATION;

EID: 84996868097     PISSN: None     EISSN: 1664302X     Source Type: Journal    
DOI: 10.3389/fmicb.2016.01602     Document Type: Review

References (234)

1. Accardi, R., Fathallah, I., Gruffat, H., Mariggio, G., Le Calvez-Kelm, F., Voegele, C., et al. (2013). Epstein-Barr virus transforming protein LMP-1 alters B cells gene expression by promoting accumulation of the oncoprotein DeltaNp73alpha. PLoS Pathog. 9:e1003186. doi: 10.1371/journal.ppat.1003186
2. Adamson, A. L., Darr, D., Holley-Guthrie, E., Johnson, R. A., Mauser, A., Swenson, J., et al. (2000). Epstein-Barr virus immediate-early proteins BZLF1 and BRLF1 activate the ATF2 transcription factor by increasing the levels of phosphorylated p38 and c-Jun N-terminal kinases. J. Virol. 74, 1224-1233. doi: 10.1128/JVI.74.3.1224-1233.2000
3. Alexander, F. E., Lawrence, D. J., Freeland, J., Krajewski, A. S., Angus, B., Taylor, G. M., et al. (2003). An epidemiologic study of index and family infectious mononucleosis and adult Hodgkin's disease (HD): evidence for a specific association with EBV+ve HD in young adults. Int. J. Cancer 107, 298-302. doi: 10.1002/ijc.11156
4. Allday, M. J. (2009). How does Epstein-Barr virus (EBV) complement the activation of Myc in the pathogenesis of Burkitt's lymphoma? Semin. Cancer Biol. 19, 366-376. doi: 10.1016/j.semcancer.2009.07.007
5. Allen, U., Alfieri, C., Preiksaitis, J., Humar, A., Moore, D., Tapiero, B., et al. (2002). Epstein-Barr virus infection in transplant recipients: summary of a workshop on surveillance, prevention and treatment. Can. J. Infect. Dis. 13, 89-99. doi: 10.1155/2002/634318
6. Amon, W., and Farrell, P. J. (2005). Reactivation of Epstein-Barr virus from latency. Rev. Med. Virol. 15, 149-156. doi: 10.1002/rmv.456
7. Arvanitakis, L., Yaseen, N., and Sharma, S. (1995). Latent membrane protein-1 induces cyclin D2 expression, pRb hyperphosphorylation, and loss of TGF-beta 1-mediated growth inhibition in EBV-positive B cells. J. Immunol. 155, 1047-1056.
8. Bajaj, B. G., Murakami, M., and Robertson, E. S. (2007). Molecular biology of EBV in relationship to AIDS-associated oncogenesis. Cancer Treat. Res. 133, 141-162. doi: 10.1007/978-0-387-46816-7_5
9. Banerjee, S., Lu, J., Cai, Q., Saha, A., Jha, H. C., Dzeng, R. K., et al. (2013). The EBV latent antigen 3C inhibits apoptosis through targeted regulation of interferon regulatory factors 4 and 8. PLoS Pathog. 9:e1003314. doi: 10.1371/journal.ppat.1003314
10. Banerjee, S., Lu, J., Cai, Q., Sun, Z., Jha, H. C., and Robertson, E. S. (2014). EBNA3C augments Pim-1 mediated phosphorylation and degradation of p21 to promote B-cell proliferation. PLoS Pathog. 10:e1004304. doi: 10.1371/journal.ppat.1004304
11. Bechtel, D., Kurth, J., Unkel, C., and Kuppers, R. (2005). Transformation of BCR-deficient germinal-center B cells by EBV supports a major role of the virus in the pathogenesis of Hodgkin and posttransplantation lymphomas. Blood 106, 4345-4350. doi: 10.1182/blood-2005-06-2342
12. Bibas, M., and Antinori, A. (2009). EBV and HIV-Related Lymphoma. Mediterr. J. Hematol. Infect. Dis. 1:e2009032. doi: 10.4084/MJHID.2009.032
13. Boccellato, F., Anastasiadou, E., Rosato, P., Kempkes, B., Frati, L., Faggioni, A., et al. (2007). EBNA2 interferes with the germinal center phenotype by downregulating BCL6 and TCL1 in non-Hodgkin's lymphoma cells. J. Virol. 81, 2274-2282. doi: 10.1128/JVI.01822-06
14. Borestrom, C., Forsman, A., Ruetschi, U., and Rymo, L. (2012). E2F1, ARID3A/Bright and Oct-2 factors bind to the Epstein-Barr virus C promoter, EBNA1 and oriP, participating in long-distance promoter-enhancer interactions. J. Gen. Virol. 93, 1065-1075. doi: 10.1099/vir.0.038752-0
15. Brady, G., MacArthur, G. J., and Farrell, P. J. (2007). Epstein-Barr virus and Burkitt lymphoma. J. Clin. Pathol. 60, 1397-1402.
16. Brooks, L., Yao, Q. Y., Rickinson, A. B., and Young, L. S. (1992). Epstein-Barr virus latent gene transcription in nasopharyngeal carcinoma cells: coexpression of EBNA1, LMP1, and LMP2 transcripts. J. Virol. 66, 2689-2697.
17. Bryant, H., and Farrell, P. J. (2002). Signal transduction and transcription factor modification during reactivation of Epstein-Barr virus from latency. J. Virol. 76, 10290-10298. doi: 10.1128/JVI.76.20.10290-10298.2002
18. Burkitt, D. P., and Nopmid. (1969). Etiology of Burkitt's lymphoma-an alternative hypothesis to a vectored virus. J. Natl. Cancer Inst. 42, 19-28.
19. Cancer Genome Atlas Research Network (2014). Comprehensive molecular characterization of gastric adenocarcinoma. Nature 513, 202-209. doi: 10.1038/nature13480
20. Cao, J. Y., Mansouri, S., and Frappier, L. (2012). Changes in the nasopharyngeal carcinoma nuclear proteome induced by the EBNA1 protein of Epstein-Barr virus reveal potential roles for EBNA1 in metastasis and oxidative stress responses. J. Virol. 86, 382-394. doi: 10.1128/JVI.05648-11
21. Cao, S. M., Simons, M. J., and Qian, C. N. (2011). The prevalence and prevention of nasopharyngeal carcinoma in China. Chin. J. Cancer 30, 114-119. doi: 10.5732/cjc.010.10377
22. Carbone, A., Gloghini, A., and Dotti, G. (2008). EBV-associated lymphoproliferative disorders: classification and treatment. Oncologist 13, 577-585. doi: 10.1634/theoncologist.2008-0036
23. Cardona, D. M., Layne, A., and Lagoo, A. S. (2012). Lymphomas of the gastro-intestinal tract-pathophysiology, pathology, and differential diagnosis. Indian J. Pathol. Microbiol. 55, 1-16. doi: 10.4103/0377-4929.94847
24. Carter, K. L., Cahir-McFarland, E., and Kieff, E. (2002). Epstein-barr virus-induced changes in B-lymphocyte gene expression. J. Virol. 76, 10427-10436. doi: 10.1128/JVI.76.20.10427-10436.2002
25. Cavaliere, R., Petroni, G., Lopes, M. B., and Schiff, D. (2010). Primary central nervous system post-transplantation lymphoproliferative disorder: an international primary central nervous system lymphoma collaborative group report. Cancer 116, 863-870. doi: 10.1002/cncr.24834
26. Cesarman, E., and Mesri, E. A. (2007). Kaposi sarcoma-associated herpesvirus and other viruses in human lymphomagenesis. Curr. Top. Microbiol. Immunol. 312, 263-287.
27. Chang, L. K., Wei, T. T., Chiu, Y. F., Tung, C. P., Chuang, J. Y., Hung, S. K., et al. (2003). Inhibition of Epstein-Barr virus lytic cycle by (-)-epigallocatechin gallate. Biochem. Biophys. Res. Commun. 301, 1062-1068. doi: 10.1016/S0006-291X(03)00067-6
28. Chang, S. S., Lo, Y. C., Chua, H. H., Chiu, H. Y., Tsai, S. C., Chen, J. Y., et al. (2008). Critical role of p53 in histone deacetylase inhibitor-induced Epstein-Barr virus Zta expression. J. Virol. 82, 7745-7751. doi: 10.1128/JVI.02717-07
29. Chang, Y., Tung, C. H., Huang, Y. T., Lu, J., Chen, J. Y., and Tsai, C. H. (1999). Requirement for cell-to-cell contact in Epstein-Barr virus infection of nasopharyngeal carcinoma cells and keratinocytes. J. Virol. 73, 8857-8866.
30. Chau, C. M., Deng, Z., Kang, H., and Lieberman, P. M. (2008). Cell cycle association of the retinoblastoma protein Rb and the histone demethylase LSD1 with the Epstein-Barr virus latency promoter Cp. J. Virol. 82, 3428-3437. doi: 10.1128/JVI.01412-07
31. Chen, H., Huang, J., Wu, F. Y., Liao, G., Hutt-Fletcher, L., and Hayward, S. D. (2005). Regulation of expression of the Epstein-Barr virus BamHI-A rightward transcripts. J. Virol. 79, 1724-1733. doi: 10.1128/JVI.79.3.1724-1733.2005
32. Chen, J. (2012). Roles of the PI3K/Akt pathway in Epstein-Barr virus-induced cancers and therapeutic implications. World J. Virol. 1, 154-161. doi: 10.5501/wjv.v1.i6.154
33. Chen, X. Z., Chen, H., Castro, F. A., Hu, J. K., and Brenner, H. (2015). Epstein-Barr virus infection and gastric cancer: a systematic review. Medicine (Baltimore) 94:e792. doi: 10.1097/MD.0000000000000792
34. Cho, Y. G., Gordadze, A. V., Ling, P. D., and Wang, F. (1999). Evolution of two types of rhesus lymphocryptovirus similar to type 1 and type 2 Epstein-Barr virus. J. Virol. 73, 9206-9212.
35. Choudhuri, T., Verma, S. C., Lan, K., Murakami, M., and Robertson, E. S. (2007). The ATM/ATR signaling effector Chk2 is targeted by Epstein-Barr virus nuclear antigen 3C to release the G2/M cell cycle block. J. Virol. 81, 6718-6730. doi: 10.1128/JVI.00053-07
36. Cohen, J. I., Kimura, H., Nakamura, S., Ko, Y. H., and Jaffe, E. S. (2009). Epstein-Barr virus-associated lymphoproliferative disease in non-immunocompromised hosts: a status report and summary of an international meeting, 8-9 September 2008. Ann. Oncol. 20, 1472-1482. doi: 10.1093/annonc/mdp064
37. Dambaugh, T., Hennessy, K., Chamnankit, L., and Kieff, E. (1984). U2 region of Epstein-Barr virus DNA may encode Epstein-Barr nuclear antigen 2. Proc. Natl. Acad. Sci. U.S.A. 81, 7632-7636. doi: 10.1073/pnas.81.23.7632
38. Davies, M. L., Xu, S., Lyons-Weiler, J., Rosendorff, A., Webber, S. A., Wasil, L. R., et al. (2010). Cellular factors associated with latency and spontaneous Epstein-Barr virus reactivation in B-lymphoblastoid cell lines. Virology 400, 53-67. doi: 10.1016/j.virol.2010.01.002
39. De Laurenzi, V., Costanzo, A., Barcaroli, D., Terrinoni, A., Falco, M., Annicchiarico-Petruzzelli, M., et al. (1998). Two new p73 splice variants, gamma and delta, with different transcriptional activity. J. Exp. Med. 188, 1763-1768. doi: 10.1084/jem.188.9.1763
40. de Martel, C., Ferlay, J., Franceschi, S., Vignat, J., Bray, F., Forman, D., et al. (2012). Global burden of cancers attributable to infections in 2008: a review and synthetic analysis. Lancet Oncol. 13, 607-615. doi: 10.1016/S1470-2045(12)70137-7
41. De Paschale, M., and Clerici, P. (2012). Serological diagnosis of Epstein-Barr virus infection: problems and solutions. World J. Virol. 1, 31-43. doi: 10.5501/wjv.v1.i1.31
42. Delecluse, H. J., and Hammerschmidt, W. (2000). The genetic approach to the Epstein-Barr virus: from basic virology to gene therapy. Mol. Pathol. 53, 270-279. doi: 10.1136/mp.53.5.270
43. de-The, G. (1985). Epstein-Barr virus and Burkitt's lymphoma worldwide: the causal relationship revisited. IARC Sci. Publ. 60, 165-176.
44. Diaz, J. I., Edinger, M. G., Stoler, M., and Tubbs, R. R. (1993). Host tumor infiltrating lymphocytes in B cell non-Hodgkin's lymphomas. Leuk. Lymphoma 9, 85-90. doi: 10.3109/10428199309148508
45. Ding, L., Li, L., Yang, J., Zhou, S., Li, W., Tang, M., et al. (2007). Latent membrane protein 1 encoded by Epstein-Barr virus induces telomerase activity via p16INK4A/Rb/E2F1 and JNK signaling pathways. J. Med. Virol. 79, 1153-1163. doi: 10.1002/jmv.20896
46. Dzeng, R. K., Jha, H. C., Lu, J., Saha, A., Banerjee, S., and Robertson, E. S. (2015). Small molecule growth inhibitors of human oncogenic gammaherpesvirus infected B-cells. Mol. Oncol. 9, 365-376. doi: 10.1016/j.molonc.2014.09.006
47. Edwards, R. H., Marquitz, A. R., and Raab-Traub, N. (2015). Changes in expression induced by Epstein-Barr virus LMP1-CTAR1: potential role of bcl3. MBio 6:e00441-15. doi: 10.1128/mBio.00441-15
48. Ekstrom Smedby, K., Vajdic, C. M., Falster, M., Engels, E. A., Martinez-Maza, O., Turner, J., et al. (2008). Autoimmune disorders and risk of non-Hodgkin lymphoma subtypes: a pooled analysis within the InterLymph consortium. Blood 111, 4029-4038. doi: 10.1182/blood-2007-10-119974
49. Engels, E. A. (2007). Infectious agents as causes of non-Hodgkin lymphoma. Cancer Epidemiol. Biomarkers. Prev. 16, 401-404. doi: 10.1158/1055-9965.EPI-06-1056
50. Epstein, M. A., Achong, B. G., and Barr, Y. M. (1964). Virus particles in cultured lymphoblasts from Burkitt's lymphoma. Lancet 1, 702-703. doi: 10.1016/S0140-6736(64)91524-7
51. Everly, D. N. Jr., Mainou, B. A., and Raab-Traub, N. (2004). Induction of Id1 and Id3 by latent membrane protein 1 of Epstein-Barr virus and regulation of p27/Kip and cyclin-dependent kinase 2 in rodent fibroblast transformation. J. Virol. 78, 13470-13478. doi: 10.1128/JVI.78.24.13470-13478.2004
52. Fagundes, C. P., Jaremka, L. M., Glaser, R., Alfano, C. M., Povoski, S. P., Lipari, A. M., et al. (2014). Attachment anxiety is related to Epstein-Barr virus latency. Brain Behav. Immun. 41, 232-238. doi: 10.1016/j.bbi.2014.04.002
53. Fahmi, H., Cochet, C., Hmama, Z., Opolon, P., and Joab, I. (2000). Transforming growth factor beta 1 stimulates expression of the Epstein-Barr virus BZLF1 immediate-early gene product ZEBRA by an indirect mechanism which requires the MAPK kinase pathway. J. Virol. 74, 5810-5818. doi: 10.1128/JVI.74.13.5810-5818.2000
54. Feederle, R., Haar, J., Bernhardt, K., Linnstaedt, S. D., Bannert, H., Lips, H., et al. (2011). The members of an Epstein-Barr virus microRNA cluster cooperate to transform B lymphocytes. J. Virol. 85, 9801-9810. doi: 10.1128/JVI.05100-11
55. Fink, S. E., Gandhi, M. K., Nourse, J. P., Keane, C., Jones, K., Crooks, P., et al. (2014). A comprehensive analysis of the cellular and EBV-specific microRNAome in primary CNS PTLD identifies different patterns among EBV-associated tumors. Am. J. Transplant. 14, 2577-2587. doi: 10.1111/ajt.12858
56. Flavell, J. R., Baumforth, K. R., Wood, V. H., Davies, G. L., Wei, W., Reynolds, G. M., et al. (2008). Down-regulation of the TGF-beta target gene, PTPRK, by the Epstein-Barr virus encoded EBNA1 contributes to the growth and survival of Hodgkin lymphoma cells. Blood 111, 292-301.
57. Flavell, K. J., and Murray, P. G. (2000). Hodgkin's disease and the Epstein-Barr virus. Mol. Pathol. 53, 262-269. doi: 10.1136/mp.53.5.262
58. Forte, E., and Luftig, M. A. (2009). MDM2-dependent inhibition of p53 is required for Epstein-Barr virus B-cell growth transformation and infected-cell survival. J. Virol. 83, 2491-2499. doi: 10.1128/JVI.01681-08
59. Forte, E., Salinas, R. E., Chang, C., Zhou, T., Linnstaedt, S. D., Gottwein, E., et al. (2012). The Epstein-Barr Virus (EBV)-induced tumor suppressor microRNA MIR-34a is growth promoting in EBV-infected B cells. J. Virol. 86, 6889-6898. doi: 10.1128/JVI.07056-11
60. Frappier, L. (2012a). Contributions of Epstein-Barr nuclear antigen 1 (EBNA1) to cell immortalization and survival. Viruses 4, 1537-1547. doi: 10.3390/v4091537
61. Frappier, L. (2012b). The Epstein-Barr virus EBNA1 protein. Scientifica (Cairo) 2012, 438204. doi: 10.6064/2012/438204
62. Gershburg, E., and Pagano, J. S. (2005). Epstein-Barr virus infections: prospects for treatment. J. Antimicrob. Chemother. 56, 277-281. doi: 10.1093/jac/dki240
63. Giunco, S., Celeghin, A., Gianesin, K., Dolcetti, R., Indraccolo, S., and De Rossi, A. (2015). Cross talk between EBV and telomerase: the role of TERT and NOTCH2 in the switch of latent/lytic cycle of the virus. Cell Death Dis. 6:e1774. doi: 10.1038/cddis.2015.145
64. Givol, I., Givol, D., and Hughes, S. H. (1998). Overexpression of p21waf1/cip1 arrests the growth of chicken embryo fibroblasts that overexpress E2F1. Oncogene 16, 3115-3122. doi: 10.1038/sj.onc.1201849
65. Gorres, K. L., Daigle, D., Mohanram, S., and Miller, G. (2014). Activation and repression of Epstein-Barr virus and Kaposi's sarcoma-associated herpesvirus lytic cycles by short-and medium-chain fatty acids. J. Virol. 88, 8028-8044. doi: 10.1128/JVI.00722-14
66. Goswami, R., Gershburg, S., Satorius, A., and Gershburg, E. (2012). Protein kinase inhibitors that inhibit induction of lytic program and replication of Epstein-Barr virus. Antiviral. Res. 96, 296-304. doi: 10.1016/j.antiviral.2012.09.021
67. Gregory, C. D., Rowe, M., and Rickinson, A. B. (1990). Different Epstein-Barr virus-B cell interactions in phenotypically distinct clones of a Burkitt's lymphoma cell line. J. Gen. Virol. 71(Pt 7), 1481-1495. doi: 10.1099/0022-1317-71-7-1481
68. Gruffat, H., Batisse, J., Pich, D., Neuhierl, B., Manet, E., Hammerschmidt, W., et al. (2002a). Epstein-Barr virus mRNA export factor EB2 is essential for production of infectious virus. J. Virol. 76, 9635-9644. doi: 10.1128/JVI.76.19.9635-9644.2002
69. Gruffat, H., Manet, E., and Sergeant, A. (2002b). MEF2-mediated recruitment of class II HDAC at the EBV immediate early gene BZLF1 links latency and chromatin remodeling. EMBO Rep. 3, 141-146. doi: 10.1093/embo-reports/kvf031
70. Gruhne, B., Sompallae, R., Marescotti, D., Kamranvar, S. A., Gastaldello, S., and Masucci, M. G. (2009). The Epstein-Barr virus nuclear antigen-1 promotes genomic instability via induction of reactive oxygen species. Proc. Natl. Acad. Sci. U.S.A. 106, 2313-2318. doi: 10.1073/pnas.0810619106
71. Grywalska, E., and Rolinski, J. (2015). Epstein-Barr virus-associated lymphomas. Semin. Oncol. 42, 291-303. doi: 10.1053/j.seminoncol.2014.12.030
72. Gstaiger, M., Jordan, R., Lim, M., Catzavelos, C., Mestan, J., Slingerland, J., et al. (2001). Skp2 is oncogenic and overexpressed in human cancers. Proc. Natl. Acad. Sci. U.S.A. 98, 5043-5048. doi: 10.1073/pnas.081474898
73. Gulley, M. L., Raphael, M., Lutz, C. T., Ross, D. W., and Raab-Traub, N. (1992). Epstein-Barr virus integration in human lymphomas and lymphoid cell lines. Cancer 70, 185-191. doi: 10.1002/1097-0142(19920701)70:1<185::AID-CNCR2820700129>3.0.CO;2-J
74. Gulley, M. L., and Tang, W. (2008). Laboratory assays for Epstein-Barr virus-related disease. J. Mol. Diagn. 10, 279-292. doi: 10.2353/jmoldx.2008.080023
75. Gulley, M. L., and Tang, W. (2010). Using Epstein-Barr viral load assays to diagnose, monitor, and prevent posttransplant lymphoproliferative disorder. Clin. Microbiol. Rev. 23, 350-366. doi: 10.1128/CMR.00006-09
76. Gustafson, E. A., Chillemi, A. C., Sage, D. R., and Fingeroth, J. D. (1998). The Epstein-Barr virus thymidine kinase does not phosphorylate ganciclovir or acyclovir and demonstrates a narrow substrate specificity compared to the herpes simplex virus type 1 thymidine kinase. Antimicrob. Agents Chemother. 42, 2923-2931.
77. Haan, K. M., Aiyar, A., and Longnecker, R. (2001). Establishment of latent Epstein-Barr virus infection and stable episomal maintenance in murine B-cell lines. J. Virol. 75, 3016-3020. doi: 10.1128/JVI.75.6.3016-3020.2001
78. Halazonetis, T. D., and Kandil, A. N. (1991). Determination of the c-MYC DNA-binding site. Proc. Natl. Acad. Sci. U.S.A. 88, 6162-6166. doi: 10.1073/pnas.88.14.6162
79. Halder, S., Murakami, M., Verma, S. C., Kumar, P., Yi, F., and Robertson, E. S. (2009). Early events associated with infection of Epstein-Barr virus infection of primary B-cells. PLoS ONE 4:e7214. doi: 10.1371/journal.pone.0007214
80. Harris-Arnold, A., Arnold, C. P., Schaffert, S., Hatton, O., Krams, S. M., Esquivel, C. O., et al. (2015). Epstein-Barr virus modulates host cell microRNA-194 to promote IL-10 production and B lymphoma cell survival. Am. J. Transplant. 15, 2814-2824. doi: 10.1111/ajt.13375
81. Henle, G., Henle, W., and Diehl, V. (1968). Relation of Burkitt's tumor-associated herpes-ytpe virus to infectious mononucleosis. Proc. Natl. Acad. Sci. U.S.A. 59, 94-101. doi: 10.1073/pnas.59.1.94
82. Herrmann, K., Frangou, P., Middeldorp, J., and Niedobitek, G. (2002). Epstein-Barr virus replication in tongue epithelial cells. J. Gen. Virol. 83, 2995-2998. doi: 10.1099/0022-1317-83-12-2995
83. Hislop, A. D., Taylor, G. S., Sauce, D., and Rickinson, A. B. (2007). Cellular responses to viral infection in humans: lessons from Epstein-Barr virus. Annu. Rev. Immunol. 25, 587-617. doi: 10.1146/annurev.immunol.25.022106.141553
84. Hoang, A. T., Lutterbach, B., Lewis, B. C., Yano, T., Chou, T. Y., Barrett, J. F., et al. (1995). A link between increased transforming activity of lymphoma-derived MYC mutant alleles, their defective regulation by p107, and altered phosphorylation of the c-Myc transactivation domain. Mol. Cell. Biol. 15, 4031-4042. doi: 10.1128/MCB.15.8.4031
85. Hofelmayr, H., Strobl, L. J., Marschall, G., Bornkamm, G. W., and Zimber-Strobl, U. (2001). Activated Notch1 can transiently substitute for EBNA2 in the maintenance of proliferation of LMP1-expressing immortalized B cells. J. Virol. 75, 2033-2040. doi: 10.1128/JVI.75.5.2033-2040.2001
86. Hossain, M. S., Iqbal, M. S., Khan, M. A., Rabbani, M. G., Khatun, H., Munira, S., et al. (2014). Diagnosed hematological malignancies in Bangladesh-a retrospective analysis of over 5000 cases from 10 specialized hospitals. BMC Cancer 14:438. doi: 10.1186/1471-2407-14-438
87. Hsieh, W. S., Lemas, M. V., and Ambinder, R. F. (1999). The biology of Epstein-Barr virus in post-transplant lymphoproliferative disease. Transpl. Infect. Dis. 1, 204-212. doi: 10.1034/j.1399-3062.1999.010308.x
88. Hui, K. F., Leung, Y. Y., Yeung, P. L., Middeldorp, J. M., and Chiang, A. K. (2014). Combination of SAHA and bortezomib up-regulates CDKN2A and CDKN1A and induces apoptosis of Epstein-Barr virus-positive Wp-restricted Burkitt lymphoma and lymphoblastoid cell lines. Br. J. Haematol. 167, 639-650. doi: 10.1111/bjh.13089
89. Huo, X., Liu, S., Shao, T., Hua, H., Kong, Q., Wang, J., et al. (2014). GSK3 protein positively regulates type I insulin-like growth factor receptor through forkhead transcription factors FOXO1/3/4. J. Biol. Chem. 289, 24759-24770. doi: 10.1074/jbc.M114.580738
90. Iizasa, H., Nanbo, A., Nishikawa, J., Jinushi, M., and Yoshiyama, H. (2012). Epstein-Barr Virus (EBV)-associated gastric carcinoma. Viruses 4, 3420-3439. doi: 10.3390/v4123420
91. Inman, G. J., and Allday, M. J. (2000). Apoptosis induced by TGF-beta 1 in Burkitt's lymphoma cells is caspase 8 dependent but is death receptor independent. J. Immunol. 165, 2500-2510. doi: 10.4049/jimmunol.165.5.2500
92. Inuzuka, H., Gao, D., Finley, L. W., Yang, W., Wan, L., Fukushima, H., et al. (2012). Acetylation-dependent regulation of Skp2 function. Cell 150, 179-193. doi: 10.1016/j.cell.2012.05.038
93. Issa, I., and Baydoun, H. (2009). Mesenteric panniculitis: various presentations and treatment regimens. World J. Gastroenterol. 15, 3827-3830. doi: 10.3748/wjg.15.3827
94. Jha, H. C., Aj, M., Saha, A., Banerjee, S., Lu, J., and Robertson, E. S. (2014). Epstein-Barr virus essential antigen EBNA3C attenuates H2AX expression. J. Virol. 88, 3776-3788. doi: 10.1128/JVI.03568-13
95. Jha, H. C., Banerjee, S., and Robertson, E. S. (2016). The role of gammaherpesviruses in cancer pathogenesis. Pathogens 5:E18. doi: 10.3390/pathogens5010018
96. Jha, H. C., Lu, J., Saha, A., Cai, Q., Banerjee, S., Prasad, M. A., et al. (2013a). EBNA3C-mediated regulation of aurora kinase B contributes to Epstein-Barr virus-induced B-cell proliferation through modulation of the activities of the retinoblastoma protein and apoptotic caspases. J. Virol. 87, 12121-12138. doi: 10.1128/JVI.02379-13
97. Jha, H. C., Mehta, D., Lu, J., El-Naccache, D., Shukla, S. K., Kovacsics, C., et al. (2015a). Gammaherpesvirus infection of human neuronal cells. MBio 6, e01844-15. doi: 10.1128/mBio.01844-15
98. Jha, H. C., Shukla, S. K., Lu, J., Aj, M. P., Banerjee, S., and Robertson, E. S. (2015b). Dissecting the contribution of EBNA3C domains important for EBV-induced B-cell growth and proliferation. Oncotarget 6, 30115-30129. doi: 10.18632/oncotarget.5002
99. Jha, H. C., Upadhyay, S. K., Prasaed, A. J. M., Lu, J., Cai, Q., Saha, A., et al. (2013b). H2AX phosphorylation is important for LANA-mediated Kaposi's sarcoma-associated herpesvirus episome persistence. J. Virol. 87, 5255-5269. doi: 10.1128/JVI.03575-12
100. Jha, H. C., Yang, K., El-Naccache, D. W., Sun, Z., and Robertson, E. S. (2015c). EBNA3C regulates p53 through induction of Aurora kinase B. Oncotarget 6, 5788-5803. doi: 10.18632/oncotarget.3310
101. Jiang, J. H., Wang, N., Li, A., Liao, W. T., Pan, Z. G., Mai, S. J., et al. (2006). Hypoxia can contribute to the induction of the Epstein-Barr virus (EBV) lytic cycle. J. Clin. Virol. 37, 98-103. doi: 10.1016/j.jcv.2006.06.013
102. Jo, S. H., and Ren, R. (2012). IRF-4 suppresses BCR/ABL transformation of myeloid cells in a DNA binding-independent manner. J. Biol. Chem. 287, 1770-1778. doi: 10.1074/jbc.M111.289728
103. Kaiser, C., Laux, G., Eick, D., Jochner, N., Bornkamm, G. W., and Kempkes, B. (1999). The proto-oncogene c-myc is a direct target gene of Epstein-Barr virus nuclear antigen 2. J. Virol. 73, 4481-4484.
104. Kanakry, J. A., and Ambinder, R. F. (2013). EBV-related lymphomas: new approaches to treatment. Curr. Treat. Options. Oncol. 14, 224-236. doi: 10.1007/s11864-013-0231-y
105. Kanda, A., Kawai, H., Suto, S., Kitajima, S., Sato, S., Takata, T., et al. (2005). Aurora-B/AIM-1 kinase activity is involved in Ras-mediated cell transformation. Oncogene 24, 7266-7272. doi: 10.1038/sj.onc.1208884
106. Kang, M. S., Lee, E. K., Soni, V., Lewis, T. A., Koehler, A. N., Srinivasan, V., et al. (2011). Roscovitine inhibits EBNA1 serine 393 phosphorylation, nuclear localization, transcription, and episome maintenance. J. Virol. 85, 2859-2868. doi: 10.1128/JVI.01628-10
107. Karslioglu, E., Kleinberger, J. W., Salim, F. G., Cox, A. E., Takane, K. K., Scott, D. K., et al. (2011). cMyc is a principal upstream driver of beta-cell proliferation in rat insulinoma cell lines and is an effective mediator of human beta-cell replication. Mol. Endocrinol. 25, 1760-1772. doi: 10.1210/me.2011-1074
108. Kelly, G. L., and Rickinson, A. B. (2007). Burkitt lymphoma: revisiting the pathogenesis of a virus-associated malignancy. Hematology Am. Soc. Hematol. Educ. Program. 2007, 277-284.
109. Kenney, S. C., and Mertz, J. E. (2014). Regulation of the latent-lytic switch in Epstein-Barr virus. Semin. Cancer Biol. 26, 60-68. doi: 10.1016/j.semcancer.2014.01.002
110. Khan, G., and Hashim, M. J. (2014). Global burden of deaths from Epstein-Barr virus attributable malignancies 1990-2010. Infect. Agent Cancer 9:38. doi: 10.1186/1750-9378-9-38
111. Kirchmaier, A. L., and Sugden, B. (1997). Dominant-negative inhibitors of EBNA-1 of Epstein-Barr virus. J. Virol. 71, 1766-1775.
112. Knight, J. S., Sharma, N., and Robertson, E. S. (2005). Epstein-Barr virus latent antigen 3C can mediate the degradation of the retinoblastoma protein through an SCF cellular ubiquitin ligase. Proc. Natl. Acad. Sci. U.S.A. 102, 18562-18566. doi: 10.1073/pnas.0503886102
113. Komatsu, T. L., Rivero, E. R., Gallottini de Magalhaes, M. H., and Nunes, F. D. (2005). Epstein-Barr virus in oral hairy leukoplakia scrapes: identification by PCR. Braz. Oral. Res. 19, 317-321. doi: 10.1590/S1806-83242005000400015
114. Krol, A. D., le Cessie, S., Snijder, S., Kluin-Nelemans, J. C., Kluin, P. M., and Noordijk, E. M. (2003). Primary extranodal non-Hodgkin's lymphoma (NHL): the impact of alternative definitions tested in the Comprehensive Cancer Centre West population-based NHL registry. Ann. Oncol. 14, 131-139.
115. Kuppers, R., and Rajewsky, K. (1998). The origin of Hodgkin and Reed/Sternberg cells in Hodgkin's disease. Annu. Rev. Immunol. 16, 471-493. doi: 10.1146/annurev.immunol.16.1.471
116. Kuriyama, T., Kawano, N., Yamashita, K., and Ueda, A. (2014). Successful treatment of Rituximab-resistant Epstein-Barr virus-associated post-transplant lymphoproliferative disorder using R-CHOP. J. Clin. Exp. Hematop. 54, 149-153. doi: 10.3960/jslrt.54.149
117. Kurth, J., Spieker, T., Wustrow, J., Strickler, G. J., Hansmann, L. M., Rajewsky, K., et al. (2000). EBV-infected B cells in infectious mononucleosis: viral strategies for spreading in the B cell compartment and establishing latency. Immunity 13, 485-495. doi: 10.1016/S1074-7613(00)00048-0
118. Kutok, J. L., and Wang, F. (2006). Spectrum of Epstein-Barr virus-associated diseases. Annu. Rev. Pathol. 1, 375-404. doi: 10.1146/annurev.pathol.1.110304.100209
119. Lahoz, E. G., Xu, L., Schreiber-Agus, N., and DePinho, R. A. (1994). Suppression of Myc, but not E1a, transformation activity by Max-associated proteins, Mad and Mxi1. Proc. Natl. Acad. Sci. U.S.A. 91, 5503-5507. doi: 10.1073/pnas.91.12.5503
120. Lai, K. Y., Chou, Y. C., Lin, J. H., Liu, Y., Lin, K. M., Doong, S. L., et al. (2015). Maintenance of Epstein-Barr virus latent status by a novel mechanism, latent membrane protein 1-Induced interleukin-32, via the protein kinase c-delta Pathway. J. Virol. 89, 5968-5980. doi: 10.1128/JVI.00168-15
121. Laichalk, L. L., and Thorley-Lawson, D. A. (2005). Terminal differentiation into plasma cells initiates the replicative cycle of Epstein-Barr virus in vivo. J. Virol. 79, 1296-1307. doi: 10.1128/JVI.79.2.1296-1307.2005
122. Leao, M., Anderton, E., Wade, M., Meekings, K., and Allday, M. J. (2007). Epstein-barr virus-induced resistance to drugs that activate the mitotic spindle assembly checkpoint in Burkitt's lymphoma cells. J. Virol. 81, 248-260. doi: 10.1128/JVI.01096-06
123. Lewis, J. D. (2012). Risk of lymphoma in patients with inflammatory bowel disease. Gastroenterol. Hepatol. (N Y) 8, 45-47.
124. Lin, J., Jin, X., Page, C., Sondak, V. K., Jiang, G., and Reynolds, R. K. (2000). A modified p53 overcomes mdm2-mediated oncogenic transformation: a potential cancer therapeutic agent. Cancer Res. 60, 5895-5901.
125. Lin, J. C. (2003). Mechanism of action of glycyrrhizic acid in inhibition of Epstein-Barr virus replication in vitro. Antiviral. Res. 59, 41-47. doi: 10.1016/S0166-3542(03)00030-5
126. Lin, J. C., Cherng, J. M., Hung, M. S., Baltina, L. A., Baltina, L., and Kondratenko, R. (2008). Inhibitory effects of some derivatives of glycyrrhizic acid against Epstein-Barr virus infection: structure-activity relationships. Antiviral Res. 79, 6-11. doi: 10.1016/j.antiviral.2008.01.160
127. Liontos, M., Niforou, K., Velimezi, G., Vougas, K., Evangelou, K., Apostolopoulou, K., et al. (2009). Modulation of the E2F1-driven cancer cell fate by the DNA damage response machinery and potential novel E2F1 targets in osteosarcomas. Am. J. Pathol. 175, 376-391. doi: 10.2353/ajpath.2009.081160
128. Liu, M. T., Chang, Y. T., Chen, S. C., Chuang, Y. C., Chen, Y. R., Lin, C. S., et al. (2005). Epstein-Barr virus latent membrane protein 1 represses p53-mediated DNA repair and transcriptional activity. Oncogene 24, 2635-2646. doi: 10.1038/sj.onc.1208319
129. Lozano, R., Naghavi, M., Foreman, K., Lim, S., Shibuya, K., Aboyans, V., et al. (2012). Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet 380, 2095-2128. doi: 10.1016/S0140-6736(12)61728-0
130. Lu, J., Murakami, M., Verma, S. C., Cai, Q., Haldar, S., Kaul, R., et al. (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. doi: 10.1016/j.virol.2010.10.029
131. Ma, J., Sigler, P. B., Xu, Z., and Karplus, M. (2000). A dynamic model for the allosteric mechanism of GroEL. J. Mol. Biol. 302, 303-313. doi: 10.1006/jmbi.2000.4014
132. Macfarlane, L. A., and Murphy, P. R. (2010). MicroRNA: biogenesis, function and role in cancer. Curr. Genomics 11, 537-561. doi: 10.2174/138920210793175895
133. Maddocks, O. D., Berkers, C. R., Mason, S. M., Zheng, L., Blyth, K., Gottlieb, E., et al. (2013). Serine starvation induces stress and p53-dependent metabolic remodelling in cancer cells. Nature 493, 542-546. doi: 10.1038/nature11743
134. Maier, S., Staffler, G., Hartmann, A., Hock, J., Henning, K., Grabusic, K., et al. (2006). Cellular target genes of Epstein-Barr virus nuclear antigen 2. J. Virol. 80, 9761-9771. doi: 10.1128/JVI.00665-06
135. Malinen, M., Jaaskelainen, T., Pelkonen, M., Heikkinen, S., Vaisanen, S., Kosma, V. M., et al. (2013). Proto-oncogene PIM-1 is a novel estrogen receptor target associating with high grade breast tumors. Mol. Cell. Endocrinol. 365, 270-276. doi: 10.1016/j.mce.2012.10.028
136. Mansouri, S., Pan, Q., Blencowe, B. J., Claycomb, J. M., and Frappier, L. (2014). Epstein-Barr virus EBNA1 protein regulates viral latency through effects on let-7 microRNA and dicer. J. Virol. 88, 11166-11177. doi: 10.1128/JVI.01785-14
137. Marquitz, A. R., Mathur, A., Chugh, P. E., Dittmer, D. P., and Raab-Traub, N. (2014). Expression profile of microRNAs in Epstein-Barr virus-infected AGS gastric carcinoma cells. J. Virol. 88, 1389-1393. doi: 10.1128/JVI.02662-13
138. Marquitz, A. R., Mathur, A., Edwards, R. H., and Raab-Traub, N. (2015). Host gene expression is regulated by two types of noncoding RNAs transcribed from the Epstein-Barr virus BamHI A rightward transcript region. J. Virol. 89, 11256-11268. doi: 10.1128/JVI.01492-15
139. Marsh, R. A., and Filipovich, A. H. (2011). Familial hemophagocytic lymphohistiocytosis and X-linked lymphoproliferative disease. Ann. N. Y. Acad. Sci. 1238, 106-121. doi: 10.1111/j.1749-6632.2011.06265.x
140. Martin, H. J., Lee, J. M., Walls, D., and Hayward, S. D. (2007). Manipulation of the toll-like receptor 7 signaling pathway by Epstein-Barr virus. J. Virol. 81, 9748-9758. doi: 10.1128/JVI.01122-07
141. Maynard, S., Schurman, S. H., Harboe, C., de Souza-Pinto, N. C., and Bohr, V. A. (2009). Base excision repair of oxidative DNA damage and association with cancer and aging. Carcinogenesis 30, 2-10. doi: 10.1093/carcin/bgn250
142. Merchant, M., Caldwell, R. G., and Longnecker, R. (2000). The LMP2A ITAM is essential for providing B cells with development and survival signals in vivo. J. Virol. 74, 9115-9124. doi: 10.1128/JVI.74.19.9115-9124.2000
143. Mesri, E. A., Feitelson, M. A., and Munger, K. (2014). Human viral oncogenesis: a cancer hallmarks analysis. Cell Host Microbe 15, 266-282. doi: 10.1016/j.chom.2014.02.011
144. Middeldorp, J. M., Brink, A. A., van den Brule, A. J., and Meijer, C. J. (2003). Pathogenic roles for Epstein-Barr virus (EBV) gene products in EBV-associated proliferative disorders. Crit. Rev. Oncol. Hematol. 45, 1-36. doi: 10.1016/S1040-8428(02)00078-1
145. Mikawa, T., Maruyama, T., Okamoto, K., Nakagama, H., Lleonart, M. E., Tsusaka, T., et al. (2014). Senescence-inducing stress promotes proteolysis of phosphoglycerate mutase via ubiquitin ligase Mdm2. J. Cell Biol. 204, 729-745. doi: 10.1083/jcb.201306149
146. Miller, G., El-Guindy, A., Countryman, J., Ye, J., and Gradoville, L. (2007). Lytic cycle switches of oncogenic human gammaherpesviruses. Adv. Cancer Res. 97, 81-109. doi: 10.1016/S0065-230X(06)97004-3
147. Mochizuki, T., Kitanaka, C., Noguchi, K., Muramatsu, T., Asai, A., and Kuchino, Y. (1999). Physical and functional interactions between Pim-1 kinase and Cdc25A phosphatase. Implications for the Pim-1-mediated activation of the c-Myc signaling pathway. J. Biol. Chem. 274, 18659-18666. doi: 10.1074/jbc.274.26.18659
148. Moscato, M., Boon-Unge, K., and Restrepo, L. (2013). Enhancing brain lesions in a renal transplant patient. Neurohospitalist 3, 15-19. doi: 10.1177/1941874412459333
149. Mosialos, G., Birkenbach, M., Yalamanchili, R., VanArsdale, T., Ware, C., and Kieff, E. (1995). The Epstein-Barr virus transforming protein LMP1 engages signaling proteins for the tumor necrosis factor receptor family. Cell 80, 389-399. doi: 10.1016/0092-8674(95)90489-1
150. Murakami, M., Lan, K., Subramanian, C., and Robertson, E. S. (2005). Epstein-Barr virus nuclear antigen 1 interacts with Nm23-H1 in lymphoblastoid cell lines and inhibits its ability to suppress cell migration. J. Virol. 79, 1559-1568. doi: 10.1128/JVI.79.3.1559-1568.2005
151. Nickoloff, B. J., Qin, J. Z., Chaturvedi, V., Denning, M. F., Bonish, B., and Miele, L. (2002). Jagged-1 mediated activation of notch signaling induces complete maturation of human keratinocytes through NF-kappaB and PPARgamma. Cell Death Differ. 9, 842-855. doi: 10.1038/sj.cdd.4401036
152. Niedobitek, G. (2000). Epstein-Barr virus infection in the pathogenesis of nasopharyngeal carcinoma. Mol. Pathol. 53, 248-254. doi: 10.1136/mp.53.5.248
153. Noh, K. W., Park, J., Joo, E. H., Lee, E. K., Choi, E. Y., and Kang, M. S. (2016). ERK2 phosphorylation of EBNA1 serine 383 residue is important for EBNA1-dependent transactivation. Oncotarget 7, 25507-25515. doi: 10.18632/oncotarget.8177
154. Odumade, O. A., Hogquist, K. A., and Balfour, H. H. Jr. (2011). Progress and problems in understanding and managing primary Epstein-Barr virus infections. Clin. Microbiol. Rev. 24, 193-209. doi: 10.1128/CMR.00044-10
155. Oh, J. K., and Weiderpass, E. (2014). Infection and cancer: global distribution and burden of diseases. Ann. Glob. Health 80, 384-392. doi: 10.1016/j.aogh.2014.09.013
156. O'Neil, J. D., Owen, T. J., Wood, V. H., Date, K. L., Valentine, R., Chukwuma, M. B., et al. (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. doi: 10.1099/vir.0.2008/003392-0
157. Parkin, D. M. (2006). The global health burden of infection-associated cancers in the year 2002. Int. J. Cancer 118, 3030-3044. doi: 10.1002/ijc.21731
158. Pathmanathan, R., Prasad, U., Chandrika, G., Sadler, R., Flynn, K., and Raab-Traub, N. (1995). Undifferentiated, nonkeratinizing, and squamous cell carcinoma of the nasopharynx. Variants of Epstein-Barr virus-infected neoplasia. Am. J. Pathol. 146, 1355-1367.
159. Pegtel, D. M., Middeldorp, J., and Thorley-Lawson, D. A. (2004). Epstein-Barr virus infection in ex vivo tonsil epithelial cell cultures of asymptomatic carriers. J. Virol. 78, 12613-12624. doi: 10.1128/JVI.78.22.12613-12624.2004
160. Penkert, R. R., and Kalejta, R. F. (2011). Tegument protein control of latent herpesvirus establishment and animation. Herpesviridae 2:3. doi: 10.1186/2042-4280-2-3
161. Petrara, M. R., Giunco, S., Serraino, D., Dolcetti, R., and De Rossi, A. (2015). Post-transplant lymphoproliferative disorders: from epidemiology to pathogenesis-driven treatment. Cancer Lett. 369, 37-44. doi: 10.1016/j.canlet.2015.08.007
162. Pfeffer, S., Zavolan, M., Grasser, F. A., Chien, M., Russo, J. J., Ju, J., et al. (2004). Identification of virus-encoded microRNAs. Science 304, 734-736. doi: 10.1126/science.1096781
163. Pirollo, K. F., Hao, Z., Rait, A., Jang, Y. J., Fee, W. E. Jr., Ryan, P., et al. (1997). p53 mediated sensitization of squamous cell carcinoma of the head and neck to radiotherapy. Oncogene 14, 1735-1746. doi: 10.1038/sj.onc.1201116
164. Pisani, P., Parkin, D. M., Munoz, N., and Ferlay, J. (1997). Cancer and infection: estimates of the attributable fraction in 1990. Cancer Epidemiol. Biomarkers Prev. 6, 387-400.
165. Plaxco, K. W., Larson, S., Ruczinski, I., Riddle, D. S., Thayer, E. C., Buchwitz, B., et al. (2000). Evolutionary conservation in protein folding kinetics. J. Mol. Biol. 298, 303-312. doi: 10.1006/jmbi.1999.3663
166. Pope, J. H., Horne, M. K., and 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. doi: 10.1002/ijc.2910030619
167. Prathapam, T., Kuhne, C., and Banks, L. (2002). Skip interacts with the retinoblastoma tumor suppressor and inhibits its transcriptional repression activity. Nucleic Acids Res. 30, 5261-5268. doi: 10.1093/nar/gkf658
168. Ragoczy, T., Heston, L., and Miller, G. (1998). The Epstein-Barr virus Rta protein activates lytic cycle genes and can disrupt latency in B lymphocytes. J. Virol. 72, 7978-7984.
169. Raver, R. M., Panfil, A. R., Hagemeier, S. R., and Kenney, S. C. (2013). The B-cell-specific transcription factor and master regulator Pax5 promotes Epstein-Barr virus latency by negatively regulating the viral immediate early protein BZLF1. J. Virol. 87, 8053-8063. doi: 10.1128/JVI.00546-13
170. Reedman, B. M., and Klein, G. (1973). Cellular localization of an Epstein-Barr virus (EBV)-associated complement-fixing antigen in producer and non-producer lymphoblastoid cell lines. Int. J. Cancer 11, 499-520. doi: 10.1002/ijc.2910110302
171. Reimold, A. M., Iwakoshi, N. N., Manis, J., Vallabhajosyula, P., Szomolanyi-Tsuda, E., Gravallese, E. M., et al. (2001). Plasma cell differentiation requires the transcription factor XBP-1. Nature 412, 300-307. doi: 10.1038/35085509
172. Ren, X., McHale, C. M., Skibola, C. F., Smith, A. H., Smith, M. T., and Zhang, L. (2011). An emerging role for epigenetic dysregulation in arsenic toxicity and carcinogenesis. Environ. Health Perspect. 119, 11-19. doi: 10.1289/ehp.1002114
173. Reusch, J. A., Nawandar, D. M., Wright, K. L., Kenney, S. C., and Mertz, J. E. (2015). Cellular differentiation regulator BLIMP1 induces Epstein-Barr virus lytic reactivation in epithelial and B cells by activating transcription from both the R and Z promoters. J. Virol. 89, 1731-1743. doi: 10.1128/JVI.02781-14
174. Robertson, E. S., Grossman, S., Johannsen, E., Miller, C., Lin, J., Tomkinson, B., et al. (1995). Epstein-Barr virus nuclear protein 3C modulates transcription through interaction with the sequence-specific DNA-binding protein J kappa. J. Virol. 69, 3108-3116.
175. Robertson, E. S., Lin, J., and Kieff, E. (1996). The amino-terminal domains of Epstein-Barr virus nuclear proteins 3A, 3B, and 3C interact with RBPJ(kappa). J. Virol. 70, 3068-3074.
176. Robinson, A. R., Kwek, S. S., and Kenney, S. C. (2012). The B-cell specific transcription factor, Oct-2, promotes Epstein-Barr virus latency by inhibiting the viral immediate-early protein, BZLF1. PLoS Pathog. 8:e1002516. doi: 10.1371/journal.ppat.1002516
177. Rong, L., and Perelson, A. S. (2009). Modeling latently infected cell activation: viral and latent reservoir persistence, and viral blips in HIV-infected patients on potent therapy. PLoS Comput. Biol. 5:e1000533. doi: 10.1371/journal.pcbi.1000533
178. Rooney, C. M., Leen, A. M., Vera, J. F., and Heslop, H. E. (2014). T lymphocytes targeting native receptors. Immunol. Rev. 257, 39-55. doi: 10.1111/imr.12133
179. Ruf, I. K., and Sample, J. (1999). Repression of Epstein-Barr virus EBNA-1 gene transcription by pRb during restricted latency. J. Virol. 73, 7943-7951.
180. Saha, A., Halder, S., Upadhyay, S. K., Lu, J., Kumar, P., Murakami, M., et al. (2011). Epstein-Barr virus nuclear antigen 3C facilitates G1-S transition by stabilizing and enhancing the function of cyclin D1. PLoS Pathog. 7:e1001275. doi: 10.1371/journal.ppat.1001275
181. Saha, A., Jha, H. C., Upadhyay, S. K., and Robertson, E. S. (2015). Epigenetic silencing of tumor suppressor genes during in vitro Epstein-Barr virus infection. Proc. Natl. Acad. Sci. U.S.A. 112, E5199-E5207. doi: 10.1073/pnas.1503806112
182. Saha, A., and Robertson, E. S. (2011). Epstein-Barr virus-associated B-cell lymphomas: pathogenesis and clinical outcomes. Clin. Cancer Res. 17, 3056-3063. doi: 10.1158/1078-0432.CCR-10-2578
183. Saridakis, V., Sheng, Y., Sarkari, F., Holowaty, M. N., Shire, K., Nguyen, T., et al. (2005). Structure of the p53 binding domain of HAUSP/USP7 bound to Epstein-Barr nuclear antigen 1 implications for EBV-mediated immortalization. Mol. Cell 18, 25-36. doi: 10.1016/j.molcel.2005.02.029
184. Seeger, C., and Sohn, J. A. (2014). Targeting hepatitis B virus with CRISPR/Cas9. Mol. Ther. Nucleic Acids 3:e216. doi: 10.1038/mtna.2014.68
185. Shaffer, A. L., Lin, K. I., Kuo, T. C., Yu, X., Hurt, E. M., Rosenwald, A., et al. (2002). Blimp-1 orchestrates plasma cell differentiation by extinguishing the mature B cell gene expression program. Immunity 17, 51-62. doi: 10.1016/S1074-7613(02)00335-7
186. Shair, K. H., Bendt, K. M., Edwards, R. H., Bedford, E. C., Nielsen, J. N., and Raab-Traub, N. (2007). EBV latent membrane protein 1 activates Akt, NFkappaB, and Stat3 in B cell lymphomas. PLoS Pathog. 3:e166. doi: 10.1371/journal.ppat.0030166
187. Shaknovich, R., Basso, K., Bhagat, G., Mansukhani, M., Hatzivassiliou, G., Murty, V. V., et al. (2006). Identification of rare Epstein-Barr virus infected memory B cells and plasma cells in non-monomorphic post-transplant lymphoproliferative disorders and the signature of viral signaling. Haematologica 91, 1313-1320.
188. Shannon-Lowe, C., Adland, E., Bell, A. I., Delecluse, H. J., Rickinson, A. B., and Rowe, M. (2009). Features distinguishing Epstein-Barr virus infections of epithelial cells and B cells: viral genome expression, genome maintenance, and genome amplification. J. Virol. 83, 7749-7760. doi: 10.1128/JVI.00108-09
189. Sharma, M., Mannan, R., Madhukar, M., Navani, S., Manjari, M., Bhasin, T. S., et al. (2014). Immunohistochemical (IHC) analysis of non-Hodgkin's lymphoma (NHL) spectrum according to WHO/REAL classification: a single centre experience from Punjab, India. J. Clin. Diagn. Res. 8, 46-49. doi: 10.7860/JCDR/2014/8173.3988
190. Shibata, D., Tokunaga, M., Uemura, Y., Sato, E., Tanaka, S., and Weiss, L. M. (1991). Association of Epstein-Barr virus with undifferentiated gastric carcinomas with intense lymphoid infiltration. Lymphoepithelioma-like carcinoma. Am. J. Pathol. 139, 469-474.
191. Sivachandran, N., Sarkari, F., and Frappier, L. (2008). Epstein-Barr nuclear antigen 1 contributes to nasopharyngeal carcinoma through disruption of PML nuclear bodies. PLoS Pathog. 4:e1000170. doi: 10.1371/journal.ppat.1000170
192. Speck, S. H., Chatila, T., and Flemington, E. (1997). Reactivation of Epstein-Barr virus: regulation and function of the BZLF1 gene. Trends Microbiol. 5, 399-405. doi: 10.1016/S0966-842X(97)01129-3
193. Spender, L. C., Cannell, E. J., Hollyoake, M., Wensing, B., Gawn, J. M., Brimmell, M., et al. (1999). Control of cell cycle entry and apoptosis in B lymphocytes infected by Epstein-Barr virus. J. Virol. 73, 4678-4688.
194. Spender, L. C., and Inman, G. J. (2011). Inhibition of germinal centre apoptotic programmes by epstein-barr virus. Adv. Hematol. 2011:829525. doi: 10.1155/2011/829525
195. Stuhlmann-Laeisz, C., Borchert, A., Quintanilla-Martinez, L., Hoeller, S., Tzankov, A., Oschlies, I., et al. (2016). In Europe expression of EBNA2 is associated with poor survival in EBV-positive diffuse large B-cell lymphoma of the elderly. Leuk. Lymphoma 57, 39-44. doi: 10.3109/10428194.2015.1040014
196. Subramanian, C., Cotter, M. A. II, and Robertson, E. S. (2001). Epstein-Barr virus nuclear protein EBNA-3C interacts with the human metastatic suppressor Nm23-H1: a molecular link to cancer metastasis. Nat. Med. 7, 350-355. doi: 10.1038/85499
197. Subramanian, D., Bunjobpol, W., and Sabapathy, K. (2015). Interplay between TAp73 protein and selected activator protein-1 (AP-1) family members promotes AP-1 target gene activation and cellular growth. J. Biol. Chem. 290, 18636-18649. doi: 10.1074/jbc.M115.636548
198. Sun, J., Hu, C., Zhu, Y., Sun, R., Fang, Y., Fan, Y., et al. (2015). LMP1 increases expression of NADPH oxidase (NOX) and its regulatory subunit p22 in NP69 nasopharyngeal cells and makes them sensitive to a treatment by a NOX inhibitor. PLoS ONE 10:e0134896. doi: 10.1371/journal.pone.0134896
199. Tanner, J. E., and Alfieri, C. (2001). The Epstein-Barr virus and post-transplant lymphoproliferative disease: interplay of immunosuppression, EBV, and the immune system in disease pathogenesis. Transpl. Infect. Dis. 3, 60-69. doi: 10.1034/j.1399-3062.2001.003002060.x
200. Tao, Q., Robertson, K. D., Manns, A., Hildesheim, A., and Ambinder, R. F. (1998). Epstein-Barr virus (EBV) in endemic Burkitt's lymphoma: molecular analysis of primary tumor tissue. Blood 91, 1373-1381.
201. Taylor, C. R., Russell, R., Lukes, R. J., and Davis, R. L. (1978). An immunohistological study of immunoglobulin content of primary central nervous system lymphomas. Cancer 41, 2197-2205. doi: 10.1002/1097-0142(197806)41:6<2197::AID-CNCR2820410619>3.0.CO;2-2
202. Thompson, M. P., and Kurzrock, R. (2004). Epstein-Barr virus and cancer. Clin. Cancer Res. 10, 803-821. doi: 10.1158/1078-0432.CCR-0670-3
203. Thorley-Lawson, D. A. (2001). Epstein-Barr virus: exploiting the immune system. Nat. Rev. Immunol. 1, 75-82. doi: 10.1038/35095584
204. Tomkinson, B., Robertson, E., and 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.
205. Torre, L. A., Bray, F., Siegel, R. L., Ferlay, J., Lortet-Tieulent, J., and Jemal, A. (2015). Global cancer statistics, 2012. CA Cancer J. Clin. 65, 87-108. doi: 10.3322/caac.21262
206. Tsao, S. W., Tsang, C. M., To, K. F., and Lo, K. W. (2015). The role of Epstein-Barr virus in epithelial malignancies. J. Pathol. 235, 323-333. doi: 10.1002/path.4448
207. Tsimbouri, P., Drotar, M. E., Coy, J. L., and Wilson, J. B. (2002). bcl-xL and RAG genes are induced and the response to IL-2 enhanced in EmuEBNA-1 transgenic mouse lymphocytes. Oncogene 21, 5182-5187. doi: 10.1038/sj.onc.1205490
208. Tsurumi, T., Fujita, M., and Kudoh, A. (2005). Latent and lytic Epstein-Barr virus replication strategies. Rev. Med. Virol. 15, 3-15. doi: 10.1002/rmv.441
209. Tursiella, M. L., Bowman, E. R., Wanzeck, K. C., Throm, R. E., Liao, J., Zhu, J., et al. (2014). Epstein-Barr virus nuclear antigen 3A promotes cellular proliferation by repression of the cyclin-dependent kinase inhibitor p21WAF1/CIP1. PLoS Pathog. 10:e1004415. doi: 10.1371/journal.ppat.1004415
210. Tzellos, S., Correia, P. B., Karstegl, C. E., Cancian, L., Cano-Flanagan, J., McClellan, M. J., et al. (2014). A single amino acid in EBNA-2 determines superior B lymphoblastoid cell line growth maintenance by Epstein-Barr virus type 1 EBNA-2. J. Virol. 88, 8743-8753. doi: 10.1128/JVI.01000-14
211. Valenzuela-Salas, B., Dean-Ferrer, A., and Alamillos-Granados, F. J. (2010). Burkitt's lymphoma: a child's case presenting in the maxilla. Clinical and radiological aspects. Med. Oral. Patol. Oral. Cir. Bucal 15, e479-e482. doi: 10.4317/medoral.15.e479
212. Vockerodt, M., Yap, L. F., Shannon-Lowe, C., Curley, H., Wei, W., Vrzalikova, K., et al. (2015). The Epstein-Barr virus and the pathogenesis of lymphoma. J. Pathol. 235, 312-322. doi: 10.1002/path.4459
213. Vrzalikova, K., Vockerodt, M., Leonard, S., Bell, A., Wei, W., Schrader, A., et al. (2011). Down-regulation of BLIMP1alpha by the EBV oncogene, LMP-1, disrupts the plasma cell differentiation program and prevents viral replication in B cells: implications for the pathogenesis of EBV-associated B-cell lymphomas. Blood 117, 5907-5917. doi: 10.1182/blood-2010-09-307710
214. Walling, D. M., Flaitz, C. M., Nichols, C. M., Hudnall, S. D., and Adler-Storthz, K. (2001). Persistent productive Epstein-Barr virus replication in normal epithelial cells in vivo. J. Infect. Dis. 184, 1499-1507. doi: 10.1086/323992
215. Wang, G. L., Salisbury, E., Shi, X., Timchenko, L., Medrano, E. E., and Timchenko, N. A. (2008). HDAC1 cooperates with C/EBPalpha in the inhibition of liver proliferation in old mice. J. Biol. Chem. 283, 26169-26178. doi: 10.1074/jbc.M803544200
216. Weniger, M. A., and Kuppers, R. (2016). NF-kappaB deregulation in Hodgkin lymphoma. Semin. Cancer Biol. 39, 32-39. doi: 10.1016/j.semcancer.2016.05.001
217. Whitehurst, C. B., Li, G., Montgomery, S. A., Montgomery, N. D., Su, L., and Pagano, J. S. (2015). Knockout of Epstein-Barr virus BPLF1 retards B-cell transformation and lymphoma formation in humanized mice. MBio 6:e01574-15.
218. Wright, D. H. (1971). Burkitt's lymphoma: a review of the pathology, immunology, and possible etiologic factors. Pathol. Annu. 6, 337-363.
219. Wu, Y., Maruo, S., Yajima, M., Kanda, T., and Takada, K. (2007). Epstein-Barr virus (EBV)-encoded RNA 2 (EBER2) but not EBER1 plays a critical role in EBV-induced B-cell growth transformation. J. Virol. 81, 11236-11245. doi: 10.1128/JVI.00579-07
220. Xu, D., Meyer, F., Ehlers, E., Blasnitz, L., and Zhang, L. (2011). Interferon regulatory factor 4 (IRF-4) targets IRF-5 to regulate Epstein-Barr virus transformation. J. Biol. Chem. 286, 18261-18267. doi: 10.1074/jbc.M110.210542
221. Yajima, M., Kanda, T., and Takada, K. (2005). Critical role of Epstein-Barr Virus (EBV)-encoded RNA in efficient EBV-induced B-lymphocyte growth transformation. J. Virol. 79, 4298-4307. doi: 10.1128/JVI.79.7.4298-4307.2005
222. Yamamoto, N., Takizawa, T., Iwanaga, Y., Shimizu, N., and Yamamoto, N. (2000). Malignant transformation of B lymphoma cell line BJAB by Epstein-Barr virus-encoded small RNAs. FEBS Lett. 484, 153-158. doi: 10.1016/S0014-5793(00)02145-1
223. Ye, F., Lei, X., and Gao, S. J. (2011). Mechanisms of Kaposi's sarcoma-associated herpesvirus latency and reactivation. Adv. Virol. 2011:193860. doi: 10.1155/2011/193860
224. Young, L. S., and Dawson, C. W. (2014). Epstein-Barr virus and nasopharyngeal carcinoma. Chin. J. Cancer 33, 581-590. doi: 10.5732/cjc.014.10197
225. Young, L. S., and Rickinson, A. B. (2004). Epstein-Barr virus: 40 years on. Nat. Rev. Cancer 4, 757-768. doi: 10.1038/nrc1452
226. Yuen, K. S., Chan, C. P., Wong, N. H., Ho, C. H., Ho, T. H., Lei, T., et al. (2015). CRISPR/Cas9-mediated genome editing of Epstein-Barr virus in human cells. J. Gen. Virol. 96, 626-636. doi: 10.1099/jgv.0.000012
227. Zalani, S., Coppage, A., Holley-Guthrie, E., and Kenney, S. (1997). The cellular YY1 transcription factor binds a cis-acting, negatively regulating element in the Epstein-Barr virus BRLF1 promoter. J. Virol. 71, 3268-3274.
228. Zebboudj, A., Maroui, M. A., Dutrieux, J., Touil-Boukoffa, C., Bourouba, M., Chelbi-Alix, M. K., et al. (2014). Sodium arsenite induces apoptosis and Epstein-Barr virus reactivation in lymphoblastoid cells. Biochimie 107(Pt. B), 247-256. doi: 10.1016/j.biochi.2014.09.002
229. Zhang, G., Zong, J., Lin, S., Verhoeven, R. J., Tong, S., Chen, Y., et al. (2015). Circulating Epstein-Barr virus microRNAs miR-BART7 and miR-BART13 as biomarkers for nasopharyngeal carcinoma diagnosis and treatment. Int. J. Cancer 136, E301-E312. doi: 10.1002/ijc.29206
230. Zhang, L., and Pagano, J. S. (2001). Interferon regulatory factor 7: a key cellular mediator of LMP-1 in EBV latency and transformation. Semin. Cancer Biol. 11, 445-453. doi: 10.1006/scbi.2001.0411
231. Zhang, Z., Wang, H., Li, M., Rayburn, E. R., Agrawal, S., and Zhang, R. (2005). Stabilization of E2F1 protein by MDM2 through the E2F1 ubiquitination pathway. Oncogene 24, 7238-7247. doi: 10.1038/sj.onc.1208814
232. Zhao, Y., Xu, D., Jiang, Y., and Zhang, L. (2010). Dual functions of interferon regulatory factors 7C in Epstein-Barr virus-mediated transformation of human B lymphocytes. PLoS ONE 5:e9459. doi: 10.1371/journal.pone.0009459
233. Zhou, J., Chau, C. M., Deng, Z., Shiekhattar, R., Spindler, M. P., Schepers, A., et al. (2005). Cell cycle regulation of chromatin at an origin of DNA replication. EMBO J. 24, 1406-1417. doi: 10.1038/sj.emboj.7600609
234. Zhou, S., Fujimuro, M., Hsieh, J. J., Chen, L., and Hayward, S. D. (2000). A role for SKIP in EBNA2 activation of CBF1-repressed promoters. J. Virol. 74, 1939-1947. doi: 10.1128/JVI.74.4.1939-1947.2000