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Novel roles and therapeutic targets of Epstein–Barr virus-encoded latent membrane protein 1-induced oncogenesis in nasopharyngeal carcinoma

Published online by Cambridge University Press:  18 August 2015

Yongguang Tao ,
Ying Shi ,
Jiantao Jia ,
Yiqun Jiang ,
Lifang Yang  and
Ya Cao
Yongguang Tao*
Affiliation:
Cancer Research Institute, Central South University, Changsha, Hunan 410078, China Center for Molecular Imaging, Central South University, Changsha, Changsha, Hunan 410078, China Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Changsha, Hunan 410078, China Key Laboratory of Carcinogenesis, Ministry of Health, Changsha, Hunan 410078, China Collaborative Innovation Center of Molecular Engineering for Theranostics, Changsha, Changsha, Hunan 410078, China
Ying Shi
Affiliation:
Cancer Research Institute, Central South University, Changsha, Hunan 410078, China Center for Molecular Imaging, Central South University, Changsha, Changsha, Hunan 410078, China Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Changsha, Hunan 410078, China Key Laboratory of Carcinogenesis, Ministry of Health, Changsha, Hunan 410078, China
Jiantao Jia
Affiliation:
Cancer Research Institute, Central South University, Changsha, Hunan 410078, China Center for Molecular Imaging, Central South University, Changsha, Changsha, Hunan 410078, China Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Changsha, Hunan 410078, China Key Laboratory of Carcinogenesis, Ministry of Health, Changsha, Hunan 410078, China
Yiqun Jiang
Affiliation:
Cancer Research Institute, Central South University, Changsha, Hunan 410078, China Center for Molecular Imaging, Central South University, Changsha, Changsha, Hunan 410078, China Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Changsha, Hunan 410078, China Key Laboratory of Carcinogenesis, Ministry of Health, Changsha, Hunan 410078, China
Lifang Yang
Affiliation:
Cancer Research Institute, Central South University, Changsha, Hunan 410078, China Center for Molecular Imaging, Central South University, Changsha, Changsha, Hunan 410078, China Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Changsha, Hunan 410078, China Key Laboratory of Carcinogenesis, Ministry of Health, Changsha, Hunan 410078, China Collaborative Innovation Center of Molecular Engineering for Theranostics, Changsha, Changsha, Hunan 410078, China
Ya Cao*
Affiliation:
Cancer Research Institute, Central South University, Changsha, Hunan 410078, China Center for Molecular Imaging, Central South University, Changsha, Changsha, Hunan 410078, China Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Changsha, Hunan 410078, China Key Laboratory of Carcinogenesis, Ministry of Health, Changsha, Hunan 410078, China Collaborative Innovation Center of Molecular Engineering for Theranostics, Changsha, Changsha, Hunan 410078, China
*
*Corresponding authors: Y. Tao, Cancer Research Institute, Central South University, Changsha, Hunan, 410078China. Tel. +(86) 731-84805448; Fax. +(86) 731-84470589 Email: [email protected]Y. Cao, Cancer Research Institute, Central South University, Changsha, Hunan 410078, China Email: [email protected]
*Corresponding authors: Y. Tao, Cancer Research Institute, Central South University, Changsha, Hunan, 410078China. Tel. +(86) 731-84805448; Fax. +(86) 731-84470589 Email: [email protected]Y. Cao, Cancer Research Institute, Central South University, Changsha, Hunan 410078, China Email: [email protected]
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Abstract

Epstein–Barr virus (EBV) was first discovered 50 years ago as an oncogenic gamma-1 herpesvirus and infects more than 90% of the worldwide adult population. Nasopharyngeal carcinoma (NPC) poses a serious health problem in southern China and is one of the most common cancers among the Chinese. There is now strong evidence supporting a role for EBV in the pathogenesis of NPC. Latent membrane protein 1 (LMP1), a primary oncoprotein encoded by EBV, alters several functional and oncogenic properties, including transformation, cell death and survival in epithelial cells in NPC. LMP1 may increase protein modification, such as phosphorylation, and initiate aberrant signalling via derailed activation of host adaptor molecules and transcription factors. Here, we summarise the novel features of different domains of LMP1 and several new LMP1-mediated signalling pathways in NPC. When then focus on the potential roles of LMP1 in cancer stem cells, metabolism reprogramming, epigenetic modifications and therapy strategies in NPC.

Type
Review Article
Information
Expert Reviews in Molecular Medicine , Volume 17 , 2015 , e15
Copyright
Copyright © Cambridge University Press 2015 

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References

1. Zur Hausen, H. (2009) The search for infectious causes of human cancers: where and why. Virology 392, 1-10 Google Scholar
2. de Martel, C. et al. (2012) Global burden of cancers attributable to infections in 2008: a review and synthetic analysis. Lancet Oncology 13, 607-615 Google Scholar
3. Kutok, J.L. and Wang, F. (2006) Spectrum of Epstein-Barr virus-associated diseases. Annual Review of Pathology 1, 375-404 Google Scholar
4. Dolcetti, R. et al. (2013) Interplay among viral antigens, cellular pathways and tumor microenvironment in the pathogenesis of EBV-driven lymphomas. Seminars in Cancer Biology 23, 441-456 CrossRefGoogle ScholarPubMed
5. Mesri, E.A., Feitelson, M.A. and Munger, K. (2014) Human viral oncogenesis: a cancer hallmarks analysis. Cell Host & Microbe 15, 266-282 Google Scholar
6. Brooks, L. et al. (1992) Epstein-Barr virus latent gene transcription in nasopharyngeal carcinoma cells: coexpression of EBNA1, LMP1, and LMP2 transcripts. Journal of Virology 66, 2689-2697 CrossRefGoogle ScholarPubMed
7. Plottel, C.S. and Blaser, M.J. (2011) Microbiome and malignancy. Cell Host & Microbe 10, 324-335 Google Scholar
8. Lieberman, P.M. (2014) Virology. Epstein-Barr virus turns 50. Science 343, 1323-1325 CrossRefGoogle ScholarPubMed
9. Seto, E. et al. (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. Journal of Medical Virology 76, 82-88 CrossRefGoogle ScholarPubMed
10. Lung, R.W. et al. (2009) Modulation of LMP2A expression by a newly identified Epstein-Barr virus-encoded microRNA miR-BART22. Neoplasia 11, 1174-1184 CrossRefGoogle ScholarPubMed
11. Young, L.S. and Rickinson, A.B. (2004) Epstein-Barr virus: 40 years on, nature reviews. Cancer 4, 757-768 Google Scholar
12. Yoshizaki, T. et al. Pathogenic role of Epstein–Barr virus latent membrane protein-1 in the development of nasopharyngeal carcinoma. Cancer Letters 337, 1-7 Google Scholar
13. Dawson, C.W., Port, R.J. and Young, L.S. (2012) The role of the EBV-encoded latent membrane proteins LMP1 and LMP2 in the pathogenesis of nasopharyngeal carcinoma (NPC). Seminars in Cancer Biology 22, 144-153 Google Scholar
14. Pathmanathan, R. et al. (1995) Clonal proliferations of cells infected with Epstein-Barr virus in preinvasive lesions related to nasopharyngeal carcinoma. New England Journal of Medicine 333, 693-698 Google Scholar
15. Ni, C. et al. (2015) In-cell infection: a novel pathway for Epstein–Barr virus infection mediated by cell-in-cell structures. Cell Research 25, 785-800 CrossRefGoogle ScholarPubMed
16. Soni, V. et al. (2006) LMP1 transmembrane domain 1 and 2 (TM1-2) FWLY mediates intermolecular interactions with TM3-6 to activate NF-kappaB. Journal of Virology 80, 10787-10793 Google Scholar
17. Yasui, T. et al. (2004) Latent infection membrane protein transmembrane FWLY is critical for intermolecular interaction, raft localization, and signaling. Proceedings of the National Academy of Sciences of the United States of America 101, 278-283 CrossRefGoogle ScholarPubMed
18. Meckes, D.G. Jr., Menaker, N.F. and Raab-Traub, N. (2013) Epstein-Barr virus LMP1 modulates lipid raft microdomains and the vimentin cytoskeleton for signal transduction and transformation. Journal of Virology 87, 1301-1311 Google Scholar
19. Lingwood, D. and Simons, K. (2010) Lipid rafts as a membrane-organizing principle. Science 327, 46-50 CrossRefGoogle ScholarPubMed
20. Verweij, F.J. et al. (2011) LMP1 association with CD63 in endosomes and secretion via exosomes limits constitutive NF-kappaB activation. EMBO Journal 30, 2115-2129 CrossRefGoogle ScholarPubMed
21. Verweij, F.J., Middeldorp, J.M. and Pegtel, D.M. (2012) Intracellular signaling controlled by the endosomal-exosomal pathway. Communicative & Integrative Biology 5, 88-93 Google Scholar
22. Aga, M. et al. (2014) Exosomal HIF1alpha supports invasive potential of nasopharyngeal carcinoma-associated LMP1-positive exosomes. Oncogene 33, 4613-4622 CrossRefGoogle ScholarPubMed
23. Lee, D.Y. and Sugden, B. (2008) The latent membrane protein 1 oncogene modifies B-cell physiology by regulating autophagy. Oncogene 27, 2833-2842 CrossRefGoogle ScholarPubMed
24. Silva, L.M. and Jung, J.U. (2013) Modulation of the autophagy pathway by human tumor viruses. Seminars in Cancer Biology 23, 323-328 CrossRefGoogle ScholarPubMed
25. Zheng, H. et al. (2007) Role of Epstein-Barr virus encoded latent membrane protein 1 in the carcinogenesis of nasopharyngeal carcinoma. Cellular & Molecular Immunology 4, 185-196 Google Scholar
26. Li, H.P. and Chang, Y.S. (2003) Epstein-Barr virus latent membrane protein 1: structure and functions. Journal of Biomedical Science 10, 490-504 Google Scholar
27. Ndour, P.A. et al. (2012) Inhibition of latent membrane protein 1 impairs the growth and tumorigenesis of latency II Epstein-Barr virus-transformed T cells. Journal of Virology 86, 3934-3943 CrossRefGoogle ScholarPubMed
28. Greenfeld, H. et al. (2015) TRAF1 coordinates polyubiquitin signaling to enhance Epstein-Barr virus LMP1-mediated growth and survival pathway activation. PLoS Pathogens 11, e1004890 Google Scholar
29. Tworkoski, K. and Raab-Traub, N. (2015) LMP1 promotes expression of insulin-like growth factor 1 (IGF1) to selectively activate IGF1 receptor and drive cell proliferation. Journal of Virology 89, 2590-2602 CrossRefGoogle ScholarPubMed
30. Gires, O. et al. (1999) Latent membrane protein 1 of Epstein-Barr virus interacts with JAK3 and activates STAT proteins. EMBO Journal 18, 3064-3073 CrossRefGoogle ScholarPubMed
31. Liu, Y.P. et al. (2008) Phosphorylation and nuclear translocation of STAT3 regulated by the Epstein–Barr virus latent membrane protein 1 in nasopharyngeal carcinoma. International Journal of Molecular Medicine 21, 153-162 Google ScholarPubMed
32. Higuchi, M., Kieff, E. and Izumi, K.M. (2002) The Epstein–Barr virus latent membrane protein 1 putative Janus kinase 3 (JAK3) binding domain does not mediate JAK3 association or activation in B-lymphoma or lymphoblastoid cell lines. Journal of Virology 76, 455-459 Google Scholar
33. Bentz, G.L., Whitehurst, C.B. and Pagano, J.S. (2011) Epstein–Barr virus latent membrane protein 1 (LMP1) C-terminal-activating region 3 contributes to LMP1-mediated cellular migration via its interaction with Ubc9. Journal of Virology 85, 10144-10153 CrossRefGoogle ScholarPubMed
34. Bentz, G.L., Shackelford, J. and Pagano, J.S. (2012) Epstein–Barr virus latent membrane protein 1 regulates the function of interferon regulatory factor 7 by inducing its sumoylation. Journal of Virology 86, 12251-12261 CrossRefGoogle ScholarPubMed
35. Bentz, G.L. et al. (2015) LMP1-induced sumoylation influences the maintenance of EBV latency through KAP1. Journal of Virology 89, 7465-7477 CrossRefGoogle ScholarPubMed
36. Vanden Berghe, T. et al. (2014) Regulated necrosis: the expanding network of non-apoptotic cell death pathways, nature reviews. Molecular Cell Biology 15, 135-147 Google Scholar
37. Liu, Y. et al. (2002) Latent membrane protein-1 of Epstein–Barr virus inhibits cell growth and induces sensitivity to cisplatin in nasopharyngeal carcinoma cells. Journal of Medical Virology 66, 63-69 CrossRefGoogle ScholarPubMed
38. Zhang, X. et al. (2002) Apoptosis modulation of Epstein–Barr virus-encoded latent membrane protein 1 in the epithelial cell line HeLa is stimulus-dependent. Virology 304, 330-341 CrossRefGoogle ScholarPubMed
39. Faqing, T. et al. (2005) Epstein–Barr virus LMP1 initiates cell proliferation and apoptosis inhibition via regulating expression of survivin in nasopharyngeal carcinoma. Experimental Oncology 27, 96-101 Google Scholar
40. Liu, M.T. et al. (2004) Epstein–Barr virus latent membrane protein 1 induces micronucleus formation, represses DNA repair and enhances sensitivity to DNA-damaging agents in human epithelial cells. Oncogene 23, 2531-2539 Google Scholar
41. Dirmeier, U. et al. (2005) Latent membrane protein 1 of Epstein–Barr virus coordinately regulates proliferation with control of apoptosis. Oncogene 24, 1711-1717 CrossRefGoogle ScholarPubMed
42. Brocqueville, G. et al. (2013) LMP1-induced cell death may contribute to the emergency of its oncogenic property. PloS One 8, e60743 CrossRefGoogle Scholar
43. Pratt, Z.L., Zhang, J. and Sugden, B. (2012) The latent membrane protein 1 (LMP1) oncogene of Epstein–Barr virus can simultaneously induce and inhibit apoptosis in B cells. Journal of Virology 86, 4380-4393 Google Scholar
44. Khabir, A. et al. (2005) EBV latent membrane protein 1 abundance correlates with patient age but not with metastatic behavior in North African nasopharyngeal carcinomas. Virology Journal 2, 39 CrossRefGoogle Scholar
45. Wang, Z. et al. (2010) STAT3 activation induced by Epstein-Barr virus latent membrane protein1 causes vascular endothelial growth factor expression and cellular invasiveness via JAK3 And ERK signaling. European Journal of Cancer 46, 2996-3006 CrossRefGoogle ScholarPubMed
46. Chen, C.C. et al. (2014) NF-kappaB-mediated transcriptional upregulation of TNFAIP2 by the Epstein-Barr virus oncoprotein, LMP1, promotes cell motility in nasopharyngeal carcinoma. Oncogene 33, 3648-3659 Google Scholar
47. Fang, W. et al. (2014) EBV-driven LMP1 and IFN-gamma up-regulate PD-L1 in nasopharyngeal carcinoma: Implications for oncotargeted therapy. Oncotarget 5, 12189-12202 Google Scholar
48. Li, T. et al. (2012) Tumor suppression in the absence of p53-mediated cell-cycle arrest, apoptosis, and senescence. Cell 149, 1269-1283 CrossRefGoogle ScholarPubMed
49. Lujambio, A. et al. (2013) Non-cell-autonomous tumor suppression by p53. Cell 153, 449-460 Google Scholar
50. Spruck, C.H. 3rd et al. (1992) Absence of p53 gene mutations in primary nasopharyngeal carcinomas. Cancer Research 52, 4787-4790 Google Scholar
51. Sun, Y. et al. (1992) An infrequent point mutation of the p53 gene in human nasopharyngeal carcinoma. Proceedings of the National Academy of Sciences of the United States of America 89, 6516-6520 Google Scholar
52. Li, L. et al. (2007) Latent membrane protein 1 of Epstein-Barr virus regulates p53 phosphorylation through MAP kinases. Cancer Letters 255, 219-231 Google Scholar
53. Saridakis, V. et al. (2005) Structure of the p53 binding domain of HAUSP/USP7 bound to Epstein-Barr nuclear antigen 1 implications for EBV-mediated immortalization. Molecular Cell 18, 25-36 Google Scholar
54. Sivachandran, N., Sarkari, F. and Frappier, L. (2008) Epstein-Barr nuclear antigen 1 contributes to nasopharyngeal carcinoma through disruption of PML nuclear bodies. PLoS Pathogens 4, e1000170 Google Scholar
55. Li, L. et al. (2007) Ubiquitination of MDM2 modulated by Epstein-Barr virus encoded latent membrane protein 1. Virus Research 130, 275-280 CrossRefGoogle ScholarPubMed
56. Li, L. et al. (2012) Viral oncoprotein LMP1 disrupts p53-induced cell cycle arrest and apoptosis through modulating K63-linked ubiquitination of p53. Cell Cycle 11, 2327-2336 Google Scholar
57. Guo, L. et al. (2012) Epstein-Barr virus oncoprotein LMP1 mediates survivin upregulation by p53 contributing to G1/S cell cycle progression in nasopharyngeal carcinoma. International Journal of Molecular Medicine 29, 574-580 Google Scholar
58. Dittmann, K. et al. (2008) Radiation-induced caveolin-1 associated EGFR internalization is linked with nuclear EGFR transport and activation of DNA-PK. Molecular Cancer 7, 69 Google Scholar
59. Wang, S.C. et al. (2006) Tyrosine phosphorylation controls PCNA function through protein stability. Nature Cell Biology 8, 1359-1368 Google Scholar
60. Linggi, B. and Carpenter, G. (2006) ErbB receptors: new insights on mechanisms and biology. Trends in Cell Biology 16, 649-656 Google Scholar
61. Kim, J. et al. (2007) The phosphoinositide kinase PIKfyve mediates epidermal growth factor receptor trafficking to the nucleus. Cancer Research 67, 9229-9237 CrossRefGoogle ScholarPubMed
62. Wanner, G. et al. (2008) Activation of protein kinase Cepsilon stimulates DNA-repair via epidermal growth factor receptor nuclear accumulation. Radiotherapy & Oncology 86, 383-390 Google Scholar
63. Li, C. et al. (2009) Nuclear EGFR contributes to acquired resistance to cetuximab. Oncogene 28, 3801-3813 CrossRefGoogle ScholarPubMed
64. Tao, Y. et al. (2005) Nuclear accumulation of epidermal growth factor receptor and acceleration of G1/S stage by Epstein-Barr-encoded oncoprotein latent membrane protein 1. Experimental Cell Research, 303, 240-251 Google Scholar
65. Wang, Y.N. et al. (2010) Nuclear trafficking of the epidermal growth factor receptor family membrane proteins. Oncogene 29, 3997-4006 CrossRefGoogle ScholarPubMed
66. Brand, T.M. et al. (2013) Nuclear EGFR as a molecular target in cancer. Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology 108, 370-377 Google Scholar
67. Shi, Y. et al. (2012) Nuclear epidermal growth factor receptor interacts with transcriptional intermediary factor 2 to activate cyclin D1 gene expression triggered by the oncoprotein latent membrane protein 1. Carcinogenesis 33, 1468-1478 Google Scholar
68. Santarius, T. et al. (2010) A census of amplified and overexpressed human cancer genes. Nature Reviews Cancer 10, 59-64 Google Scholar
69. Lo, H.W. et al. (2005) Nuclear interaction of EGFR and STAT3 in the activation of the iNOS/NO pathway. Cancer Cell 7, 575-589 Google Scholar
70. Hsiao, J.R. et al. (2003) Constitutive activation of STAT3 and STAT5 is present in the majority of nasopharyngeal carcinoma and correlates with better prognosis. British Journal of Cancer 89, 344-349 Google Scholar
71. Ting, C.M. et al. (2012) Role of STAT3/5 and Bcl-2/xL in 2-methoxyestradiol-induced endoreduplication of nasopharyngeal carcinoma cells. Molecular Carcinogenesis 51, 963-972 Google Scholar
72. Xu, Y. et al. (2013) Epstein-Barr Virus encoded LMP1 regulates cyclin D1 promoter activity by nuclear EGFR and STAT3 in CNE1 cells. Journal of Experimental & Clinical Cancer Research 32, 90 Google Scholar
73. Yan, G. et al. (2006) Identification of novel phosphoproteins in signaling pathways triggered by latent membrane protein 1 using functional proteomics technology. Proteomics 6, 1810-1821 Google Scholar
74. Curmi, P.A. et al. (2000) Overexpression of stathmin in breast carcinomas points out to highly proliferative tumours. British Journal of Cancer 82, 142-150 Google Scholar
75. Mistry, S.J. and Atweh, G.F. (2002) Role of stathmin in the regulation of the mitotic spindle: potential applications in cancer therapy. Mount Sinai Journal of Medicine 69, 299-304 Google ScholarPubMed
76. Lin, X. et al. (2009) EBV-encoded LMP1 regulates Op18/stathmin signaling pathway by cdc2 mediation in nasopharyngeal carcinoma cells. International Journal of Cancer (Journal International du Cancer) 124, 1020-1027 Google Scholar
77. Belletti, B. et al. (2008) Stathmin activity influences sarcoma cell shape, motility, and metastatic potential. Molecular Biology of the Cell 19, 2003-2013 CrossRefGoogle ScholarPubMed
78. Cheng, A.L. et al. (2008) Identification of novel nasopharyngeal carcinoma biomarkers by laser capture microdissection and proteomic analysis. Clinical Cancer Research 14, 435-445 Google Scholar
79. Wu, Y. et al. (2014) A combination of paclitaxel and siRNA-mediated silencing of Stathmin inhibits growth and promotes apoptosis of nasopharyngeal carcinoma cells. Cell Oncology (Dordr), 37, 53-67 Google Scholar
80. Lin, X. et al. (2012) Epstein-Barr virus-encoded LMP1 triggers regulation of the ERK-mediated Op18/stathmin signaling pathway in association with cell cycle. Cancer Science 103, 993-999 Google Scholar
81. Endo, K. et al. (2009) Phosphorylated ezrin is associated with EBV latent membrane protein 1 in nasopharyngeal carcinoma and induces cell migration. Oncogene 28, 1725-1735 Google Scholar
82. Yan, G. et al. (2007) Epstein-Barr virus latent membrane protein 1 mediates phosphorylation and nuclear translocation of annexin A2 by activating PKC pathway. Cellular Signalling 19, 341-348 Google Scholar
83. Luo, W. et al. (2008) Epstein-Barr virus latent membrane protein 1 mediates serine 25 phosphorylation and nuclear entry of annexin A2 via PI-PLC-PKCalpha/PKCbeta pathway. Molecular Carcinogenesis 47, 934-946 Google Scholar
84. Muller, A. et al. (2001) Involvement of chemokine receptors in breast cancer metastasis. Nature 410, 50-56 Google Scholar
85. Kucia, M. et al. (2004) CXCR4-SDF-1 signalling, locomotion, chemotaxis and adhesion. Journal of Molecular Histology 35, 233-245 Google Scholar
86. Kucia, M. et al. (2005) Trafficking of normal stem cells and metastasis of cancer stem cells involve similar mechanisms: pivotal role of the SDF-1-CXCR4 axis. Stem Cells 23, 879-894 Google Scholar
87. Hu, J. et al. (2005) The expression of functional chemokine receptor CXCR4 is associated with the metastatic potential of human nasopharyngeal carcinoma. Clinical Cancer Research 11, 4658-4665 CrossRefGoogle ScholarPubMed
88. Kondo, S. et al. (2006) EBV latent membrane protein 1 up-regulates hypoxia-inducible factor 1alpha through Siah1-mediated down-regulation of prolyl hydroxylases 1 and 3 in nasopharyngeal epithelial cells. Cancer Research 66, 9870-9877 Google Scholar
89. Luftig, M. et al. (2004) Epstein-Barr virus latent infection membrane protein 1 TRAF-binding site induces NIK/IKK alpha-dependent noncanonical NF-kappaB activation. Proceedings of the National Academy of Sciences of the United States of America 101, 141-146 CrossRefGoogle ScholarPubMed
90. Nakayama, T. et al. (2002) Human B cells immortalized with Epstein-Barr virus upregulate CCR6 and CCR10 and downregulate CXCR4 and CXCR5. Journal of Virology 76, 3072-3077 Google Scholar
91. Li, J. et al. (2007) Expression of immune-related molecules in primary EBV-positive Chinese nasopharyngeal carcinoma: associated with latent membrane protein 1 (LMP1) expression. Cancer Biology & Therapy 6, 1997-2004 Google Scholar
92. Farzan, M. et al. (1999) Tyrosine sulfation of the amino terminus of CCR5 facilitates HIV-1 entry. Cell 96, 667-676 Google Scholar
93. Farzan, M. et al. (2002) The role of post-translational modifications of the CXCR4 amino terminus in stromal-derived factor 1 alpha association and HIV-1 entry. Journal of Biological Chemistry 277, 29484-29489 Google Scholar
94. Seibert, C. et al. (2002) Tyrosine sulfation of CCR5 N-terminal peptide by tyrosylprotein sulfotransferases 1 and 2 follows a discrete pattern and temporal sequence. Proceedings of the National Academy of Sciences of the United States of America 99, 11031-11036 Google Scholar
95. Xu, C. et al. (2007) Human anti-CXCR4 antibodies undergo VH replacement, exhibit functional V-region sulfation, and define CXCR4 antigenic heterogeneity. Journal of Immunology 179, 2408-2418 Google Scholar
96. Liu, J. et al. (2008) Tyrosine sulfation is prevalent in human chemokine receptors important in lung disease. American Journal of Respiratory Cell and Molecular Biology 38, 738-743 CrossRefGoogle ScholarPubMed
97. Seibert, C. et al. (2008) Sequential tyrosine sulfation of CXCR4 by tyrosylprotein sulfotransferases. Biochemistry 47, 11251-11262 Google Scholar
98. Beisswanger, R. et al. (1998) Existence of distinct tyrosylprotein sulfotransferase genes: molecular characterization of tyrosylprotein sulfotransferase-2. Proceedings of the National Academy of Sciences of the United States of America 95, 11134-11139 Google Scholar
99. Moore, K.L. (2009) Protein tyrosine sulfation: a critical posttranslation modification in plants and animals. Proceedings of the National Academy of Sciences of the United States of America 106, 14741-14742 Google Scholar
100. Xu, J. et al. (2013) Tyrosylprotein sulfotransferase-1 and tyrosine sulfation of chemokine receptor 4 are induced by Epstein-Barr virus encoded latent membrane protein 1 and associated with the metastatic potential of human nasopharyngeal carcinoma. PLoS ONE 8, e56114 Google Scholar
101. Chen, Z., Qiu, X. and Gu, J. (2009) Immunoglobulin expression in non-lymphoid lineage and neoplastic cells. American Journal of Pathology 174, 1139-1148 Google Scholar
102. Geng, L.Y. et al. (2007) Expression of SNC73, a transcript of the immunoglobulin alpha-1 gene, in human epithelial carcinomas. World Journal of Gastroenterology 13, 2305-2311 Google Scholar
103. Hu, D. et al. (2011) Heterogeneity of aberrant immunoglobulin expression in cancer cells. Cellular & Molecular Immunology 8, 479-485 Google Scholar
104. Hu, D. et al. (2008) Immunoglobulin expression and its biological significance in cancer cells. Cellular & Molecular Immunology 5, 319-324 Google Scholar
105. Li, M. et al. (2004) Expression of immunoglobulin kappa light chain constant region in abnormal human cervical epithelial cells. International Journal of Biochemistry & Cell Biology 36, 2250-2257 Google Scholar
106. Li, M. et al. (2001) Nucleotide sequence analysis of a transforming gene isolated from nasopharyngeal carcinoma cell line CNE2: an aberrant human immunoglobulin kappa light chain which lacks variable region. DNA Sequence: The Journal of DNA Sequencing and Mapping 12, 331-335 CrossRefGoogle ScholarPubMed
107. Li, L. et al. (2012) Methylation profiling of Epstein-Barr virus immediate-early gene promoters, BZLF1 and BRLF1 in tumors of epithelial, NK- and B-cell origins. BMC Cancer 12, 125 CrossRefGoogle ScholarPubMed
108. Qiu, X. et al. (2003) Human epithelial cancers secrete immunoglobulin g with unidentified specificity to promote growth and survival of tumor cells. Cancer Research 63, 6488-6495 Google Scholar
109. Zheng, H. et al. (2007) Immunoglobulin alpha heavy chain derived from human epithelial cancer cells promotes the access of S phase and growth of cancer cells. Cell Biology International 31, 82-87 Google Scholar
110. Zheng, H. et al. (2007) Expression and secretion of immunoglobulin alpha heavy chain with diverse VDJ recombinations by human epithelial cancer cells. Molecular Immunology 44, 2221-2227 Google Scholar
111. Bergman, Y. et al. (1984) Two regulatory elements for immunoglobulin kappa light chain gene expression. Proceedings of the National Academy of Sciences of the United States of America 81, 7041-7045 Google Scholar
112. Meyer, K.B. and Neuberger, M.S. (1989) The immunoglobulin kappa locus contains a second, stronger B-cell-specific enhancer which is located downstream of the constant region. EMBO Journal 8, 1959-1964 Google Scholar
113. Judde, J.G. and Max, E.E. (1992) Characterization of the human immunoglobulin kappa gene 3 enhancer: functional importance of three motifs that demonstrate B-cell-specific in vivo footprints. Molecular and Cellular Biology 12, 5206-5216 Google Scholar
114. Liao, W. et al. (1999) Epstein-Barr virus encoded latent membrane protein 1 increases expression of immunoglobulin kappa light chain through NFkappaB in a nasopharyngeal carcinoma cell line. Sheng wu hua xue yu sheng wu wu li xue bao Acta Biochimica et Biophysica Sinica 31, 659-663 Google Scholar
115. Liu, H. et al. (2009) LMP1-augmented kappa intron enhancer activity contributes to upregulation expression of Ig kappa light chain via NF-kappaB and AP-1 pathways in nasopharyngeal carcinoma cells. Molecular Cancer 8, 92 Google Scholar
116. Liu, H. et al. (2012) EBV-encoded LMP1 upregulates Igkappa 3 enhancer activity and Igkappa expression in nasopharyngeal cancer cells by activating the Ets-1 through ERKs signaling. PLoS ONE 7, e32624 Google Scholar
117. Duan, Z. et al. (2014) Activation of the Ig Ialpha1 promoter by the transcription factor Ets-1 triggers Ig Ialpha1-Calpha1 germline transcription in epithelial cancer cells. Cellular & Molecular Immunology 11, 197-205 Google Scholar
118. Li, J. et al. (2007) Functional inactivation of EBV-specific T-lymphocytes in nasopharyngeal carcinoma: implications for tumor immunotherapy. PLoS ONE 2, e1122 Google Scholar
119. Middeldorp, J.M. and Pegtel, D.M. (2008) Multiple roles of LMP1 in Epstein-Barr virus induced immune escape. Seminars in Cancer Biology 18, 388-396 Google Scholar
120. Dukers, D.F. et al. (2000) Direct immunosuppressive effects of EBV-encoded latent membrane protein 1. Journal of Immunology 165, 663-670 Google Scholar
121. Flanagan, J., Middeldorp, J. and Sculley, T. (2003) Localization of the Epstein-Barr virus protein LMP 1 to exosomes. Journal of General Virology 84, 1871-1879 Google Scholar
122. Keryer-Bibens, C. et al. (2006) Exosomes released by EBV-infected nasopharyngeal carcinoma cells convey the viral latent membrane protein 1 and the immunomodulatory protein galectin 9. BMC Cancer 6, 283 Google Scholar
123. Pai, S. et al. (2007) Nasopharyngeal carcinoma-associated Epstein-Barr virus-encoded oncogene latent membrane protein 1 potentiates regulatory T-cell function. Immunology and Cell Biology 85, 370-377 Google Scholar
124. Kondo, S. et al. (2011) Epstein-Barr virus latent membrane protein 1 induces cancer stem/progenitor-like cells in nasopharyngeal epithelial cell lines. Journal of Virology 85, 11255-11264 Google Scholar
125. Yang, C.F. et al. (2014) Cancer stem-like cell characteristics induced by EB virus-encoded LMP1 contribute to radioresistance in nasopharyngeal carcinoma by suppressing the p53-mediated apoptosis pathway. Cancer Letters 344, 260-271 Google Scholar
126. Lun, S.W. et al. (2012) CD44+ cancer stem-like cells in EBV-associated nasopharyngeal carcinoma. PLoS ONE 7, e52426 Google Scholar
127. Port, R.J. et al. (2013) Epstein-Barr virus induction of the Hedgehog signalling pathway imposes a stem cell phenotype on human epithelial cells. Journal of Pathology 231, 367-377 Google Scholar
128. Wasil, L.R. et al. (2015) Regulation of DNA damage signaling and cell death responses by Epstein-Barr virus Latent Membrane Proteins (LMP) 1 and LMP2A in nasopharyngeal carcinoma cells. Journal of Virology 89, 7612-7624 Google Scholar
129. Vander Heiden, M.G., Cantley, L.C. and Thompson, C.B. (2009) Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science 324, 1029-1033 Google Scholar
130. Zwerschke, W. et al. (1999) Modulation of type M2 pyruvate kinase activity by the human papillomavirus type 16 E7 oncoprotein. Proceedings of the National Academy of Sciences of the United States of America 96, 1291-1296 Google Scholar
131. Munger, J. et al. (2006) Dynamics of the cellular metabolome during human cytomegalovirus infection. PLoS Pathogens 2, e132 Google Scholar
132. Delgado, T. et al. (2010) Induction of the Warburg effect by Kaposi's sarcoma herpesvirus is required for the maintenance of latently infected endothelial cells. Proceedings of the National Academy of Sciences of the United States of America 107, 10696-10701 Google Scholar
133. Diamond, D.L. et al. (2010) Temporal proteome and lipidome profiles reveal hepatitis C virus-associated reprogramming of hepatocellular metabolism and bioenergetics. PLoS Pathogens 6, e1000719 Google Scholar
134. Xiao, L. et al. (2014) Targeting Epstein–Barr virus oncoprotein LMP1-mediated glycolysis sensitizes nasopharyngeal carcinoma to radiation therapy. Oncogene 33, 4568-4578 Google Scholar
135. Mathupala, S.P., Ko, Y.H. and Pedersen, P.L. (2009) Hexokinase-2 bound to mitochondria: cancer's stygian link to the ‘Warburg effect’ and a pivotal target for effective therapy. Seminars in Cancer Biology 19, 17-24 Google Scholar
136. Lo, A.K. et al. (2015) Activation of the FGFR1 signalling pathway by the Epstein-Barr Virus-encoded LMP1 promotes aerobic glycolysis and transformation of human nasopharyngeal epithelial cells. Journal of Pathology. doi: 10.1002/path.4575 Google Scholar
137. Su, M.A. et al. (2014) An invertebrate Warburg effect: a shrimp virus achieves successful replication by altering the host Metabolome via the PI3K-Akt-mTOR pathway. PLoS Pathogens 10, e1004196 Google Scholar
138. Darekar, S. et al. (2012) Epstein-Barr virus immortalization of human B-cells leads to stabilization of hypoxia-induced factor 1 alpha, congruent with the Warburg effect. PLoS ONE 7, e42072 Google Scholar
139. Fernandez, A.F. et al. (2009) The dynamic DNA methylomes of double-stranded DNA viruses associated with human cancer. Genome Research 19, 438-451 Google Scholar
140. Tong, J.H. et al. (2002) Quantitative Epstein-Barr virus DNA analysis and detection of gene promoter hypermethylation in nasopharyngeal (NP) brushing samples from patients with NP carcinoma. Clinical Cancer Research 8, 2612-2619 Google Scholar
141. Yi, B. et al. (2009) Inactivation of 14-3-3 sigma by promoter methylation correlates with metastasis in nasopharyngeal carcinoma. Journal of Cellular Biochemistry 106, 858-866 Google Scholar
142. Yanatatsaneejit, P. et al. (2008) Promoter hypermethylation of CCNA1, RARRES1, and HRASLS3 in nasopharyngeal carcinoma. Oral Oncology 44, 400-406 Google Scholar
143. Liu, H. et al. (2008) Promoter methylation inhibits BRD7 expression in human nasopharyngeal carcinoma cells. BMC Cancer 8, 253 Google Scholar
144. Lee, K.Y. et al. (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 Google Scholar
145. Cui, Y. et al. (2008) OPCML is a broad tumor suppressor for multiple carcinomas and lymphomas with frequently epigenetic inactivation. PLoS ONE 3, e2990 Google Scholar
146. Zhang, Z. et al. (2007) Inactivation of RASSF2A by promoter methylation correlates with lymph node metastasis in nasopharyngeal carcinoma. International Journal of Cancer 120, 32-38 Google Scholar
147. Shao, L. et al. (2007) CMTM5 exhibits tumor suppressor activities and is frequently silenced by methylation in carcinoma cell lines. Clinical Cancer Research 13, 5756-5762 Google Scholar
148. Chow, L.S. et al. (2004) RASSF1A is a target tumor suppressor from 3p21.3 in nasopharyngeal carcinoma. International Journal of Cancer 109, 839-847 Google Scholar
149. Tao, Q. and Chan, A.T. (2007) Nasopharyngeal carcinoma: molecular pathogenesis and therapeutic developments. Expert Reviews in Molecular Medicine 9, 1-24 CrossRefGoogle ScholarPubMed
150. Hino, R. et al. (2009) Activation of DNA methyltransferase 1 by EBV latent membrane protein 2A leads to promoter hypermethylation of PTEN gene in gastric carcinoma. Cancer Research 69, 2766-2774 Google Scholar
151. Niemhom, S. et al. (2008) Hypermethylation of epithelial-cadherin gene promoter is associated with Epstein-Barr virus in nasopharyngeal carcinoma. Cancer Detection and Prevention 32, 127-134 Google Scholar
152. Zhou, L. et al. (2005) Frequent hypermethylation of RASSF1A and TSLC1, and high viral load of Epstein-Barr Virus DNA in nasopharyngeal carcinoma and matched tumor-adjacent tissues. Neoplasia 7, 809-815 Google Scholar
153. Tsai, C.N. et al. (2002) The Epstein-Barr virus oncogene product, latent membrane protein 1, induces the downregulation of E-cadherin gene expression via activation of DNA methyltransferases. Proceedings of the National Academy of Sciences of the United States of America 99, 10084-10089 Google Scholar
154. Tsai, C.L. et al. (2006) Activation of DNA methyltransferase 1 by EBV LMP1 involves c-Jun NH(2)-terminal kinase signaling. Cancer Research 66, 11668-11676 Google Scholar
155. Seo, S.Y., Kim, E.O. and Jang, K.L. (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 Letters 270, 66-76 Google Scholar
156. Horikawa, T. et al. (2007) Twist and epithelial-mesenchymal transition are induced by the EBV oncoprotein latent membrane protein 1 and are associated with metastatic nasopharyngeal carcinoma. Cancer Research 67, 1970-1978 Google Scholar
157. Sides, M.D. et al. (2011) The Epstein-Barr virus latent membrane protein 1 and transforming growth factor--beta1 synergistically induce epithelial--mesenchymal transition in lung epithelial cells. American Journal of Respiratory Cell and Molecular Biology 44, 852-862 CrossRefGoogle ScholarPubMed
158. Horikawa, T. et al. (2011) Epstein-Barr Virus latent membrane protein 1 induces snail and epithelial-mesenchymal transition in metastatic nasopharyngeal carcinoma. British Journal of Cancer 104, 1160-1167 Google Scholar
159. Luo, W. and Yao, K. (2013) Molecular characterization and clinical implications of spindle cells in nasopharyngeal carcinoma: a novel molecule-morphology model of tumor progression proposed. PLoS ONE 8, e83135 CrossRefGoogle ScholarPubMed
160. Li, R. et al. (2014) Fisetin inhibits migration, invasion and epithelial-mesenchymal transition of LMP1-positive nasopharyngeal carcinoma cells. Molecular Medicine Reports 9, 413-418 Google Scholar
161. Jiang, Y. et al. (2015) Repression of Hox genes by LMP1 in nasopharyngeal carcinoma and modulation of glycolytic pathway genes by HoxC8. Oncogene. doi: 10.1038/onc.2015.53 Google Scholar
162. Schiller, J.T. and Davies, P. (2004) Delivering on the promise: HPV vaccines and cervical cancer, Nature reviews. Microbiology 2, 343-347 Google Scholar
163. Epstein, M.A. et al. (1985) Protection of cottontop tamarins against Epstein-Barr virus-induced malignant lymphoma by a prototype subunit vaccine. Nature 318, 287-289 Google Scholar
164. Sokal, E.M. et al. (2007) Recombinant gp350 vaccine for infectious mononucleosis: a phase 2, randomized, double-blind, placebo-controlled trial to evaluate the safety, immunogenicity, and efficacy of an Epstein-Barr virus vaccine in healthy young adults. Journal of Infectious Diseases 196, 1749-1753 Google Scholar
165. Cohen, J.I. et al. (2013) The need and challenges for development of an Epstein-Barr virus vaccine. Vaccine 31, (Suppl 2), B194-B196 Google Scholar
166. Balfour, H.H. Jr. (2014) Progress, prospects, and problems in Epstein–Barr virus vaccine development. Current Opinion in Virology 6C, 1-5 CrossRefGoogle Scholar
167. Hui, E.P. et al. (2013) Phase I trial of recombinant modified vaccinia ankara encoding Epstein-Barr viral tumor antigens in nasopharyngeal carcinoma patients. Cancer Research 73, 1676-1688 Google Scholar
168. Fang, C.Y. et al. (2007) Modulation of Epstein-Barr virus latent membrane protein 1 activity by intrabodies. Intervirology 50, 254-263 Google Scholar
169. Delbende, C. et al. (2009) Induction of therapeutic antibodies by vaccination against external loops of tumor-associated viral latent membrane protein. Journal of Virology 83, 11734-11745 Google Scholar
170. Paramita, D.K. et al. (2011) Humoral immune responses to Epstein-Barr virus encoded tumor associated proteins and their putative extracellular domains in nasopharyngeal carcinoma patients and regional controls. Journal of Medical Virology 83, 665-678 Google Scholar
171. Chen, R. et al. (2012) A human fab-based immunoconjugate specific for the LMP1 extracellular domain inhibits nasopharyngeal carcinoma growth in vitro and in vivo. Molecular Cancer Therapeutics 11, 594-603 Google Scholar
172. Gennari, F. et al. (2004) Direct phage to intrabody screening (DPIS): demonstration by isolation of cytosolic intrabodies against the TES1 site of Epstein Barr virus latent membrane protein 1 (LMP1) that block NF-kappaB transactivation. Journal of Molecular Biology 335, 193-207 Google Scholar
173. Mei, Y.P. et al. (2006) siRNA targeting LMP1-induced apoptosis in EBV-positive lymphoma cells is associated with inhibition of telomerase activity and expression. Cancer Letters 232, 189-198 CrossRefGoogle ScholarPubMed
174. Mei, Y.P. et al. (2007) Silencing of LMP1 induces cell cycle arrest and enhances chemosensitivity through inhibition of AKT signaling pathway in EBV-positive nasopharyngeal carcinoma cells. Cell Cycle 6, 1379-1385 Google Scholar
175. Bollard, C.M. et al. (2004) The generation and characterization of LMP2-specific CTLs for use as adoptive transfer from patients with relapsed EBV-positive Hodgkin disease. Journal of Immunotherapy 27, 317-327 Google Scholar
176. Bollard, C.M. et al. (2014) Sustained complete responses in patients with lymphoma receiving autologous cytotoxic T lymphocytes targeting Epstein–Barr virus latent membrane proteins. Journal of Clinical Oncology 32, 798-808 Google Scholar
177. Cho, S.G. et al. (2015) Long-term outcome of extranodal NK/T Cell lymphoma patients treated with postremission therapy using EBV LMP1 and LMP2a-specific CTLs. Molecular Therapy 23, 1401-1409 Google Scholar
178. Ma, S.D. et al. (2015) LMP1-deficient Epstein-Barr virus mutant requires T cells for lymphomagenesis. Journal of Clinical Investigation 125, 304-315 Google Scholar
179. Tang, X. et al. (2014) T cells expressing a LMP1-specific chimeric antigen receptor mediate antitumor effects against LMP1-positive nasopharyngeal carcinoma cells in vitro and in vivo. Journal of Biomedical Research 28, 468-475 Google Scholar
180. Smith, C. et al. (2012) Effective treatment of metastatic forms of Epstein-Barr virus-associated nasopharyngeal carcinoma with a novel adenovirus-based adoptive immunotherapy. Cancer Research 72, 1116-1125 Google Scholar
181. Lu, Z.X. et al. (2008) DNAzymes targeted to EBV-encoded latent membrane protein-1 induce apoptosis and enhance radiosensitivity in nasopharyngeal carcinoma. Cancer Letters 265, 226-238 Google Scholar
182. Lu, Z.X. et al. (2005) Effect of EBV LMP1 targeted DNAzymes on cell proliferation and apoptosis. Cancer Gene Therapy 12, 647-654 Google Scholar
183. Yang, L. et al. (2010) A therapeutic approach to nasopharyngeal carcinomas by DNAzymes targeting EBV LMP-1 gene. Molecules 15, 6127-6139 Google Scholar
184. Yang, L. et al. (2009) Effect of DNAzymes targeting Akt1 on cell proliferation and apoptosis in nasopharyngeal carcinoma. Cancer Biology & Therapy 8, 366-371 Google Scholar
185. Yang, L. et al. (2015) EBV-LMP1 targeted DNAzyme enhances radiosensitivity by inhibiting tumor angiogenesis via the JNKs/HIF-1 pathway in nasopharyngeal carcinoma. Oncotarget 6, 5804-5817 Google Scholar
186. Ma, X. et al. (2011) Down-regulation of EBV-LMP1 radio-sensitizes nasal pharyngeal carcinoma cells via NF-kappaB regulated ATM expression. PLoS ONE 6, e24647 Google Scholar
187. Chen, Y. et al. (2013) Delivery system for DNAzymes using arginine-modified hydroxyapatite nanoparticles for therapeutic application in a nasopharyngeal carcinoma model. International Journal of Nanomedicine 8, 3107-3118 Google Scholar
188. Ma, X. et al. (2013) EBV-LMP1-targeted DNAzyme induces DNA damage and causes cell cycle arrest in LMP1-positive nasopharyngeal carcinoma cells. International Journal of Oncology 43, 1541-1548 Google Scholar
189. Cao, Y. et al. (2014) Therapeutic evaluation of Epstein-Barr virus-encoded latent membrane protein-1 targeted DNAzyme for treating of nasopharyngeal carcinomas. Molecular Therapy 22, 371-377 Google Scholar
190. Yang, L. et al. (2014) Targeting EBV-LMP1 DNAzyme enhances radiosensitivity of nasopharyngeal carcinoma cells by inhibiting telomerase activity. Cancer Biology & Therapy 15, 61-68 Google Scholar
191. Ding, L. et al. (2005) Epstein-Barr virus encoded latent membrane protein 1 modulates nuclear translocation of telomerase reverse transcriptase protein by activating nuclear factor-kappaB p65 in human nasopharyngeal carcinoma cells. International Journal of Biochemistry & Cell Biology 37, 1881-1889 Google Scholar
192. Yang, J. et al. (2004) Telomerase activation by Epstein-Barr virus latent membrane protein 1 is associated with c-Myc expression in human nasopharyngeal epithelial cells. Journal of Experimental & Clinical Cancer Research 23, 495-506 Google Scholar
193. Ding, L. et al. (2007) Latent membrane protein 1 encoded by Epstein-Barr virus induces telomerase activity via p16INK4A/Rb/E2F1 and JNK signaling pathways. Journal of Medical Virology 79, 1153-1163 Google Scholar
194. Yan, Z. et al. (2004) Interference effect of epigallocatechin-3-gallate on targets of nuclear factor kappaB signal transduction pathways activated by EB virus encoded latent membrane protein 1. International Journal of Biochemistry & Cell Biology 36, 1473-1481 Google Scholar
195. Lee, M. et al. (2015) Quercetin-induced apoptosis prevents EBV infection. Oncotarget 6, 12603-12624 Google Scholar
196. Bei, J.X. et al. (2010) A genome-wide association study of nasopharyngeal carcinoma identifies three new susceptibility loci. Nature Genetics 42, 599-603 Google Scholar
197. Lee, N. et al. (2015) EBV noncoding RNA binds nascent RNA to drive host PAX5 to viral DNA. Cell 160, 607-618 Google Scholar
198. Xiong, G. et al. (2014) Epstein-Barr Virus (EBV) infection in Chinese children: a retrospective study of age-specific prevalence. PLoS ONE 9, e99857 Google Scholar