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請用此 Handle URI 來引用此文件: http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/47928
完整後設資料紀錄
DC 欄位值語言
dc.contributor.advisor張麗冠(Li-Kwan Chang)
dc.contributor.authorChien-Sin Chenen
dc.contributor.author陳建炘zh_TW
dc.date.accessioned2021-06-15T06:43:05Z-
dc.date.available2016-07-25
dc.date.copyright2011-07-25
dc.date.issued2011
dc.date.submitted2011-07-06
dc.identifier.citation1. Epstein, M.A., B.G. Achong, and Y.M. Barr, Virus Particles in Cultured Lymphoblasts from Burkitt's Lymphoma. Lancet, 1964. 1(7335): 702-3.
2. Henle, G. and W. Henle, Immunofluorescence in cells derived from Burkitt's lymphoma. J Bacteriol, 1966. 91(3): 1248-56.
3. Young, L.S. and A.B. Rickinson, Epstein-Barr virus: 40 years on. Nat Rev Cancer, 2004. 4(10): 757-68.
4. Andersson-Anvret, M., et al., Relationship between the Epstein-Barr virus genome and nasopharyngeal carcinoma in Caucasian patients. Int J Cancer, 1979. 23(6): 762-7.
5. Weiss, L.M., et al., Detection of Epstein-Barr viral genomes in Reed-Sternberg cells of Hodgkin's disease. N Engl J Med, 1989. 320(8): 502-6.
6. Crawford, D.H., Biology and disease associations of Epstein-Barr virus. Philos Trans R Soc Lond B Biol Sci, 2001. 356(1408): 461-73.
7. Baer, R., et al., DNA sequence and expression of the B95-8 Epstein-Barr virus genome. Nature, 1984. 310(5974): 207-11.
8. de Jesus, O., et al., Updated Epstein-Barr virus (EBV) DNA sequence and analysis of a promoter for the BART (CST, BARF0) RNAs of EBV. J Gen Virol, 2003. 84(Pt 6): 1443-50.
9. Arrand, J.R., et al., Molecular cloning of the complete Epstein-Barr virus genome as a set of overlapping restriction endonuclease fragments. Nucleic Acids Res, 1981. 9(13): 2999-3014.
10. Dolyniuk, M., R. Pritchett, and E. Kieff, Proteins of Epstein-Barr virus. I. Analysis of the polypeptides of purified enveloped Epstein-Barr virus. J Virol, 1976. 17(3): 935-49.
11. Dolyniuk, M., E. Wolff, and E. Kieff, Proteins of Epstein-Barr Virus. II. Electrophoretic analysis of the polypeptides of the nucleocapsid and the glucosamine- and polysaccharide-containing components of enveloped virus. J Virol, 1976. 18(1): 289-97.
12. Sixbey, J.W., et al., Epstein-Barr virus replication in oropharyngeal epithelial cells. N Engl J Med, 1984. 310(19): 1225-30.
13. Nilsson, K., et al., The establishment of lymphoblastoid lines from adult and fetal human lymphoid tissue and its dependence on EBV. Int J Cancer, 1971. 8(3): 443-50.
14. Nonoyama, M., et al., DNA of Epstein-Barr virus detected in tissue of Burkitt's lymphoma and nasopharyngeal carcinoma. Proc Natl Acad Sci U S A, 1973. 70(11): 3265-8.
15. Nemerow, G.R., et al., Identification of gp350 as the viral glycoprotein mediating attachment of Epstein-Barr virus (EBV) to the EBV/C3d receptor of B cells: sequence homology of gp350 and C3 complement fragment C3d. J Virol, 1987. 61(5): 1416-20.
16. Molesworth, S.J., et al., Epstein-Barr virus gH is essential for penetration of B cells but also plays a role in attachment of virus to epithelial cells. J Virol, 2000. 74(14): 6324-32.
17. Borza, C.M. and L.M. Hutt-Fletcher, Alternate replication in B cells and epithelial cells switches tropism of Epstein-Barr virus. Nat Med, 2002. 8(6): 594-9.
18. Connolly, S.A., et al., Fusing structure and function: a structural view of the herpesvirus entry machinery. Nat Rev Microbiol, 2011. 9(5): 369-81.
19. Kanavaros, P., et al., Nasal T-cell lymphoma: a clinicopathologic entity associated with peculiar phenotype and with Epstein-Barr virus. Blood, 1993. 81(10): 2688-95.
20. Jones, J.F., et al., T-cell lymphomas containing Epstein-Barr viral DNA in patients with chronic Epstein-Barr virus infections. N Engl J Med, 1988. 318(12): 733-41.
21. Harabuchi, Y., et al., Epstein-Barr virus in nasal T-cell lymphomas in patients with lethal midline granuloma. Lancet, 1990. 335(8682): 128-30.
22. Bajaj, B.G., M. Murakami, and E.S. Robertson, Molecular biology of EBV in relationship to AIDS-associated oncogenesis. Cancer Treat Res, 2007. 133: 141-62.
23. Amon, W. and P.J. Farrell, Reactivation of Epstein-Barr virus from latency. Rev Med Virol, 2005. 15(3): 149-56.
24. Adams, A., Replication of latent Epstein-Barr virus genomes in Raji cells. J Virol, 1987. 61(5): 1743-6.
25. Yates, J.L. and N. Guan, Epstein-Barr virus-derived plasmids replicate only once per cell cycle and are not amplified after entry into cells. J Virol, 1991. 65(1): 483-8.
26. Kirchmaier, A.L. and B. Sugden, Plasmid maintenance of derivatives of oriP of Epstein-Barr virus. J Virol, 1995. 69(2): 1280-3.
27. Yates, J., et al., A cis-acting element from the Epstein-Barr viral genome that permits stable replication of recombinant plasmids in latently infected cells. Proc Natl Acad Sci U S A, 1984. 81(12): 3806-10.
28. Yates, J.L., N. Warren, and B. Sugden, Stable replication of plasmids derived from Epstein-Barr virus in various mammalian cells. Nature, 1985. 313(6005): 812-5.
29. Allday, M.J., D.H. Crawford, and B.E. Griffin, Epstein-Barr virus latent gene expression during the initiation of B cell immortalization. J Gen Virol, 1989. 70 ( Pt 7): 1755-64.
30. Cai, X., et al., Epstein-Barr virus microRNAs are evolutionarily conserved and differentially expressed. PLoS Pathog, 2006. 2(3): e23.
31. Pfeffer, S., et al., Identification of virus-encoded microRNAs. Science, 2004. 304(5671): 734-6.
32. Yenamandra, S.P., G. Klein, and E. Kashuba, Nuclear receptors and their role in Epstein -- Barr virus induced B cell transformation. Exp Oncol, 2009. 31(2): 67-73.
33. Young, L.S. and P.G. Murray, Epstein-Barr virus and oncogenesis: from latent genes to tumours. Oncogene, 2003. 22(33): 5108-21.
34. Pattle, S.B. and P.J. Farrell, The role of Epstein-Barr virus in cancer. Expert Opin Biol Ther, 2006. 6(11): 1193-205.
35. Maeda, E., et al., Spectrum of Epstein-Barr virus-related diseases: a pictorial review. Jpn J Radiol, 2009. 27(1): 4-19.
36. Henderson, E.E. and W.K. Long, Host cell reactivation of uv- and X-ray-damaged herpes simplex virus by Epstein-Barr virus (EBV)-transformed lymphoblastoid cell lines. Virology, 1981. 115(2): 237-48.
37. Nutter, L.M., et al., Induction of virus enzymes by phorbol esters and n-butyrate in Epstein-Barr virus genome-carrying Raji cells. Cancer Res, 1987. 47(16): 4407-12.
38. Luka, J., B. Kallin, and G. Klein, Induction of the Epstein-Barr virus (EBV) cycle in latently infected cells by n-butyrate. Virology, 1979. 94(1): 228-31.
39. Kallin, B., J. Luka, and G. Klein, Immunochemical characterization of Epstein-Barr virus-associated early and late antigens in n-butyrate-treated P3HR-1 cells. J Virol, 1979. 32(3): 710-6.
40. zur Hausen, H., et al., Persisting oncogenic herpesvirus induced by the tumour promotor TPA. Nature, 1978. 272(5651): 373-5.
41. Flemington, E. and S.H. Speck, Identification of phorbol ester response elements in the promoter of Epstein-Barr virus putative lytic switch gene BZLF1. J Virol, 1990. 64(3): 1217-26.
42. Chang, L.K. and S.T. Liu, Activation of the BRLF1 promoter and lytic cycle of Epstein-Barr virus by histone acetylation. Nucleic Acids Res, 2000. 28(20): 3918-25.
43. Jiang, J.H., et al., Hypoxia can contribute to the induction of the Epstein-Barr virus (EBV) lytic cycle. J Clin Virol, 2006. 37(2): 98-103.
44. Tovey, M.G., G. Lenoir, and J. Begon-Lours, Activation of latent Epstein-Barr virus by antibody to human IgM. Nature, 1978. 276(5685): 270-2.
45. Countryman, J., et al., Stimulus duration and response time independently influence the kinetics of lytic cycle reactivation of Epstein-Barr virus. J Virol, 2009. 83(20): 10694-709.
46. Schuster, C., S. Chasserot-Golaz, and G. Beck, Activation of Epstein-Barr virus promoters by a growth-factor and a glucocorticoid. FEBS Lett, 1991. 284(1): 82-6.
47. Countryman, J. and G. Miller, Activation of expression of latent Epstein-Barr herpesvirus after gene transfer with a small cloned subfragment of heterogeneous viral DNA. Proc Natl Acad Sci U S A, 1985. 82(12): 4085-9.
48. Flemington, E. and S.H. Speck, Autoregulation of Epstein-Barr virus putative lytic switch gene BZLF1. J Virol, 1990. 64(3): 1227-32.
49. Sinclair, A.J., et al., Pathways of activation of the Epstein-Barr virus productive cycle. J Virol, 1991. 65(5): 2237-44.
50. Ragoczy, T. and G. Miller, Autostimulation of the Epstein-Barr virus BRLF1 promoter is mediated through consensus Sp1 and Sp3 binding sites. J Virol, 2001. 75(11): 5240-51.
51. Chang, L.K., et al., Activation of Sp1-mediated transcription by Rta of Epstein-Barr virus via an interaction with MCAF1. Nucleic Acids Res, 2005. 33(20): 6528-39.
52. Ragoczy, T., L. Heston, and G. Miller, The Epstein-Barr virus Rta protein activates lytic cycle genes and can disrupt latency in B lymphocytes. J Virol, 1998. 72(10): 7978-84.
53. Zalani, S., E. Holley-Guthrie, and S. Kenney, Epstein-Barr viral latency is disrupted by the immediate-early BRLF1 protein through a cell-specific mechanism. Proc Natl Acad Sci U S A, 1996. 93(17): 9194-9.
54. Mannick, J.B., et al., Nitric oxide produced by human B lymphocytes inhibits apoptosis and Epstein-Barr virus reactivation. Cell, 1994. 79(7): 1137-46.
55. Chang, L.K., et al., Inhibition of Epstein-Barr virus lytic cycle by (-)-epigallocatechin gallate. Biochem Biophys Res Commun, 2003. 301(4): 1062-8.
56. Chang, F.R., et al., Inhibition of the Epstein-Barr virus lytic cycle by moronic acid. Antiviral Res, 2010. 85(3): 490-5.
57. Lin, T.P., et al., Inhibition of the epstein-barr virus lytic cycle by andrographolide. Biol Pharm Bull, 2008. 31(11): 2018-23.
58. Kawanishi, M., Nitric oxide inhibits Epstein-Barr virus DNA replication and activation of latent EBV. Intervirology, 1995. 38(3-4): 206-13.
59. Manet, E., et al., Epstein-Barr virus bicistronic mRNAs generated by facultative splicing code for two transcriptional trans-activators. EMBO J, 1989. 8(6): 1819-26.
60. Liu, P. and S.H. Speck, Synergistic autoactivation of the Epstein-Barr virus immediate-early BRLF1 promoter by Rta and Zta. Virology, 2003. 310(2): 199-206.
61. Chang, Y.N., et al., The Epstein-Barr virus Zta transactivator: a member of the bZIP family with unique DNA-binding specificity and a dimerization domain that lacks the characteristic heptad leucine zipper motif. J Virol, 1990. 64(7): 3358-69.
62. Farrell, P.J., et al., Epstein-Barr virus BZLF1 trans-activator specifically binds to a consensus AP-1 site and is related to c-fos. EMBO J, 1989. 8(1): 127-32.
63. Lieberman, P.M., J.M. Hardwick, and S.D. Hayward, Responsiveness of the Epstein-Barr virus NotI repeat promoter to the Z transactivator is mediated in a cell-type-specific manner by two independent signal regions. J Virol, 1989. 63(7): 3040-50.
64. Quinlivan, E.B., et al., Direct BRLF1 binding is required for cooperative BZLF1/BRLF1 activation of the Epstein-Barr virus early promoter, BMRF1. Nucleic Acids Res, 1993. 21(14): 1999-2007.
65. Lee, Y.H., et al., Activation of the ERK signal transduction pathway by Epstein-Barr virus immediate-early protein Rta. J Gen Virol, 2008. 89(Pt 10): 2437-46.
66. Chen, C., D. Li, and N. Guo, Regulation of cellular and viral protein expression by the Epstein-Barr virus transcriptional regulator Zta: implications for therapy of EBV associated tumors. Cancer Biol Ther, 2009. 8(11): 987-95.
67. Decaussin, G., V. Leclerc, and T. Ooka, The lytic cycle of Epstein-Barr virus in the nonproducer Raji line can be rescued by the expression of a 135-kilodalton protein encoded by the BALF2 open reading frame. J Virol, 1995. 69(11): 7309-14.
68. Tsurumi, T., et al., Epstein-Barr virus single-stranded DNA-binding protein: purification, characterization, and action on DNA synthesis by the viral DNA polymerase. Virology, 1996. 222(2): 352-64.
69. Nakayama, S., et al., Epstein-Barr virus polymerase processivity factor enhances BALF2 promoter transcription as a coactivator for the BZLF1 immediate-early protein. J Biol Chem, 2009. 284(32): 21557-68.
70. Liu, C., N.D. Sista, and J.S. Pagano, Activation of the Epstein-Barr virus DNA polymerase promoter by the BRLF1 immediate-early protein is mediated through USF and E2F. J Virol, 1996. 70(4): 2545-55.
71. Tsurumi, T., T. Daikoku, and Y. Nishiyama, Further characterization of the interaction between the Epstein-Barr virus DNA polymerase catalytic subunit and its accessory subunit with regard to the 3'-to-5' exonucleolytic activity and stability of initiation complex at primer terminus. J Virol, 1994. 68(5): 3354-63.
72. Daibata, M. and T. Sairenji, Epstein-Barr virus (EBV) replication and expressions of EA-D (BMRF1 gene product), virus-specific deoxyribonuclease, and DNA polymerase in EBV-activated Akata cells. Virology, 1993. 196(2): 900-4.
73. Kiehl, A. and D.I. Dorsky, Cooperation of EBV DNA polymerase and EA-D(BMRF1) in vitro and colocalization in nuclei of infected cells. Virology, 1991. 184(1): 330-40.
74. Neuhierl, B. and H.J. Delecluse, The Epstein-Barr virus BMRF1 gene is essential for lytic virus replication. J Virol, 2006. 80(10): 5078-81.
75. Zhang, Q., et al., Functional and physical interactions between the Epstein-Barr virus (EBV) proteins BZLF1 and BMRF1: Effects on EBV transcription and lytic replication. J Virol, 1996. 70(8): 5131-42.
76. Fixman, E.D., G.S. Hayward, and S.D. Hayward, trans-acting requirements for replication of Epstein-Barr virus ori-Lyt. J Virol, 1992. 66(8): 5030-9.
77. Yokoyama, N., et al., Assembly of the epstein-barr virus BBLF4, BSLF1 and BBLF2/3 proteins and their interactive properties. J Gen Virol, 1999. 80 ( Pt 11): 2879-87.
78. Fujii, K., et al., The Epstein-Barr virus pol catalytic subunit physically interacts with the BBLF4-BSLF1-BBLF2/3 complex. J Virol, 2000. 74(6): 2550-7.
79. Chen, L.W., et al., Marked variation in response of consensus binding elements for the Rta protein of Epstein-Barr virus. J Virol, 2005. 79(15): 9635-50.
80. Edson, C.M. and D.A. Thorley-Lawson, Epstein-Barr virus membrane antigens: characterization, distribution, and strain differences. J Virol, 1981. 39(1): 172-84.
81. Kurilla, M.G., et al., A novel Epstein-Barr virus glycoprotein gp150 expressed from the BDLF3 open reading frame. Virology, 1995. 209(1): 108-21.
82. Nolan, L.A. and A.J. Morgan, The Epstein-Barr virus open reading frame BDLF3 codes for a 100-150 kDa glycoprotein. J Gen Virol, 1995. 76 ( Pt 6): 1381-92.
83. Henson, B.W., et al., Self-assembly of Epstein-Barr virus capsids. J Virol, 2009. 83(8): 3877-90.
84. Wang, W.H., L.K. Chang, and S.T. Liu, Molecular interactions of Epstein-Barr virus capsid proteins. J Virol, 2011. 85(4): 1615-24.
85. Biggin, M., et al., Epstein-Barr virus gene expression in P3HR1-superinfected Raji cells. J Virol, 1987. 61(10): 3120-32.
86. Flemington, E.K., A.E. Goldfeld, and S.H. Speck, Efficient transcription of the Epstein-Barr virus immediate-early BZLF1 and BRLF1 genes requires protein synthesis. J Virol, 1991. 65(12): 7073-7.
87. Holley-Guthrie, E.A., et al., The Epstein-Barr virus (EBV) BMRF1 promoter for early antigen (EA-D) is regulated by the EBV transactivators, BRLF1 and BZLF1, in a cell-specific manner. J Virol, 1990. 64(8): 3753-9.
88. Chevallier-Greco, A., et al., The Epstein-Barr virus (EBV) DR enhancer contains two functionally different domains: domain A is constitutive and cell specific, domain B is transactivated by the EBV early protein R. J Virol, 1989. 63(2): 615-23.
89. Cox, M.A., J. Leahy, and J.M. Hardwick, An enhancer within the divergent promoter of Epstein-Barr virus responds synergistically to the R and Z transactivators. J Virol, 1990. 64(1): 313-21.
90. Chang, L.K., et al., MCAF1 and synergistic activation of the transcription of Epstein-Barr virus lytic genes by Rta and Zta. Nucleic Acids Res, 2010. 38(14): 4687-700.
91. Feederle, R., et al., The Epstein-Barr virus lytic program is controlled by the co-operative functions of two transactivators. EMBO J, 2000. 19(12): 3080-9.
92. Chiu, Y.F., et al., A comprehensive library of mutations of Epstein Barr virus. J Gen Virol, 2007. 88(Pt 9): 2463-72.
93. Kerppola, T.K. and T. Curran, Selective DNA bending by a variety of bZIP proteins. Mol Cell Biol, 1993. 13(9): 5479-89.
94. Leonard, D.A., N. Rajaram, and T.K. Kerppola, Structural basis of DNA bending and oriented heterodimer binding by the basic leucine zipper domains of Fos and Jun. Proc Natl Acad Sci U S A, 1997. 94(10): 4913-8.
95. Lieberman, P.M., et al., The zta transactivator involved in induction of lytic cycle gene expression in Epstein-Barr virus-infected lymphocytes binds to both AP-1 and ZRE sites in target promoter and enhancer regions. J Virol, 1990. 64(3): 1143-55.
96. Cayrol, C. and E.K. Flemington, Identification of cellular target genes of the Epstein-Barr virus transactivator Zta: activation of transforming growth factor beta igh3 (TGF-beta igh3) and TGF-beta 1. J Virol, 1995. 69(7): 4206-12.
97. Sato, H., et al., Concatameric replication of Epstein-Barr virus: structure of the termini in virus-producer and newly transformed cell lines. J Virol, 1990. 64(11): 5295-300.
98. Kolman, J.L., et al., Comparing transcriptional activation and autostimulation by ZEBRA and ZEBRA/c-Fos chimeras. J Virol, 1996. 70(3): 1493-504.
99. Le Roux, F., A. Sergeant, and L. Corbo, Epstein-Barr virus (EBV) EB1/Zta protein provided in trans and competent for the activation of productive cycle genes does not activate the BZLF1 gene in the EBV genome. J Gen Virol, 1996. 77 ( Pt 3): 501-9.
100. Lieberman, P.M. and A.J. Berk, The Zta trans-activator protein stabilizes TFIID association with promoter DNA by direct protein-protein interaction. Genes Dev, 1991. 5(12B): 2441-54.
101. Lieberman, P., Identification of functional targets of the Zta transcriptional activator by formation of stable preinitiation complex intermediates. Mol Cell Biol, 1994. 14(12): 8365-75.
102. Michaud, F., et al., Epstein-Barr virus interferes with the amplification of IFNalpha secretion by activating suppressor of cytokine signaling 3 in primary human monocytes. PLoS One, 2010. 5(7): e11908.
103. Morrison, T.E., et al., Inhibition of IFN-gamma signaling by an Epstein-Barr virus immediate-early protein. Immunity, 2001. 15(5): 787-99.
104. Cayrol, C. and E.K. Flemington, The Epstein-Barr virus bZIP transcription factor Zta causes G0/G1 cell cycle arrest through induction of cyclin-dependent kinase inhibitors. EMBO J, 1996. 15(11): 2748-59.
105. Dreyfus, D.H., et al., Stable expression of Epstein-Barr virus BZLF-1-encoded ZEBRA protein activates p53-dependent transcription in human Jurkat T-lymphoblastoid cells. Blood, 2000. 96(2): 625-34.
106. Rodriguez, A., et al., Genetic dissection of cell growth arrest functions mediated by the Epstein-Barr virus lytic gene product, Zta. J Virol, 1999. 73(11): 9029-38.
107. Wu, F.Y., et al., CCAAT/enhancer binding protein alpha interacts with ZTA and mediates ZTA-induced p21(CIP-1) accumulation and G(1) cell cycle arrest during the Epstein-Barr virus lytic cycle. J Virol, 2003. 77(2): 1481-500.
108. Sato, Y., et al., Degradation of phosphorylated p53 by viral protein-ECS E3 ligase complex. PLoS Pathog, 2009. 5(7): e1000530.
109. Guo, Q., et al., Transactivators Zta and Rta of Epstein-Barr virus promote G0/G1 to S transition in Raji cells: a novel relationship between lytic virus and cell cycle. Mol Immunol, 2010. 47(9): 1783-92.
110. Adamson, A.L. and S. Kenney, Epstein-barr virus immediate-early protein BZLF1 is SUMO-1 modified and disrupts promyelocytic leukemia bodies. J Virol, 2001. 75(5): 2388-99.
111. Adamson, A.L., Effects of SUMO-1 upon Epstein-Barr virus BZLF1 function and BMRF1 expression. Biochem Biophys Res Commun, 2005. 336(1): 22-8.
112. Gruffat, H., E. Manet, and A. Sergeant, MEF2-mediated recruitment of class II HDAC at the EBV immediate early gene BZLF1 links latency and chromatin remodeling. EMBO Rep, 2002. 3(2): 141-6.
113. Kudoh, A., et al., Epstein-Barr virus lytic replication elicits ATM checkpoint signal transduction while providing an S-phase-like cellular environment. J Biol Chem, 2005. 280(9): 8156-63.
114. Chen, C.C., et al., Enhancement of Zta-activated lytic transcription of Epstein-Barr virus by Ku80. J Gen Virol, 2011. 92(Pt 3): 661-8.
115. Bailey, S.G., et al., Functional interaction between Epstein-Barr virus replication protein Zta and host DNA damage response protein 53BP1. J Virol, 2009. 83(21): 11116-22.
116. Chang, Y., et al., Induction of the early growth response 1 gene by Epstein-Barr virus lytic transactivator Zta. J Virol, 2006. 80(15): 7748-55.
117. Heather, J., et al., 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(Pt 6): 1450-4.
118. Bhende, P.M., et al., The EBV lytic switch protein, Z, preferentially binds to and activates the methylated viral genome. Nat Genet, 2004. 36(10): 1099-104.
119. Bhende, P.M., et al., BZLF1 activation of the methylated form of the BRLF1 immediate-early promoter is regulated by BZLF1 residue 186. J Virol, 2005. 79(12): 7338-48.
120. Karlsson, Q.H., et al., Methylated DNA recognition during the reversal of epigenetic silencing is regulated by cysteine and serine residues in the Epstein-Barr virus lytic switch protein. PLoS Pathog, 2008. 4(3): e1000005.
121. Karlsson, Q.H., et al., The reversal of epigenetic silencing of the EBV genome is regulated by viral bZIP protein. Biochem Soc Trans, 2008. 36(Pt 4): 637-9.
122. Dickerson, S.J., et al., Methylation-dependent binding of the epstein-barr virus BZLF1 protein to viral promoters. PLoS Pathog, 2009. 5(3): e1000356.
123. Kalla, M., et al., 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 U S A, 2010. 107(2): 850-5.
124. Bergbauer, M., et al., CpG-methylation regulates a class of Epstein-Barr virus promoters. PLoS Pathog, 2010. 6(9).
125. Manet, E., et al., Domains of the Epstein-Barr virus (EBV) transcription factor R required for dimerization, DNA binding and activation. Nucleic Acids Res, 1991. 19(10): 2661-7.
126. Chen, L.W., et al., Two phenylalanines in the C-terminus of Epstein-Barr virus Rta protein reciprocally modulate its DNA binding and transactivation function. Virology, 2009. 386(2): 448-61.
127. Hardwick, J.M., P.M. Lieberman, and S.D. Hayward, A new Epstein-Barr virus transactivator, R, induces expression of a cytoplasmic early antigen. J Virol, 1988. 62(7): 2274-84.
128. Gruffat, H., et al., Characterization of an R-binding site mediating the R-induced activation of the Epstein-Barr virus BMLF1 promoter. J Virol, 1992. 66(1): 46-52.
129. Gruffat, H., et al., The enhancer factor R of Epstein-Barr virus (EBV) is a sequence-specific DNA binding protein. Nucleic Acids Res, 1990. 18(23): 6835-43.
130. Hung, C.H. and S.T. Liu, Characterization of the Epstein-Barr virus BALF2 promoter. J Gen Virol, 1999. 80 ( Pt 10): 2747-50.
131. Kenney, S., et al., The Epstein-Barr virus BMLF1 promoter contains an enhancer element that is responsive to the BZLF1 and BRLF1 transactivators. J Virol, 1989. 63(9): 3878-83.
132. Lukac, D.M., et al., Reactivation of Kaposi's sarcoma-associated herpesvirus infection from latency by expression of the ORF 50 transactivator, a homolog of the EBV R protein. Virology, 1998. 252(2): 304-12.
133. Zhu, F.X., T. Cusano, and Y. Yuan, Identification of the immediate-early transcripts of Kaposi's sarcoma-associated herpesvirus. J Virol, 1999. 73(7): 5556-67.
134. Chen, Y.J., et al., Epstein-Barr Virus (EBV) Rta-Mediated EBV and Kaposi's Sarcoma-Associated Herpesvirus Lytic Reactivations in 293 Cells. PLoS One, 2011. 6(3): e17809.
135. Ho, C.H., et al., Epstein-Barr virus transcription activator Rta upregulates decoy receptor 3 expression by binding to its promoter. J Virol, 2007. 81(9): 4837-47.
136. Gutsch, D.E., K.B. Marcu, and S.C. Kenney, The Epstein-Barr virus BRLF1 gene product transactivates the murine and human c-myc promoters. Cell Mol Biol (Noisy-le-grand), 1994. 40(6): 747-60.
137. Li, Y., et al., The C-mer gene is induced by Epstein-Barr virus immediate-early protein BRLF1. J Virol, 2004. 78(21): 11778-85.
138. Li, Y., et al., Fatty acid synthase expression is induced by the Epstein-Barr virus immediate-early protein BRLF1 and is required for lytic viral gene expression. J Virol, 2004. 78(8): 4197-206.
139. Darr, C.D., A. Mauser, and S. Kenney, 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(13): 6135-42.
140. Zacny, V.L., J. Wilson, and J.S. Pagano, The Epstein-Barr virus immediate-early gene product, BRLF1, interacts with the retinoblastoma protein during the viral lytic cycle. J Virol, 1998. 72(10): 8043-51.
141. Swenson, J.J., et al., The Epstein-Barr virus protein BRLF1 activates S phase entry through E2F1 induction. J Virol, 1999. 73(8): 6540-50.
142. Swenson, J.J., E. Holley-Guthrie, and S.C. Kenney, Epstein-Barr virus immediate-early protein BRLF1 interacts with CBP, promoting enhanced BRLF1 transactivation. J Virol, 2001. 75(13): 6228-34.
143. Chang, L.K., et al., Post-translational modification of Rta of Epstein-Barr virus by SUMO-1. J Biol Chem, 2004. 279(37): 38803-12.
144. Liu, S.T., et al., Sumoylation of Rta of Epstein-Barr virus is preferentially enhanced by PIASxbeta. Virus Res, 2006. 119(2): 163-70.
145. Chang, L.K., et al., Enhancement of transactivation activity of Rta of Epstein-Barr virus by RanBPM. J Mol Biol, 2008. 379(2): 231-42.
146. Calderwood, M.A., et al., Epstein-Barr virus and virus human protein interaction maps. Proc Natl Acad Sci U S A, 2007. 104(18): 7606-11.
147. Calderwood, M.A., A.M. Holthaus, and E. Johannsen, The Epstein-Barr virus LF2 protein inhibits viral replication. J Virol, 2008. 82(17): 8509-19.
148. Heilmann, A.M., M.A. Calderwood, and E. Johannsen, Epstein-Barr virus LF2 protein regulates viral replication by altering Rta subcellular localization. J Virol, 2010. 84(19): 9920-31.
149. Hsu, T.Y., et al., Reactivation of Epstein-Barr virus can be triggered by an Rta protein mutated at the nuclear localization signal. J Gen Virol, 2005. 86(Pt 2): 317-22.
150. Chang, Y., et al., Induction of Epstein-Barr virus latent membrane protein 1 by a lytic transactivator Rta. J Virol, 2004. 78(23): 13028-36.
151. Zhang, J., et al., The latent membrane protein 1 of Epstein-Barr virus establishes an antiviral state via induction of interferon-stimulated genes. J Biol Chem, 2004. 279(44): 46335-42.
152. Xu, D., K. Brumm, and L. Zhang, The latent membrane protein 1 of Epstein-Barr virus (EBV) primes EBV latency cells for type I interferon production. J Biol Chem, 2006. 281(14): 9163-9.
153. Ho, C.H., et al., Decoy receptor 3, upregulated by Epstein-Barr virus latent membrane protein 1, enhances nasopharyngeal carcinoma cell migration and invasion. Carcinogenesis, 2009. 30(8): 1443-51.
154. Hammerschmidt, W. and B. Sugden, Identification and characterization of oriLyt, a lytic origin of DNA replication of Epstein-Barr virus. Cell, 1988. 55(3): 427-33.
155. Schepers, A., D. Pich, and W. Hammerschmidt, A transcription factor with homology to the AP-1 family links RNA transcription and DNA replication in the lytic cycle of Epstein-Barr virus. EMBO J, 1993. 12(10): 3921-9.
156. Schepers, A., D. Pich, and W. Hammerschmidt, Activation of oriLyt, the lytic origin of DNA replication of Epstein-Barr virus, by BZLF1. Virology, 1996. 220(2): 367-76.
157. Tsurumi, T., Purification and characterization of the DNA-binding activity of the Epstein-Barr virus DNA polymerase accessory protein BMRF1 gene products, as expressed in insect cells by using the baculovirus system. J Virol, 1993. 67(3): 1681-7.
158. Tsurumi, T., et al., Functional expression and characterization of the Epstein-Barr virus DNA polymerase catalytic subunit. J Virol, 1993. 67(8): 4651-8.
159. Tsurumi, T., et al., Functional interaction between Epstein-Barr virus DNA polymerase catalytic subunit and its accessory subunit in vitro. J Virol, 1993. 67(12): 7648-53.
160. Tsurumi, T., et al., Overexpression, purification and helix-destabilizing properties of Epstein-Barr virus ssDNA-binding protein. J Gen Virol, 1998. 79 ( Pt 5): 1257-64.
161. Kudoh, A., et al., Homologous recombinational repair factors are recruited and loaded onto the viral DNA genome in Epstein-Barr virus replication compartments. J Virol, 2009. 83(13): 6641-51.
162. Datta, A.K., et al., Acyclovir inhibition of Epstein-Barr virus replication. Proc Natl Acad Sci U S A, 1980. 77(9): 5163-6.
163. Goldstein, G., et al., Isolation of a polypeptide that has lymphocyte-differentiating properties and is probably represented universally in living cells. Proc Natl Acad Sci U S A, 1975. 72(1): 11-5.
164. Schlesinger, D.H., G. Goldstein, and H.D. Niall, The complete amino acid sequence of ubiquitin, an adenylate cyclase stimulating polypeptide probably universal in living cells. Biochemistry, 1975. 14(10): 2214-8.
165. Goldknopf, I.L., et al., Presence of protein A24 in rat liver nucleosomes. Proc Natl Acad Sci U S A, 1977. 74(12): 5492-5.
166. Hunt, L.T. and M.O. Dayhoff, Amino-terminal sequence identity of ubiquitin and the nonhistone component of nuclear protein A24. Biochem Biophys Res Commun, 1977. 74(2): 650-5.
167. Fang, S. and A.M. Weissman, A field guide to ubiquitylation. Cell Mol Life Sci, 2004. 61(13): 1546-61.
168. Clague, M.J. and S. Urbe, Ubiquitin: same molecule, different degradation pathways. Cell, 2010. 143(5): 682-5.
169. Ulrich, H.D. and H. Walden, Ubiquitin signalling in DNA replication and repair. Nat Rev Mol Cell Biol, 2010. 11(7): 479-89.
170. Grabbe, C., K. Husnjak, and I. Dikic, The spatial and temporal organization of ubiquitin networks. Nat Rev Mol Cell Biol, 2011.
171. Schoenheimer, R. and H.T. Clarke, The dynamic state of body constituents. Harvard University monographs in medicine and public health [No. 3]. 1942, Cambridge, Mass.,: Harvard university press. 3 p., 3 l., 3 -78 p., 2 l.
172. Simpson, M.V., The release of labeled amino acids from the proteins of rat liver slices. J Biol Chem, 1953. 201(1): 143-54.
173. Hershko, A. and G.M. Tomkins, Studies on the degradation of tyrosine aminotransferase in hepatoma cells in culture. Influence of the composition of the medium and adenosine triphosphate dependence. J Biol Chem, 1971. 246(3): 710-4.
174. Etlinger, J.D. and A.L. Goldberg, A soluble ATP-dependent proteolytic system responsible for the degradation of abnormal proteins in reticulocytes. Proc Natl Acad Sci U S A, 1977. 74(1): 54-8.
175. Ciehanover, A., Y. Hod, and A. Hershko, A heat-stable polypeptide component of an ATP-dependent proteolytic system from reticulocytes. Biochem Biophys Res Commun, 1978. 81(4): 1100-5.
176. Hershko, A., A. Ciechanover, and I.A. Rose, Resolution of the ATP-dependent proteolytic system from reticulocytes: a component that interacts with ATP. Proc Natl Acad Sci U S A, 1979. 76(7): 3107-10.
177. Ciechanover, A., et al., ATP-dependent conjugation of reticulocyte proteins with the polypeptide required for protein degradation. Proc Natl Acad Sci U S A, 1980. 77(3): 1365-8.
178. Hershko, A., et al., Proposed role of ATP in protein breakdown: conjugation of protein with multiple chains of the polypeptide of ATP-dependent proteolysis. Proc Natl Acad Sci U S A, 1980. 77(4): 1783-6.
179. Wilkinson, K.D., M.K. Urban, and A.L. Haas, Ubiquitin is the ATP-dependent proteolysis factor I of rabbit reticulocytes. J Biol Chem, 1980. 255(16): 7529-32.
180. Breitschopf, K., et al., A novel site for ubiquitination: the N-terminal residue, and not internal lysines of MyoD, is essential for conjugation and degradation of the protein. EMBO J, 1998. 17(20): 5964-73.
181. Hershko, A. and A. Ciechanover, The ubiquitin system. Annu Rev Biochem, 1998. 67: 425-79.
182. Aviel, S., et al., Degradation of the epstein-barr virus latent membrane protein
dc.identifier.urihttp://tdr.lib.ntu.edu.tw/jspui/handle/123456789/47928-
dc.description.abstract極早期蛋白質Rta是促進Epstein-Barr virus (EBV) 進入溶裂循環時很重要的轉錄因子。Tripartite-motif 5 alpha (TRIM5alpha) 是反轉錄病毒限制因子 (restriction factor),具有泛素E3連接酶 (ubiquitin E3 ligase) 的活性,在特定靈長類中能保護宿主免於反轉錄病毒 (retrovirus) 的侵害。然而,目前報導中,TRIM5alpha的限制目標大都限於反轉錄病毒,而鮮少有DNA病毒。本研究發現人類的TRIM5alpha能與Rta在細胞質直接結合。兩者的交互作用透過Rta的N端序列與TRIM5alpha C端的B30.2功能區而發生。另外,TRIM5alpha會促進Rta的泛素化,若過量表現TRIM5alpha也會導致Rta的濃度降低及下游的轉錄活化遭到抑制,進而緩解EBV的溶裂循環。綜合以上,本研究第一個發現人類TRIM5alpha作用於DNA病毒的蛋白質上,透過與Rta的結合並促進其泛素化,使EBV的溶裂循環受到抑制。zh_TW
dc.description.abstractAn immediate-early protein, Rta, is an important transcription factor required for initiating the lytic cycle of Epstein-Barr virus (EBV). Tripartite-motif 5 alpha (TRIM5alpha) is a restriction factor of retroviruses with the ubiquitin E3 ligase activity, which protects primates form retrovirus infection in a species-specific manner. However, the documented target spectrum of TRIM5alpha was limited to RNA viruses. This study finds that TRIM5alpha is a binding partner of Rta and colocalizes with Rta in the cytoplasm. The interaction involves the N-terminal region in Rta and the C-terminal B30.2 domain in TRIM5alpha. Moreover, overexpression of TRIM5alpha facilitates the ubiquitination of Rta and reduces the level of Rta, thereby inhibiting the transactivation activity of Rta. Collectively, this study identifies Rta to be the first DNA viral target of human TRIM5alpha, and the interaction prevents EBV lytic progression by promoting Rta's ubiquitination.en
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dc.description.tableofcontents口試委員審定書.............................................................................................................I
誌謝...............................................................................................................................II
中文摘要……………………………………………………………………………..III
英文摘要……………………………………………………………………………..IV
常用縮寫表…………………………………………………………………………...V
前言……………………………………………………………………………………1
一、 Epstein-Barr virus (EBV)…………………………………………………...1
二、 EBV的生活史……………………………………………………………...2
EBV的潛伏期…………………………………………………………………...2
EBV的溶裂循環………………………………………………………………...2
三、 EBV的極早期基因………………………………………………………...3
轉錄因子Zta……………………………………………………………………..3
Zta與宿主蛋白質的互動………………………………………………………..4
Zta的特殊上位基因 (epigenetic) 調控…………………………………...……5
轉錄因子Rta……………………………………………………………………..5
Rta與宿主蛋白質的互動………………………………………………………..6
Rta轉錄活性的調控……………………………………………………………..6
Rta與免疫系統的關聯…………………………………………………………..7
四、 EBV的溶裂複製…………………………………………………………...8
五、 泛素與泛素化 (ubiquitin and ubiquitination)……………………………...8
泛素與泛素化機制的發現………………………………………………………9
泛素鏈結系統 (ubiquitin-conjugating system) 的作用機制…………………..9
泛素化的連結方式……………………………………………………………..10
泛素化調控的生理反應………………………………………………………..11
病毒與宿主泛素系統的對抗…………………………………………………..12
六、 限制因子 (restriction factors) tripartite motif 5 alpha (TRIM5alpha)………..12
人類免疫缺乏病毒1型 (human immunodeficiency virus 1, HIV-1)…………13
TRIM5alpha對HIV-1的限制作用…………………………………………………14
TRIM5alpha蛋白質的功能區……………………………………………………...14
TRIM5alpha限制能力的物種特異性……………………………………………...15
TRIMCyp……………………………………………………………………….16
TRIM5alpha的表現與分佈………………………………………………………...17
細胞膜狀系統及藥物處理對TRIM5alpha限制HIV-1的影響…………………..17
TRIM5alpha與IFN及NF-kappaB的免疫反應路徑…………………………………..18
EBV對IFN及NF-kappaB免疫反應路徑的調控…………………………………18
研究目的……………………………………………………………………………..19
材料與方法…………………………………………………………………………..20
一、 菌種與細胞株……………………………………………………………..20
二、 質體與抗體………………………………………………………………..20
三、 大腸桿菌轉型作用 (transformation)……………………………………..21
四、 質體DNA的萃取…………………………………………………………21
五、 細胞轉染 (transfection)…………………………………………………..21
六、 蛋白質誘導表現…………………………………………………………..21
七、 Glutathione S-transferase (GST) pull down assay………………………...22
八、 免疫沉澱法 (immunoprecipitation, IP)…………………………………..22
九、 免疫螢光染色 (immunefluorescence staining, IF staining)……………...22
十、 變性免疫沉澱法 (denature immunoprecipitation, denature IP)………….23
十一、 冷光報導基因分析 (luciferase reporter assay)………………………......24
十二、 西方點墨分析 (western blot analysis)……………………………………24

結果…………………………………………………………………………………..26
一、 篩選細胞內與Rta可能結合的宿主蛋白質……………………………...26
二、 TRIM5alpha與Rta在細胞體內結合………………………………………….26
三、 TRIM5alpha與Rta結合位於細胞質………………………………………….27
四、 TRIM5alpha與Rta在細胞體外直接結合…………………………………….28
五、 TRIM5alpha以C端與Rta的N端結合……………………………………….28
六、 TRIM5alpha促進Rta的泛素化……………………………………………….29
七、 抑制TRIM5alpha的表現同時會降低Rta的泛素化…………………………30
八、 TRIM5alpha抑制Rta對EBV早期基因BMLF1及BMRF1啟動子上RRE的轉錄活化………………………………………………………………………30
九、 EBV進入溶裂循環時,TRIM5alpha能使Rta總量降低,進而降低下游基因的表現…………………………………………………………………………31
十、 TRIM5alpha所促進Rta的泛素化不會導致Rta進入lysosomal/autophagosomal degradation pathway……………………………..32
十一、 過量表現TRIM5alpha會突破MG132對Rta的穩定作用…………………...33
討論…………………………………………………………………………………..34
圖表…………………………………………………………………………………..41
表1、本研究使用之質體………………………………………………………….41
表2、本研究使用之抗體………………………………………………………….46
圖1、EBV的生活史................................................................................................47
圖2、細胞內與Rta結合的蛋白質……………………………………………….49
圖3、TRIM5alpha與Rta在細胞內的結合…………………………………………...50
圖4、TRIM5alpha與Rta的免疫螢光分析…………………………………………...51
圖5、TRIM5alpha與Rta的免疫螢光分析…………………………………………...52
圖6、TRIM5alpha與Rta的體外結合………………………………………………...53
圖7、TRIM5alpha以蛋白質C端與Rta的N端結合……………………………….54
圖8、TRIM5alpha促進Rta的泛素化………………………………………………...56
圖9、抑制TRIM5alpha時會減低Rta的泛素化…………………………...………...57
圖10、TRIM5alpha會降低Rta對BMLF1及BMRF1啟動子的轉錄活化………...59
圖11、TRIM5alpha會使Rta的濃度降低,進而使EA-D表現量下降…………….60
圖12、TRIM5alpha濃度過高時,會使泛素化Rta的濃度降低…………………….61
圖13、proteasome抑制劑MG132無法復原高濃度TRIM5alpha所造成的Rta濃度
下降…………………………………………………………………...………….62
圖14、TRIM5alpha與Rta結合後可能的模型及在EBV生活史轉換上的意義…...63
參考文獻......................................................................................................................64
附錄…………………………………………………………………………………..90
附錄1、泛素鏈結系統 (ubiquitin-conjugating system)………………………….90
附錄2、TRIM家族蛋白質的結構特徵..................................................................92
附錄3、TRIM5alpha限制HIV-1同時活化NF-kappaB免疫反應路徑.............................93
附錄4、TRIM家族蛋白質調節免疫系統..............................................................94
附錄5、質譜儀鑑定Rta在細胞內可能結合的蛋白質.........................................95
dc.language.isozh-TW
dc.titleTRIM5alpha藉由促進Rta的泛素化緩解Epstein-Barr virus的溶裂循環zh_TW
dc.titleTRIM5alpha restrains Epstein-Barr virus lytic cycle by mediating ubiquitination of Rtaen
dc.typeThesis
dc.date.schoolyear99-2
dc.description.degree碩士
dc.contributor.oralexamcommittee劉世東,張沛鈞,張世宗
dc.subject.keywordEpstein-Barr virus (EBV),Rta,TRIM5alpha,泛素,泛素化,溶裂循環,zh_TW
dc.subject.keywordEpstein-Barr virus (EBV),Rta,TRIM5alpha,ubiquitin,ubiquitination,lytic cycle,en
dc.relation.page96
dc.rights.note有償授權
dc.date.accepted2011-07-06
dc.contributor.author-college生命科學院zh_TW
dc.contributor.author-dept生化科技學系zh_TW
顯示於系所單位:生化科技學系

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