Regulation of the latent-lytic switch in Epstein-Barr virus

Seminars in Cancer Biology

Volumn 26, Issue , 2014, Pages 60-68

  Kenney, Shannon C ^a,b   Mertz, Janet E ^a,b  

^a UNIVERSITY OF WISCONSIN MADISON   (United States)

^b UNIVERSITY OF WISCONSIN SCHOOL OF MEDICINE AND PUBLIC HEALTH   (United States)

Author keywords

Ataxia telangiectasia mutated (ATM); Genome methylation; Hypoxia; Lytic induction therapy; TGF

Indexed keywords

CYCLOPHOSPHAMIDE; DNA; GANCICLOVIR; GEMCITABINE; TRANSFORMING GROWTH FACTOR BETA; VALPROIC ACID; ONCOLYTIC VIRUS; ATM PROTEIN; FATTY ACID BINDING PROTEIN; HAPTOCORRIN; VIRUS PROTEIN;

B LYMPHOCYTE; BRLF1 GENE; BURKITT LYMPHOMA; BZLF1 GENE; CELL ACTIVATION; CELL DIFFERENTIATION; DISEASE ASSOCIATION; DNA DAMAGE; DNA METHYLATION; EPITHELIUM CELL; EPSTEIN BARR VIRUS; EPSTEIN BARR VIRUS INFECTION; GENETIC TRANSCRIPTION; HODGKIN DISEASE; HUMAN; NASOPHARYNX CANCER; NONHUMAN; REGULATORY MECHANISM; REVIEW; SIGNAL TRANSDUCTION; VIRUS GENE; VIRUS REACTIVATION; ANIMAL; GENE EXPRESSION REGULATION; NEOPLASMS; ONCOLYTIC VIROTHERAPY; PHYSIOLOGY; VIROLOGY; VIRUS ACTIVATION; VIRUS GENOME; VIRUS LATENCY; VIRUS REPLICATION; CANCER THERAPY; GENE EXPRESSION; LATENT VIRUS INFECTION; LYTIC INDUCTION THERAPY; LYTIC VIRUS INFECTION; METHYLATION; PLASMA CELL; PROMOTER REGION; PROTEIN EXPRESSION; PROTEIN FUNCTION; VIRUS CELL INTERACTION; VIRUS INFECTION;

ANIMALS; DNA METHYLATION; EPSTEIN-BARR VIRUS INFECTIONS; GENE EXPRESSION REGULATION, VIRAL; GENOME, VIRAL; HERPESVIRUS 4, HUMAN; HUMANS; NEOPLASMS; ONCOLYTIC VIROTHERAPY; ONCOLYTIC VIRUSES; VIRUS ACTIVATION; VIRUS LATENCY; VIRUS REPLICATION;

EID: 84901852108     PISSN: 1044579X     EISSN: 10963650     Source Type: Journal    
DOI: 10.1016/j.semcancer.2014.01.002     Document Type: Review

References (104)

1. Rickinson A., Kieff E. Epstein-Barr virus. Fields Virol. 2006, 2655-2700. Lippincott Williams & Wilkins, Philadelphia, PA. D. Knipe, P. Howley (Eds.).
2. Kieff E., Rickinson A. Epstein-Barr virus and its replication. Fields Virology 2006, 2603-2654. Lippincott Williams & Wilkins, Philadelphia, PA.
3. Hong G.K., Gulley M.L., Feng W.-H., Delecluse H.-J., Holley-Guthrie E., Kenney S.C. Epstein-Barr virus lytic infection contributes to lymphoproliferative disease in a SCID mouse model. J Virol 2005, 79:13993-14003.
4. Hong G.K., Kumar P., Wang L., Damania B., Gulley M.L., Delecluse H.-J., et al. Epstein-Barr virus lytic infection is required for efficient production of the angiogenesis factor vascular endothelial growth factor in lymphoblastoid cell lines. J Virol 2005, 79:13984-13992.
5. Ma S.-D., Hegde S., Young K.H., Sullivan R., Rajesh D., Zhou Y., et al. A new model of Epstein-Barr virus infection reveals an important role for early lytic viral protein expression in the development of lymphomas. J Virol 2011, 85:165-177.
6. Lau R., Middeldorp J., Farrell P.J. Epstein-Barr virus gene expression in oral hairy leukoplakia. Virology 1993, 195:463-474.
7. Frangou P., Buettner M., Niedobitek G. Epstein-Barr virus (EBV) infection in epithelial cells in vivo: rare detection of EBV replication in tongue mucosa but not in salivary glands. J Infect Dis 2005, 191:238-242.
8. Laichalk L.L., Thorley-Lawson D.A. Terminal differentiation into plasma cells initiates the replicative cycle of Epstein-Barr virus in vivo. J Virol 2005, 79:1296-1307.
9. Takada K., Ono Y. Synchronous and sequential activation of latently infected Epstein-Barr virus genomes. J Virol 1989, 63:445-449.
10. Jiang J.-H., Wang N., Li A., Liao W.-T., Pan Z.-G., Mai S.-J., et al. Hypoxia can contribute to the induction of the Epstein-Barr virus (EBV) lytic cycle. J Clin Virol 2006, 37:98-103.
11. Di Renzo L., Alttok A., Klein G., Klein E. Endogenous TGF-β contributes to the induction of the EBV lytic cycle in two burkitt lymphoma cell lines. Int J Cancer 1994, 57:914-919.
12. Fahmi H., Cochet C., Hmama Z., Opolon P., Joab I. 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 2000, 74:5810-5818.
13. Iempridee T., Das S., Xu I., Mertz J.E. Transforming growth factor β-induced reactivation of Epstein-Barr virus involves multiple Smad-binding elements cooperatively activating expression of the latent-lytic switch BZLF1 gene. J Virol 2011, 85:7836-7848.
14. Speck S.H., Chatila T., Flemington E. Reactivation of Epstein-Barr virus: regulation and function of the BZLF1 gene. Trends Microbiol 1997, 5:399-405.
15. Israel B.F., Kenney S.C. Virally targeted therapies for EBV-associated malignancies. Oncogene 2003, 22:5122-5130.
16. Amon W., Farrell P.J. Reactivation of Epstein-Barr virus from latency. Rev Med Virol 2005, 15:149-156.
17. Kenney S., Theodore E. Woodward Award: development of novel, EBV-targeted therapies for EBV-positive tumors. Trans Am Clin Climatol Assoc 2006, 117:55-73. discussion 73-74.
18. Speck S.H., Ganem D. Viral latency and its regulation: lessons from the γ-herpesviruses. Cell Host Microbe 2010, 8:100-115.
19. Lin Z., Flemington E.K. miRNAs in the pathogenesis of oncogenic human viruses. Cancer Lett 2011, 305:186-199.
20. Forte E., Luftig M.A. The role of microRNAs in Epstein-Barr virus latency and lytic reactivation. Microbes Infect Inst Pasteur 2011, 13:1156-1167.
21. Zhu Y., Haecker I., Yang Y., Gao S.-J., Renne R. γ-Herpesvirus-encoded miRNAs and their roles in viral biology and pathogenesis. Curr Opin Virol 2013, 3:1-10.
22. Chen H.-S., Lu F., Lieberman P.M. Epigenetic regulation of EBV and KSHV latency. Curr Opin Virol 2013, 3:251-259.
23. Petosa C., Morand P., Baudin F., Moulin M., Artero J.-B., Müller C.W. Structural basis of lytic cycle activation by the Epstein-Barr virus ZEBRA protein. Mol Cell 2006, 21:565-572.
24. Feederle R., Kost M., Baumann M., Janz A., Drouet E., Hammerschmidt W., et al. The Epstein-Barr virus lytic program is controlled by the co-operative functions of two transactivators. EMBO J 2000, 19:3080-3089.
25. Wille C.K., Nawandar D.M., Panfil A.R., Ko M.M., Hagemeier S.R., Kenney S.C. Viral genome methylation differentially affects the ability of BZLF1 versus BRLF1 to activate Epstein-Barr virus lytic gene expression and viral replication. J Virol 2013, 87:935-950.
26. El-Guindy A., Heston L., Delecluse H.-J., Miller G. Phosphoacceptor site S173 in the regulatory domain of Epstein-Barr virus ZEBRA protein is required for lytic DNA replication but not for activation of viral early genes. J Virol 2007, 81:3303-3316.
27. Heilmann A.M.F., Calderwood M.A., Portal D., Lu Y., Johannsen E. Genome-wide analysis of Epstein-Barr virus Rta DNA binding. J Virol 2012, 86:5151-5164.
28. Adamson A.L., Darr D., Holley-Guthrie E., Johnson R.A., Mauser A., Swenson J., et al. 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 2000, 74:1224-1233.
29. Darr C.D., Mauser A., Kenney S. Epstein-Barr virus immediate-early protein BRLF1 induces the lytic form of viral replication through a mechanism involving phosphatidylinositol-3 kinase activation. J Virol 2001, 75:6135-6142.
30. Ragoczy T., Miller G. Autostimulation of the Epstein-Barr virus BRLF1 promoter is mediated through consensus Sp1 and Sp3 binding sites. J Virol 2001, 75:5240-5251.
31. Chang L.-K., Chung J.-Y., Hong Y.-R., Ichimura T., Nakao M., Liu S.-T. Activation of Sp1-mediated transcription by Rta of Epstein-Barr virus via an interaction with MCAF1. Nucleic Acids Res 2005, 33:6528-6539.
32. Robinson A.R., Kwek S.S., Hagemeier S.R., Wille C.K., Kenney S.C. Cellular transcription factor Oct-1 interacts with the Epstein-Barr virus BRLF1 protein to promote disruption of viral latency. J Virol 2011, 85:8940-8953.
33. Hong G.K., Delecluse H.-J., Gruffat H., Morrison T.E., Feng W.-H., Sergeant A., et al. The BRRF1 early gene of Epstein-Barr virus encodes a transcription factor that enhances induction of lytic infection by BRLF1. J Virol 2004, 78:4983-4992.
34. Hagemeier S.R., Barlow E.A., Kleman A.A., Kenney S.C. The Epstein-Barr virus BRRF1 protein, Na, induces lytic infection in a TRAF2- and p53-dependent manner. J Virol 2011, 85:4318-4329.
35. Calderwood M.A., Holthaus A.M., Johannsen E. The Epstein-Barr virus LF2 protein inhibits viral replication. J Virol 2008, 82:8509-8519.
36. Liu S., Liu P., Borras A., Chatila T., Speck S.H. Cyclosporin A-sensitive induction of the Epstein-Barr virus lytic switch is mediated via a novel pathway involving a MEF2 family member. EMBO J 1997, 16:143-153.
37. Gruffat H., Manet E., Sergeant A. MEF2-mediated recruitment of class II HDAC at the EBV immediate early gene BZLF1 links latency and chromatin remodeling. EMBO Rep 2002, 3:141-146.
38. Kraus R.J., Perrigoue J.G., Mertz J.E. ZEB negatively regulates the lytic-switch BZLF1 gene promoter of Epstein-Barr virus. J Virol 2003, 77:199-207.
39. Yu X., Wang Z., Mertz J.E. ZEB1 regulates the latent-lytic switch in infection by Epstein-Barr virus. PLoS Pathog 2007, 3:e194.
40. Ellis A.L., Wang Z., Yu X., Mertz J.E. Either ZEB1 or ZEB2/SIP1 can play a central role in regulating the Epstein-Barr virus latent-lytic switch in a cell-type-specific manner. J Virol 2010, 84:6139-6152.
41. Yu X., McCarthy P.J., Wang Z., Gorlen D.A., Mertz J.E. Shutoff of BZLF1 gene expression is necessary for immortalization of primary B cells by Epstein-Barr virus. J Virol 2012, 86:8086-8096.
42. Feng W., Kraus R.J., Dickerson S.J., Lim H.J., Jones R.J., Yu X., et al. ZEB1 and c-Jun levels contribute to the establishment of highly lytic Epstein-Barr virus infection in gastric AGS cells. J Virol 2007, 81:10113-10122.
43. Ellis-Connell A.L., Iempridee T., Xu I., Mertz J.E. Cellular microRNAs 200b and 429 regulate the Epstein-Barr virus switch between latency and lytic replication. J Virol 2010, 84:10329-10343.
44. Lin Z., Wang X., Fewell C., Cameron J., Yin Q., Flemington E.K. Differential expression of the miR-200 family microRNAs in epithelial and B cells and regulation of Epstein-Barr virus reactivation by the miR-200 family member miR-429. J Virol 2010, 84:7892-7897.
45. Skalsky R.L., Corcoran D.L., Gottwein E., Frank C.L., Kang D., Hafner M., et al. The viral and cellular microRNA targetome in lymphoblastoid cell lines. PLoS Pathog 2012, 8:e1002484.
46. Riley K.J., Rabinowitz G.S., Yario T.A., Luna J.M., Darnell R.B., Steitz J.A. EBV and human microRNAs co-target oncogenic and apoptotic viral and human genes during latency. EMBO J 2012, 31:2207-2221.
47. Postigo A.A., Depp J.L., Taylor J.J., Kroll K.L. Regulation of Smad signaling through a differential recruitment of coactivators and corepressors by ZEB proteins. EMBO J 2003, 22:2453-2462.
48. Thomas C., Dankesreiter A., Wolf H., Schwarzmann F. The BZLF1 promoter of Epstein-Barr virus is controlled by E box-/HI-motif-binding factors during virus latency. J Gen Virol 2003, 84:959-964.
49. Yu X., McCarthy P.J., Lim H.-J., Iempridee T., Kraus R.J., Gorlen D.A., et al. The ZIIR element of the Epstein-Barr virus BZLF1 promoter plays a central role in establishment and maintenance of viral latency. J Virol 2011, 85:5081-5090.
50. Ma S.-D., Yu X., Mertz J.E., Gumperz J.E., Reinheim E., Zhou Y., et al. An Epstein-Barr virus (EBV) mutant with enhanced BZLF1 expression causes lymphomas with abortive lytic EBV infection in a humanized mouse model. J Virol 2012, 86:7976-7987.
51. Zalani S., Coppage A., Holley-Guthrie E., Kenney S. The cellular YY1 transcription factor binds a cis-acting, negatively regulating element in the Epstein-Barr virus BRLF1 promoter. J Virol 1997, 71:3268-3274.
52. Reusch JR, Nawandar DM, Kenney SC, Mertz JE. Unpublished data. n.d.
53. Nawandar DM, Kenney SC. Unpublished data. n.d.
54. Crook T., Nicholls J.M., Brooks L., O'Nions J., Allday M.J. High level expression of δN-p63: a mechanism for the inactivation of p53 in undifferentiated nasopharyngeal carcinoma (NPC)?. Oncogene 2000, 19:3439-3444.
55. Tsang C.M., Yip Y.L., Lo K.W., Deng W., To K.F., Hau P.M., et al. Cyclin D1 overexpression supports stable EBV infection in nasopharyngeal epithelial cells. Proc Natl Acad Sci U S A 2012, 109:E3473-E3482.
56. Robinson A.R., Kwek S.S., Kenney S.C. The B-cell specific transcription factor, Oct-2, promotes Epstein-Barr virus latency by inhibiting the viral immediate-early protein, BZLF1. PLoS Pathog 2012, 8:e1002516.
57. Raver R.M., Panfil A.R., Hagemeier S.R., Kenney S.C. The B-cell specific transcription factor and master regulator, Pax5, promotes EBV latency by negatively regulating the viral immediate early protein, BZLF1. J Virol 2013.
58. Davies M.L., Xu S., Lyons-Weiler J., Rosendorff A., Webber S.A., Wasil L.R., et al. Cellular factors associated with latency and spontaneous Epstein-Barr virus reactivation in B-lymphoblastoid cell lines. Virology 2010, 400:53-67.
59. Iempridee T, Reusch JR, Riching A, Johannsen E, Dovat S, Kenney SC, et al. submitted. n.d.
60. Hagemeier S.R., Dickerson S.J., Meng Q., Yu X., Mertz J.E., Kenney S.C. Sumoylation of the Epstein-Barr virus BZLF1 protein inhibits its transcriptional activity and is regulated by the virus-encoded protein kinase. J Virol 2010, 84:4383-4394.
61. Bryant H., Farrell P.J. Signal transduction and transcription factor modification during reactivation of Epstein-Barr virus from latency. J Virol 2002, 76:10290-10298.
62. Goswami R., Gershburg S., Satorius A., Gershburg E. Protein kinase inhibitors that inhibit induction of lytic program and replication of Epstein-Barr virus. Antiviral Res 2012, 96:296-304.
63. Matthews S.A., Liu P., Spitaler M., Olson E.N., McKinsey T.A., Cantrell D.A., et al. Essential role for protein kinase D family kinases in the regulation of class II histone deacetylases in B lymphocytes. Mol Cell Biol 2006, 26:1569-1577.
64. Sun C.C., Thorley-Lawson D.A. Plasma cell-specific transcription factor XBP-1s binds to and transactivates the Epstein-Barr virus BZLF1 promoter. J Virol 2007, 81:13566-13577.
65. Shirley C.M., Chen J., Shamay M., Li H., Zahnow C.A., Hayward S.D., et al. Bortezomib induction of C/EBPβ mediates Epstein-Barr virus lytic activation in Burkitt lymphoma. Blood 2011, 117:6297-6303.
66. Liang C.-L., Chen J.-L., Hsu Y.-P.P., Ou J.T., Chang Y.-S. Epstein-Barr virus BZLF1 gene is activated by transforming growth factor-β through cooperativity of Smads and c-Jun/c-Fos proteins. J Biol Chem 2002, 277:23345-23357.
67. Oussaief L., Ramírez V., Hippocrate A., Arbach H., Cochet C., Proust A., et al. NF-κB-mediated modulation of inducible nitric oxide synthase activity controls induction of the Epstein-Barr virus productive cycle by transforming growth factor beta 1. J Virol 2011, 85:6502-6512.
68. Ye J., Gradoville L., Miller G. Cellular immediate-early gene expression occurs kinetically upstream of Epstein-Barr virus BZLF1 and BRLF1 following cross-linking of the B cell antigen receptor in the Akata Burkitt lymphoma cell line. J Virol 2010, 84:12405-12418.
69. Zalani S., Holley-Guthrie E., Kenney S. The Zif268 cellular transcription factor activates expression of the Epstein-Barr virus immediate-early BRLF1 promoter. J Virol 1995, 69:3816-3823.
70. Vockerodt M., Wei W., Nagy E., Prouzova Z., Schrader A., Kube D., et al. Suppression Of The LMP2A target gene, EGR-1, protects Hodgkin's lymphoma cells from entry to the EBV lytic cycle. J Pathol 2013, n/a-n/a.
71. Quiñones A., Dobberstein K.U., Rainov N.G. The EGR-1 gene is induced by DNA-damaging agents and non-genotoxic drugs in both normal and neoplastic human cells. Life Sci 2003, 72:2975-2992.
72. Chang Y., Lee H.-H., Chen Y.-T., Lu J., Wu S.-Y., Chen C.-W., et al. Induction of the early growth response 1 gene by Epstein-Barr virus lytic transactivator Zta. J Virol 2006, 80:7748-7755.
73. Heather J., Flower K., Isaac S., Sinclair A.J. The Epstein-Barr virus lytic cycle activator Zta interacts with methylated ZRE in the promoter of host target gene EGR1. J Gen Virol 2009, 90:1450-1454.
74. Feng W., Hong G., Delecluse H.-J., Kenney S.C. Lytic induction therapy for Epstein-Barr virus-positive B-cell lymphomas. J Virol 2004, 78:1893-1902.
75. Kraus RJ, Yu X, Sathiamoorthi S, Ruegsegger N, Nawandar DM, Kenney SC, et al. Unpublished data. n.d.
76. Hagemeier S.R., Barlow E.A., Meng Q., Kenney S.C. The cellular ataxia telangiectasia-mutated kinase promotes Epstein-Barr virus lytic reactivation in response to multiple different types of lytic reactivation-inducing stimuli. J Virol 2012, 86:13360-13370.
77. Chang S.-S., Lo Y.-C., Chua H.-H., Chiu H.-Y., Tsai S.-C., Chen J.-Y., et al. Critical role of p53 in histone deacetylase inhibitor-induced Epstein-Barr virus Zta expression. J Virol 2008, 82:7745-7751.
78. Yu J., Baron V., Mercola D., Mustelin T., Adamson E.D. A network of p73, p53 and Egr1 is required for efficient apoptosis in tumor cells. Cell Death Differ 2006, 14:436-446.
79. Bhende P.M., Dickerson S.J., Sun X., Feng W.-H., Kenney S.C. X-box-binding protein 1 activates lytic Epstein-Barr virus gene expression in combination with protein kinase D. J Virol 2007, 81:7363-7370.
80. Bhende PM, Kenney SC. Unpublished data. n.d.
81. Buettner M., Lang A., Tudor C.S., Meyer B., Cruchley A., Barros M.H.M., et al. Lytic Epstein-Barr virus infection in epithelial cells but not in B-lymphocytes is dependent on Blimp1. J Gen Virol 2012, 93:1059-1064.
82. Vrzalikova K., Vockerodt M., Leonard S., Bell A., Wei W., Schrader A., et al. Down-regulation of BLIMP1α 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 2011, 117:5907-5917.
83. Jiang R., Gu X., Moore-Medlin T.N., Nathan C.-A., Hutt-Fletcher L.M. Oral dysplasia and squamous cell carcinoma: correlation between increased expression of CD21, Epstein-Barr virus and CK19. Oral Oncol 2012, 48:836-841.
84. Karimi L., Crawford D.H., Speck S., Nicholson L.J. Identification of an epithelial cell differentiation responsive region within the BZLF1 promoter of the Epstein-Barr virus. J Gen Virol 1995, 76(Pt 4):759-765.
85. MacCallum P., Karimi L., Nicholson L.J. Definition of the transcription factors which bind the differentiation responsive element of the Epstein-Barr virus BZLF1 Z promoter in human epithelial cells. J Gen Virol 1999, 80(Pt 6):1501-1512.
86. Bhende P.M., Seaman W.T., Delecluse H.-J., Kenney S.C. The EBV lytic switch protein, Z, preferentially binds to and activates the methylated viral genome. Nat Genet 2004, 36:1099-1104.
87. Bhende P.M., Seaman W.T., Delecluse H.-J., Kenney S.C. BZLF1 activation of the methylated form of the BRLF1 immediate-early promoter is regulated by BZLF1 residue 186. J Virol 2005, 79:7338-7348.
88. Bergbauer M., Kalla M., Schmeinck A., Göbel C., Rothbauer U., Eck S., et al. CpG-methylation regulates a class of Epstein-Barr virus promoters. PLoS Pathog 2010, 6:e1001114.
89. Kalla M., Schmeinck A., Bergbauer M., Pich D., Hammerschmidt W. AP-1 homolog BZLF1 of Epstein-Barr virus has two essential functions dependent on the epigenetic state of the viral genome. Proc Natl Acad Sci 2010, 107:850-855.
90. Ramasubramanyan S., Kanhere A., Osborn K., Flower K., Jenner R.G., Sinclair A.J. Genome-wide analyses of Zta binding to the Epstein-Barr virus genome reveals interactions in both early and late lytic cycles and an epigenetic switch leading to an altered binding profile. J Virol 2012, 86:12494-12502.
91. Yu K.-P., Heston L., Park R., Ding Z., Wang'ondu R., Delecluse H.-J., et al. Latency of Epstein-Barr virus is disrupted by gain-of-function mutant cellular AP-1 proteins that preferentially bind methylated DNA. Proc Natl Acad Sci 2013, 110:8176-8181.
92. Zalani S., Holley-Guthrie E., Kenney S. Epstein-Barr viral latency is disrupted by the immediate-early BRLF1 protein through a cell-specific mechanism. Proc Natl Acad Sci 1996, 93:9194-9199.
93. Meng Q., Hagemeier S.R., Fingeroth J.D., Gershburg E., Pagano J.S., Kenney S.C. The Epstein-Barr virus (EBV)-encoded protein kinase, EBV-PK, but not the thymidine kinase (EBV-TK), is required for ganciclovir and acyclovir inhibition of lytic viral production. J Virol 2010, 84:4534-4542.
94. Fu D.-X., Tanhehco Y., Chen J., Foss C.A., Fox J.J., Chong J.-M., et al. Bortezomib-induced enzyme-targeted radiation therapy in herpesvirus-associated tumors. Nat Med 2008, 14:1118-1122.
95. Westphal E.M., Blackstock W., Feng W., Israel B., Kenney S.C. Activation of lytic Epstein-Barr Virus (EBV) infection by radiation and sodium butyrate in vitro and in vivo: a potential method for treating EBV-positive malignancies. Cancer Res 2000, 60:5781-5788.
96. Feng W., Kenney S.C. Valproic acid enhances the efficacy of chemotherapy in EBV-positive tumors by increasing lytic viral gene expression. Cancer Res 2006, 66:8762-8769.
97. Roychowdhury S., Peng R., Baiocchi R.A., Bhatt D., Vourganti S., Grecula J., et al. Experimental treatment of Epstein-Barr virus-associated primary central nervous system lymphoma. Cancer Res 2003, 63:965-971.
98. Jenkins P.J., Binné U.K., Farrell P.J. Histone acetylation and reactivation of Epstein-Barr virus from latency. J Virol 2000, 74:710-720.
99. Jang E.R., Choi J.D., Park M.A., Jeong G., Cho H., Lee J.-S. ATM modulates transcription in response to histone deacetylase inhibition as part of its DNA damage response. Exp Mol Med 2010, 42:195-204.
100. Daigle D., Gradoville L., Tuck D., Schulz V., Wang'ondu R., Ye J., et al. Valproic acid antagonizes the capacity of other histone deacetylase inhibitors to activate the Epstein-Barr virus lytic cycle. J Virol 2011, 85:5628-5643.
101. Perrine S.P., Hermine O., Small T., Suarez F., O'Reilly R., Boulad F., et al. A phase 1/2 trial of arginine butyrate and ganciclovir in patients with Epstein-Barr virus-associated lymphoid malignancies. Blood 2007, 109:2571-2578.
102. Lane A.A., Chabner B.A. Histone deacetylase inhibitors in cancer therapy. J Clin Oncol 2009, 27:5459-5468.
103. Wildeman M.A., Novalić Z., Verkuijlen S.A.W.M., Juwana H., Huitema A.D.R., Tan I.B., et al. Cytolytic virus activation therapy for Epstein-Barr virus-driven tumors. Clin Cancer Res 2012, 18:5061-5070.
104. Tang W., Harmon P., Gulley M.L., Mwansambo C., Kazembe P.N., Martinson F., et al. Viral response to chemotherapy in endemic Burkitt lymphoma. Clin Cancer Res 2010, 16:2055-2064.