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Chapter 15 : Viral Plasmids in Mammalian Cells

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Viral Plasmids in Mammalian Cells, Page 1 of 2

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Abstract:

Like bacteria and yeast, mammalian cells can harbor plasmids. These double-stranded circular DNA plasmids or episomes are the genomes of DNA viruses. The genomes of Epstein-Barr virus, the related Kaposi's sarcoma-associated (virus human herpesvirus 8), and papillomavirus can persist indefinitely in latently infected cells due to their ability to replicate and stably segregate during cell division, and this chapter focuses on these viruses. Efficient replication from the dyad symmetry (DS) element requires all four Epstein-Barr nuclear antigen (EBNA)1-binding sites as well as the nonamer repeats that flank the EBNA1 sites. EBNA1 is the only viral protein required to replicate and maintain plasmids and EBV episomes and does so through interactions with the 18-bp palindromic sequences present in the family of repeats (FR) and DS elements of . Replication from requires EBNA1 binding to the DS element, but this interaction alone does not activate the origin, as EBNA1 is bound to the DS throughout most of the cell cycle. The transient replication of bovine papillomavirus (BPV) genomes is dependent on the viral E1 and E2 proteins, and no other viral proteins are required. On the basis of this finding, a mouse cell line was developed that stably expressed E1 and E2 and was used to map the -acting requirements for BPV plasmid replication. The latent genomes of several different DNA viruses are stably maintained in mammalian cells as low-copy-number plasmids.

Citation: Frappier L. 2004. Viral Plasmids in Mammalian Cells, p 325-340. In Funnell B, Phillips G (ed), Plasmid Biology. ASM Press, Washington, DC. doi: 10.1128/9781555817732.ch15

Key Concept Ranking

DNA Synthesis
0.69607574
Human herpesvirus 8
0.4872788
DNA Replication
0.48436514
Memory B Cell
0.48188668
Human herpesvirus 1
0.45551676
0.69607574
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Figures

Image of Figure 1
Figure 1

Organization of EBV The positioning of the FR and DS elements in the EBV nucleotide sequence is shown at the top. Below is the nucleotide sequence of the DS clement showing the EBNA1-binding sites 1 to 4 (rectangles), the nonamer repeats (solid arrows), and the 65-bp dyad symmetry sequence (dashed arrows).

Citation: Frappier L. 2004. Viral Plasmids in Mammalian Cells, p 325-340. In Funnell B, Phillips G (ed), Plasmid Biology. ASM Press, Washington, DC. doi: 10.1128/9781555817732.ch15
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Image of Figure 2
Figure 2

Functional regions of the EBV KBNA1 protein. The regions of EBNA1 that are important for the DNA replication, segregation, and transcriptional activation functions are indicated by the shaded boxes; black shaded regions are essential, and lightly shaded regions contribute to but arc not required for the indicated function. DNA linking refers to the ability of EBNA1 dimers bound to the FR and DS elements to interact with each other, thereby linking the elements together. For DNA linking, the region responsible for the most stable KBNAI-FBNA1 interactions is marked by the black shading and the region that mediates less stable interactions is indicated by the light shading.

Citation: Frappier L. 2004. Viral Plasmids in Mammalian Cells, p 325-340. In Funnell B, Phillips G (ed), Plasmid Biology. ASM Press, Washington, DC. doi: 10.1128/9781555817732.ch15
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Image of Figure 3
Figure 3

Model of the segregation of viral episomes by chromosome attachment. EBNA1, LANA, and E2 bind the EBV, KSHV, and BPV viral episomes, respectively, and tether them to the cellular mitotic chromosomes by binding to a cellular protein(s) on the chromosomes. For EBV, the cellular protein EBP2 can serve to attach EBNA1 to mitotic chromosomes. During cell division, the chromosome-bound viral episomes and viral proteins are delivered to the daughter cells along with the cellular chromosomes.

Citation: Frappier L. 2004. Viral Plasmids in Mammalian Cells, p 325-340. In Funnell B, Phillips G (ed), Plasmid Biology. ASM Press, Washington, DC. doi: 10.1128/9781555817732.ch15
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Image of Figure 4
Figure 4

The BPV origin of replication and its activation. (A) Organization of the BPV origin showing binding sites for El (E1BS) and E2 (E2BS). (B) Schematic representation of El and E2 loading on the BPV minimal origin according to Sanders and Stenlund (110). Arrows indicate the 18-bp palindromic El-binding sequence.

Citation: Frappier L. 2004. Viral Plasmids in Mammalian Cells, p 325-340. In Funnell B, Phillips G (ed), Plasmid Biology. ASM Press, Washington, DC. doi: 10.1128/9781555817732.ch15
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References

/content/book/10.1128/9781555817732.chap15
1. Adams, A. 1987. Replication of latent Epstein-Barr virus genomes. J. Virol. 61:17431746.
2. Ambinder, R. F.,, M. Mullen,. Y. Chang,, G. S. Hayward,, and S. D. Hayward. 1991. Functional domains of Epstein-Barr nuclear antigen EBNA-1 J. Virol. 65:14661478.
3. Ambinder, R. F.,, W. A. Shah,, D. R. Rawlins,, G. S. Hayward,, and S. D. Hayward. 1990. Definition of the sequence requirements for binding of the EBNA-1 protein to its palindromic target sites in Epstein-Barr virus DNA. J. Virol. 64:23692379.
4. Avolio-Hunter, T. M., and L. Frappier. 1998, Mechanistic studies on the DNA linking activity of the Epstein-Barr nuclear antigen 1. Nucleic Acids Res. 26:4462-–4470.
5. Avolio-Hunter, T. M.,, P. N. Lewis,, and L. Frappier. 2001. Epstein-Barr nuclear antigen 1 binds and destabilizes nucleosomes at the viral origin of latent DNA replication. Nucleic Acids Res. 29:35203528.
6. Babcock, G. J.,, D. Hochberg,, and 1). A. Thorley-Lawson. 2000. The expression pattern of Epstein-Barr virus latent genes in vivo is dependent upon the differentiation stage of the infected B cell. Immunity 13:497506.
7. Ballestas, M. E.,, P. A. Chads,, and K. M. Kaye. 1999. Efficient persistence of extrachromosomal KSHV DNA mediated by latency-associated nuclear antigen. Science 284:641644.
8. Ballestas, M. E.,, and K. M. Kaye. 2001. Kaposi's sarcoma-associated herpesvirus latency-associated nuclear antigen 1 mediates episome persistence through W.s-acting terminal repeat (TR) sequence and specifically binds TR DNA. J. Virol 75:32503258.
9. Bashaw, J. M.,, and J. L. Yates. 2001. Replication from oriP of Epstein-Barr virus requires exact spacing of two bound dimers of EBNA1 which bend DNA. J. Virol. 75:1060310611.
10. Batien, N.,, and A. A. McBride. 2000. Interaction of the papillomavirus E2 protein with mitotic chromosomes. Virology 270:124134.
11. Berg, M.,, and A. Stenlund. 1997. Functional interactions between papiloomavirus E1 and E2 proteins. J. Virol. 71:38533863.
12. Blitz, I. L.,, and L. A. Laimins. 1991. The 68-kilodalton E1 protein of bovine papillomavirus is a DNA-binding phosphoprotein which associates with the E2 transcriptional activator in vitro. J. Virol. 65:649656.
13. Bochkarev, A.,, J. Barwell,. R. Pfuetzner,, E. Bochkareva,, L. Frappier,, and A. M. Edwards. 1996. Crystal structure of the DNA-binding domain of the Epstein-Barr virus origin binding protein, EBNA1, bound to DNA. Cell 84:791800.
14. Bochkarev, A.,, J. Barwell,, R. Pfuetzner,, W. Furey,, A. Edwards,, and L. Frappier. 1995. Crystal structure of the DNA-binding domain of the Epstein-Barr virus origin binding protein EBNA1. Cell 83:3946.
15. Bochkarev, A.,, E. Bochkareva,, L. Frappier,, and A. M. Edwards. 1998. 2.2A structure of a permanganate-sensitive DNA site bound by the Epstein-Barr virus origin binding protein, EBNA I, J. Mol. Biol. 284:12731278.
16. Bonne-Andrea, C.,, S. Santucci,, and P. Clerant. 1995. Bovine papillomavirus E1 protein can, by itself, efficiently drive multiple rounds of DNA synthesis in vitro. J. Virol. 69:32013205.
17. Ceccarelli, D. F. J.,, and L. Frappier. 2000. Functional analyses of the EBNA1 origin DNA-binding protein of Epstein- Barr virus. J Virol. 74:49394948.
18. Chaudhuri, B.,, H. Xu,, I. Todorov,, A. Dutta,, and J. L. Yates. 2001. Human DNA replication initiation factors, ORC and MCM, associate with oriP of Epstein-Barr virus. Proc. Natl Acad. Sci. USA 98:1008510089.
19. Chen, G.,, and A. Stenlund. 1998. Characterization of the DNA-binding domain of the bovine papillomavirus replication initiator E1. J. Virol. 72:25672576.
20. Chen, G.,, and A. Stenlund. 2001. The E1 initiator recognizes multiple overlapping sites in the papillomavirus origin of DNA replication. J. Virol. 75:292302.
21. Chen, G.,, and A. Stenlund. 2000. Two patches of amino acids on the E2 DNA-binding domain define the surface for interaction with E1. J. Virol. 74:15061512.
22. Chen, M.-R.,, J. M. Middeldorp,, and S. D. Hayward, 1993, Separation of the complex DNA-binding domain of EBNA-1 into DNA recognition and dimerization subdomains of novel structure. J. Virol. 67:48754885.
23. Chittenden, T.,, S. Lupton,, and A. J. Levine. 1989. Functional limits of oriP, the Epstein-Barr virus plasmid origin of replication. J. Virol. 63:30163025.
24. Cole, C. N.,, and S. D. Conzen,. 2001. Polyomaviridae: The viruses and their replicarion, p. 21412174. In D. M. Knipe, and P. M. Howley (ed.), Fields Virology, vol. 2, Lippincott Williams and Wilkins, Philadelphia, Pa..
25. Collins, C. M.,, and P. G. Medveczky. 2002. Genetic requirements for the episomal maintenance of oncogenic herpesvirus genomes. Adv. Cancer Res. 84:155174.
26. Cotter, M. A.,, and E. S. Robertson. 1999, The latency-associated nuclear antigen tethers the Kaposi's sarcoma-associated herpesvirus genome to host genomes to host chromosomes in body cavity-based lymphoma cells. Virology. 264:254264.
27. Cruickshank, J.,, A. Davidson,, A. M. Edwards,, and L. Frappier. 2000. Two domains of the Epstein-Barr virus origin DNA-binding protein, EBNA1, orchestrate sequence-specific DNA-binding. J. Biol. Chem. 275:2227322277.
28. Delecluse, H.-J.,, S. Bartnizke,, W. Hammerschmidt,, J . Bullerdick,, and G. W. Bornkamm. 1993. Episomal and integrated copies of Epstein-Barr virus coexist in Burkitt's lymphoma cell lines. J. Virol. 67:12921299.
29. Deng, Z.,, L. Lezina,, C.-J. Chen,, S. Shtivelband,, W. So,, and P. M. Lieberman. 2002. Telomeric proteins regulate episomal maintenance of Epstein-Barr virus origin of plasmid replication. Mol. Cell 9:493503.
30. DePamphilis, M. L. 1993. Eukaryotic DNA replication: anatomy of an origin. Annu. Rev. Biochem. 62:2963.
31. Dhar, S. K.,, K. Yoshida,, Y. Machida,, P. Khaira,, B. Chaudhuri,, J. A. Wohlschlegel,, M. Leffak,, J. Yates,, and A. Dutta. 2001. Replication from oriP of Epstein-Barr virus requires human ORC and is inhibited by geminin. Cell 106:287296.
32. Dhar, V.,, and C. L. Schildkraut. 1991. Role of EBNA-1 in arresting replication forks at the Epstein-Barr virus oriP family of tandem repeats. Mol. Cell. Biol. 11:62686278.
33. Dostatni, N.,, F. Thierry,, and M. Yaniv. 1988. A dimer of BPV-1 E2 containing a protease resistant core interacts with its DNA target. EMBO J. 7:38073816.
34. Edwards, A. M.,, A. Bochkarev,, and L. Frappier. 1998. Origin DNA-binding proteins. Curr. Opin. Struct. Biol. 8:4953.
35. Enemark, E. J.,, G. Chen,, D. E. Vaughn,, A. Stenlund,, and L. Joshua-Tor, 2000. Crystal structure of the DNA-binding domain of the replication initiation protein E1 from papillomavirus. Mol. Cell 6:149158.
36. Enemark, E. J.,, A. Stenlund,, and L. Joshua-Tor, 2002. Crystal structure of two intermediates in the assembly of the papillomavirus replication initiation complex. EMBO J. 21:14871496.
37. Ermakova, O.,, L. Frappier,, and C. L. Schildkraut. 1996. Role of the EBNA-1 protein in pausing of replication forks in the Epstein-Barr virus genome. J. Biol. Chem. 271:3300933017.
38. Frappier, L.,, K. Goldsmith,, and L. Bendell. 1994. Stabilization of the EBNA1 protein on the Epstein-Barr virus latent origin of DNA replication by a DNA looping mechanism. J. Biol. Chem. 269:10571062.
39. Frappier, L.,, and M. O'Donnell. 1992. EBNA I distorts oriP, the Epstein-Barr virus latent replication origin. J. Virol. 66:17861790.
40. Frappier, L.,, and M. O'Donnell 1991. Epstein-Barr nuclear antigen 1 mediates a DNA loop within the latent replication origin of Epstein-Barr virus. Proc. Natl. Acad. Sci. USA 88:1087510879.
41. Frappier, L.,, and M. O'Donnell. 1991. Overproduction, purification and characterization of EBNA1, the origin binding protein of Epstein-Barr virus. J. Biol. Chem. 266:78197826.
42. Gahn, T. A.,, and C. L. Schildkraut. 1989. The Epstein-Barr virus origin of plasmid replication, oriP, contains both the initiation and termination sites of DNA replication. Cell 58:527535.
43. Garber, A. C.,, J. Hu,, and R. Renne. 2002. Latency-associated nuclear antigen (LANA) cooperatively binds to two sites within the terminal repeat, and both sites contribute to the ability of LANA to suppress transcription and to facilitate DNA replication. J. Biol. Chem. 277:2740127411.
44. Garber, A. C.,, M. A. Shu,, J. Hu,, and R. Renne. 2001. DNA-binding and modulation of gene expression by the latency-associated nuclear antigen of Kaposi's sarcoma-associated herpesvirus. J. Virol. 75:78827892.
45. Gilbert, D. M.,, and S. N. Cohen. 1987. Bovine papilloma virus plasmids replicate randomly in mouse fibroblasts throughout S phase of the cell cycle. Cell 50:5968.
46. Gillette, T. G.,, and J. A. Borowiec, 1998. Distinct roles of two binding sites for the bovine papillomavirus (BPV) E2 transactivator on BPV DNA replication. J. Virol. 72:57355744.
47. Gillette, T. G.,, M. Lusky,, and J. A. Boroweic. 1994. Induction of structural changes in the bovine papillomavirus type 1 origin of DNA replication by the viral E1 and E2 proteins. Proc. Natl. Acad. Sci. USA 91:88468850.
48. Gillitzer, E.,, G. Chen,, and A. Stenlund. 2000. Separate domains in E1 and E2 proteins serve architectural and productive roles for cooperative DNA-binding. EMBO J. 19: 30693079.
49. Goldsmith, K.,, L. Bendell,, and L. Frappier. 1993. Identification of EBNA1 amino acid sequences required for the interaction of the functional elements of the Epstein-Barr vims latent origin of DNA replication. J. Virol. 67:34183426.
50. Grogan, E. A.,, W. P. Summers,, S. Dowling,, D. Shedd,, L. Gradoville,, and G. Miller. 1983. Two Epstein-Barr viral nuclear neoantigens distinguished by gene transfer, serology and chromosome binding. Proc. Natl. Acad. Sci. USA 80:76507653.
51. Hammerschmidt, W.,, and B. Sugden. 1988. Identification and characterization of oriLyt, a lytc origin of DNA replication of Epstein-Barr virus. Cell 55:427433.
52. Han, Y.,, Y.-M. Loo,, K. T. Militello,, and T. Melendy. 1999, Interactions of the papovavirus DNA replication initiator proteins, bovine papillomavirus type 1 E1 and simian virus 40 large T antigen with human replication protein A. J. Virol. 73:48994907.
53. Harris, A.,, B. D. Young,, and B. E. Griffin. 1985. Random association of Epstein-Barr virus genomes with host cell metaphase chromosomes in Burkitt's lymphoma-derived cell lines. J. Virol. 56:328332.
54. Harrison, S.,, K. Fisenne,, and J. Hearing. 1994. Sequence requirements of the Epstein-Barr virus latent origin of DNA replication. J. Virol 68:19131925.
55. Hassell, J. A.,, and B. T. Brinton,. 1996. SV40 and polyoma DNA replication, p. 639678. In M. L. DePamphilis (ed.), DNA Replication in Eukaryotic Cells. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y..
56. Hearing, J.,, Y. Mulhaupt,, and S. Harper. 1992, Interaction of Epstein-Barr virus nuclear antigen 1 with the viral latent origin of replication. J. Virol. 66:694705.
57. Hegde, R. S.,, S. R. Grossman,, L. A. Laimins,, and P. B. Sigler. 1992. Crystal structure at 1.7A of the bovine papillomavirus-! E2 DNA-binding protein bound to its DNA target. Nature 359:505512.
58. Hieter, P.,, C. Mann,, M. Snyder,, and R. W. Davis. 1985, Mitotic stability of yeast chromosomes: a colony color assay that measures nondisjunction and chromosome loss. Cell 40:381392.
59. Holt, S. E.,, G. Schuller,, and V. G. Wilson. 1994. DNA-binding specificity of the bovine papillomavirus E1 protein is determined by sequence contained within an 18-base-pair inverted repeat element at the origin of replication. J. Virol 68:10941102.
60. Howley, P. M., and D. R. Lowy,. 2001. Papillomaviruses and their replication, p. 21972230. In D. M. Knipe, and P. M. Howley (ed.), Fields Virology, vol. 2. Lippincott Williams and Wilkins, Philadelphia, Pa..
61. Hsieh, D.-J.,, S. M. Camiolo,, and J. L. Yates. 1993. Constitutive binding of EBNA1 protein to the Epstein-Barr virus replication origin, oriP, with distortion of DNA structure during latent infection. EMBO J. 12:49334944.
62. Hu, J.,, A. C. Garber,, and R. Renne. 2002. The latency-associated nuclear antigen of Kaposi's sarcoma-associated herpesvirus supports latent DNA replication in dividing cells. J. Virol. 76:11167711687.
63. Hung, S. C.,, M.-S. Kang,, and E. Kieff. 2001. Maintenance of Epstein-Barr virus (EBV) oriP-bascd episomes requires EBV-encoded nuclear antigen-1 chromosome-binding domains, which can be replaced by high-mobility group-I or histone H1. Proc. Natl. Acad. Sci. USA 98:18651870.
64. Ilves, L.,, S. Kivi,, and M. Ustav. 1999. Long-term episomal maintenance of bovine papillomavirus type 1 plasmids is determined by attachment to host chromosomes, which is mediated by the viral E2 protein and its binding sites. J. Virol. 73:44044412.
65. Ishimi, Y. 1997. A DNA helicase activity is associated with an MCM4,-6,-7 protein complex. J. Biol. Chem. 272:2450824513.
66.. Jankelevich, S.,, J. L. Kolman,, J. W. Bodnar,, and G. Miller. 1992. A nuclear matrix attachment region organizes the Epstein-Barr viral plasmid in Raji cells into a single DNA domain. EMBO J. 11:11651176.
67. Joseph, A. M.,, G. J. Babcock,, and D. A. Thorley-Lawson. 2000. Cells expressing the Epstein-Barr virus growth program are present in and restricted to the naive B-cell subset of healthy tonsils. J. Virol. 74:99649971.
68. Kanda, T.,, M. Otter,, and G. M. Wahl. 2001. Coupling of mitotic chromosome tethering and replication competence in Epstein- Barr virus-based plasmids. Mol. Cell. Biol. 21:35763588.
68.a. Kapoor, P.,, and L. Frappier. 2003. EBNA1 partitions Epstein-Barr virus plasmids in yeast cells by attaching to human EBNA1-binding protein 2 on mitotic chromosomes. J. Virol. 77:69466956.
69. Kapoor, P.,, K. Shire,, and L. Frappier. 2001. Reconstitution of Epstein-Barr virus-based plasmid partitioning in budding yeast. EMBO J. 20:222230.
70. Kim, A, L.,, M, Maher,, J. B. Hayman,. J. Ozer,, D. Zerby,, J. L. Yates,, and P. M. Lieberman. 1997. An imperfect correlation between DNA replication activity of Epstein- Barr virus nuclear antigen 1 (EBNA1) and binding to the nuclear import receptor, Rch1/importin α. Virology 239:340351.
71. Kirchmaier, A. L.,, and B. Sugden. 1997, Dominant-negative inhibitors of EBNA1 of Epstein-Barr virus. J. Virol. 71:17661775.
72. Kirchmaier, A. L.,, and B. Sugden. 1995. Plasmid maintenance of derivatives of oriP of Epstein-Barr virus. J. Virol. 69:12801283.
73. Kirchmaier, A. L.,, and B. Sugden. 1998. Rep*: a viral element that can partially replace the origin of plasmid DNA synthesis of Epstein-Barr virus. J. Virol. 72:46574666.
74. Klein, G. 1989. Viral latency and transformation: the strategy of Epstein-Barr virus. Cell 58:58.
75. Koons, M. D.,, S. Van Scoy,, and J. Hearing. 2001. The replicator of the Epstein-Barr virus latent cycle origin of DNA replication, oriP is composed of multiple functional elements. J. Virol. 75:1058210592.
76. Krithivas, A.,, M. Fujimuro,, M. Weidner,, D. B. Young,, and S. D. Hayward. 2002. Protein interactions targeting the latency-associated nuclear antigen of Kaposi's sarcoma-associated herpesvirus to cell chromosomes. J. Virol. 76:1159611604.
77. Krysan, P. J.,, S. B. Haase,, and M. P. Calos. 1989. Isolation of human sequences that replicate autonomously in human cells. Mol. Cell. Biol. 9:10261033.
78. Laine, A.,, and L. Frappier. 1995. Identification of Epstein- Barr nuclear antigen 1 protein domains that direct interactions at a distance between DNA-bound proteins. J. Biol Chem. 270:3091430918.
79. Langle-Rouault, F.,, V. Patzel,, A. Benavente,, M. Taillez,, N. Silvestre,, A. Bompard,, G. Sczakiel,, E. Jacobs,, and K. Rittner. 1998. Up to 100-fold increase of apparent gene expression in the presence of Epstein-Barr virus oriP sequences and EBNA1: implications of the nuclear import of plasmids. J. Virol. 72:61816185.
80. Lehman, C. W.,, and M. R. Botchan. 1998. Segregation of viral plasmids depends on tethering to chromosomes and is regulated by phosphorylation. Proc. Natl. Acad. Sci. USA 95:43381343.
81. Leight, E. R.,, and B. Sugden. 2001. The cis-acting family of repeats can inhibit as well as stimulate establishment of an oriP replicon. J. Virol. 75:1070910720.
82. Li, R.,, and M. R. Botchan. 1994. Acidic transcription factors alleviate nucleosome-mediated repression of DNA replication of bovine papillomavirus type 1. Proc. Natl. Acad. Sci. USA 91:70517055.
83. Li, R.,, and M. R. Botchan. 1993. The acidic transcriptional activation domains of VP 16 and p53 bind the cellular replication protein A and stimulate in vitro BPV-1 DNA replication. Ce1l 73:12071221.
84. Little, R. D.,, and C. L. Schildkraut. 1995. Initiation of latent DNA replication in the Epstein-Barr virus genome can occur at sites other than the genetically defined origin. Mol. Cell. Biol. 15:28932903.
85. Lupton, S.,, and A. J. Levine. 1985. Mapping of genetic elements of Epstein-Barr virus that facilitate extrachromosomal persistence of Epstein-Barr virus-derived plasmids in human cells. Mol. Cell. Biol. 5:25332542.
86. Mackey, D.,, T. Middleton,, and B. Sugden. 1995. Multiple regions within EBNA 1 can link DNAs. J. Virol. 69:61996208.
87. Mackey, D.,, and B. Sugden. 1999. The linking regions of EBNA1 are essential for its support of replication and transcription. Mol. Cell. Biol. 19:33493359.
88. Marechal, V.,, A. Dehee,, R. Chikhi-Brachet,, T. Piolot,, M. Coppey-Moisan,, and J. Nicolas. 1999, Mapping EBNA1 domains involved in binding to metaphase chromosomes. J. Virol. 73:43854392.
89. McBride, A. A.,, R. Schlegel,, and P. M. Howley. 1988. The carboxy-terminal domain shared by the bovine papillomavirus E2 transactivator and repressor proteins contains a specific DNA-binding activity. EMBO J. 7:533539.
90. Melendy, T.,, J. Sedman,, and A. Stenlund. 1995. Cellular factors required for papillomavirus DNA replication. J. Virol. 69:78577867.
91. Mendez, J.,, and B. Stillman. 2000. Chromatin association of human origin recognition coplex, cdc6, and minichromosome maintenance proteins during the cell cycle: assembly of prereplication complexes in late mitosis. Mol. Cell. Biol. 20:86028612.
92. Mendoza, R.,, L. Ganhhi,, and M. R. Botchan. 1995. E1 recognition sequences in the bovine papillomavirus type 1 origin of DNA replication: interaction between half sites of the inverted repeats. J. Virol. 69:37893798.
93. Middleton, T.,, and B. Sugden. 1992. EBNA1 can link the enhancer element to the initiator element of the Epstein-Barr virus plasmid origin of DNA replication. J. Virol. 66:489495.
94. Miyashita, E., M. B. Yang,, G. J. Babcock,, and D. A. Thorley- Lawson. 1997. Identification of the site of Epstein-Barr virus persistence in vivo as a resting B cell. J. Virol. 71:48824891.
95. Mohr, I.,, R. Clark,, S. Sun,, E. J. Androphy,, P. MacPherson,, and M. R. Botchan. 1990. Targeting the E1 replication protein to the papillomavirus origin of replication by complex formation with the E2 transactivator. Science 250:16941699.
96. Niller, H. H., G. Glaser,, R. Knuchel,, and H. Wolf. 1995. Nucleoprotein complexes and DNA 5'-ends at oriP of Epstein- Barr virus. J. Biol. Chem. 270:1286412868.
97. Norio, P., and C. L. Schildkraut. 2001. Visualization of DNA replication on individual Epstein-Barr virus episomes. Science 294:23612364.
98. Norio, P.,, C. L. Schildkraut,, and J. L. Yates. 2000. Initiation of DNA replication within oriP is dispensable for stable replication of the latent Epstein-Barr virus chromosome after infection of established cell lines. J. Virol. 74:85638574.
99. Park, P.,, W. Copeland,, L. Yang,, T. Wang,, M. R. Botchan,, and I. J. Mohr. 1994. The cellular DNA polymerase α-primase is required for papillomavirus DNA replication and associates with the viral E1 helicase. Proc. Natl. Acad. Sci. USA 91:87008704.
100. Pepinsky, R. B.,, S. S. Prakash,, K. Corina,, M. J. Grossel,, J. Barsoum,, and E. J. Androphy. 1997. Sequences flanking the core DNA-binding domain of bovine papillomavirus type 1 E2 contribute to DNA-binding function. J. Virol. 71:828831.
101. Petti, L.,, C. Sample,, and E. Kieff. 1990. Subnuclear localization and phosphorylation of Epstein-Barr virus latent infection nuclear proteins. Virology 176:563574.
102. Piirsoo, M.,, E. Ustav,, T. Mandel,, A. Stenlund,, and M. Ustav. 1996. Cis and trans requirements for stable episomal maintenance of the BPV-1 replicator. EMBO J. 15:111.
103. Piolot, T.,, M. Tramier,, M. Coppey,, J.-C. Nicolas,, and V. Marechal. 2001. Close but distinct regions of human herpesvirus 8 latency-associated nuclear antigen 1 are responsible for nuclear targeting and binding to human mitotic chromosomes. J. Virol. 75:39483959.
104. Polvino-Bodnar, M.,, and P. A. Schaffer. 1992. DNA-binding activity is required for EBNA1 -dependent transcriptional activation and DNA replication. Virology 187:591603.
105. Rawlins, D. R.,, G. Milman,, S. D. Hayward,, and G. S. Hayward. 1985. Sequence-specific DNA-binding of the Epstein-Barr virus nuclear antigen (EBNA1) to clustered sites in the plasmid maintenance region. Cell 42:859868.
106. Reisman, D.,, and B. Sugden. 1986. trans Activation of an Epstein-Barr viral transcripitonal enhancer by the Epstein- Barr viral nuclear antigen 1. Mol. Cell. Biol. 6:38383846.
107. Reisman, D.,, J. Yates,, and B. Sugden. 1985. A putative origin of replication of plasmids derived from Epstein-Barr virus is composed of two as-acting components. Mol. Cell. Biol. 5:18221832.
108. Rialland, M.,, F. Sola,, and C. Santocanale. 2002. Essential role of human CDT1 in DNA replication and chromatin licensing. J. Cell Sci. 115:14351440.
109. Rozenberg, H.,, D. Rabinovich,, F. Frolow,, R. S. Hegde,, and Z. Shakked. 1998. Structural code for DNA recognition revealed in crystal structures of papillomavirus E2-DNA targets. Proc. Natl. Acad. Sci. USA 95:1519415199.
110. Sanders, C. M.,, and A. Stenlund. 1998. Recruitment and loading of the E1 initiator protein: an ATP-dependent process catalysed by a transcription factor. EMBO J. 17:70447055.
111. Schepers, A.,, M. Ritzi,, K. Bousset,, E. Kremmer,, J. L. Yates,, J. Harwood,, J. F. X. Diffley,, and W. Hammerschmidt. 2001. Human origin recognition complex binds to the region of the latent origin of DNA replication of Epstein-Barr virus. EMBO J. 20:45884602.
112. Schwam, D. R.,, R. L. Luciano,, S. S. Mahajan,, L. Wong,, and A. C. Wilson. 2000. Carboxy terminus of human herpesvirus 8 latency-associated nuclear antigen mediates dimerization, transcriptional repression, and targeting to nuclear bodies. J. Virol. 74:85328540.
113. Sedman, J.,, and A. Stenlund. 1995. Co-operative interaction between the initiator E1 and the transcriptional activator E2 is required for replicator specific DNA replication of bovine papillomavirus in vivo and in vitro. EMBO J. 14:62186228.
114. Sco, Y.-S.,, F. Muller,, M. Lusky,, E. Gibbs,, H.-Y. Kim,, B. Phillips,, and J. Hurwitz. 1993. Bovine papilloma virus (BPV)-encoded E2 protein enhances binding of E1 protein to the BPV replication origin, Proc. Nat. Acad. Sci. USA 90:28652869.
115. Seo, Y.-S.,, F. Muller,, M. Lusky,, and J. Hurwitz. 1993. Bovine papilloma virus (BPV)-encoded E1 protein contains multiple activities required for BPV replication. Proc. Natl. Acad. Sci. USA 90:702706.
116. Shaw, J.,, L. Levinger,, and C. Carter. 1979. Nucleosomal structure of Epstein-Barr virus DNA in transformed cell lines, J. Virol. 29:657665.
117. Shirakata, M.,, K.-I. Imadome,, and K. Hirai. 1999. Requirement of replication licensing for the dyad symmetry element- dependent replication of the Epstein-Barr virus oriP minichromosome. Virology 263:4254.
118. Shirakata, M.,, K. -L Imadome,, K. Okazaki,, and K. Hirai. 2001. Activation of TRAF5 and TRAF6 signal cascades negatively regulates the latent replication origin of Epstein-Barr virus through p38 mitogen-activated protein kinase. J. Virol. 75:50595068.
119. Shire, K.,, D. F. J . Ceccarelli,, T. M. Avolio-Hunter,, and L. Frappier. 1999. EBP2, a human protein that interacts with sequences of the Epstein-Barr nuclear antigen 1 important for plasmid maintenance. J. Virol. 73:25872595.
120. Simpson, K.,, A. McGuigan, and C Huxley. 1996. Stable episomal maintenance of yeast artificial chromosomes in human cells. Mol. Cell. Biol. 16:51175126.
121. Skiadopoulos, M. H.,, and A. A. McBride. 1998. Bovine papillomavirus type 1 genomes and the E2 transactivator protein are closely associated with mitotic chromatin. J. Virol 72:20792088.
122. Sternas, L.,, T. Middleton,, and B. Sugden. 1990. The average number of molecules of Epstein-Barr nuclear antigen 1 per cell does not correlate with the average number of Epstein- Barr virus (EBV) DNA molecules per cell among different clones of EBV-immortalized cells. J. Virol. 64:24072410.
123. Su, W.,, T. Middleton,, B. Sugden,, and H. Echols. 1991. DNA looping between the origin of replication of Epstein-Barr virus and its enhancer site: stabilization of an origin complex with Epstein-Barr nuclear antigen I. Proc. Natl. Acad Sci. USA 88:1087010874.
124. Summers. H.,, J. A. Barwell,, R. A. Pfuetzner,, A. M. Edwards,, and L. Frappier. 1996. Cooperative assembly of EBNA1 on the Epstein-Barr virus latent origin of replication. J. Virol. 70:12281231.
125. Summers, H.,, A. Fleming,, and L. Frappier. 1997. Requirements for EBNA I-induced permanganate sensitivity of the Epstein-Barr virus latent origin of DNA replication. J. Biol Chem. 272:2643426440.
126. Szekely, L.,, C. Kiss,, K. Mattson,, E. Kashuba,, K. Pokrovskaja,, A. Juhasz,, P. Holmvall,, and G. Klein. 1999. Human herpesvirus- 8-encoded LNA-I accumulates in heterchromatin-associated nuclear bodies. J. Gen. Virol. 80:28892900.
127. Thorley-Lawson, D. A.,, E. M. Miyashita,, and G. Khan. 1996. Epstein-Barr virus and the B cell: that's all it takes. Trends Microbiol. 4:204208.
128. Thorner, L. K.,, D. A. Lim,, and M. R. Botchan. 1993. DNA-binding domain of bovine papillomavirus type 1 E1 helicase: structural and functional aspects. J. Virol. 67:60006014.
129. Tierney, R. J.,, N. Steven,, L. S. Young,, and A. B. Rickinson. 1994. Epstein-Barr virus latency in blood mononuclear cells: analysis of viral gene transcription during primary infection and in the carrier state. J. Virol. 68:73747385.
130. Ustav, E.,, M. Ustav,, P. Szymanski,, and A. Stenlund. 1993. The bovine papillomavirus origin of replication requires a binding site for the E2 transcriptional activator. Proc. Natl. Acad. Sci. USA 90:898902.
131. Ustav, M.,, and A. Stenlund. 1991. Transient replication of BPV-1 requires two viral polypeptides encoded by the E1 and E2 open reading frames. EMBO J. 10:449457.
132. Ustav, M.,, E. Ustav,, P. Szymanski,, and A. Stenlund. 1991. Identification of the origin of replication of the bovine papillomavirus and characterization of the viral origin recognition factor E1 . EMBO J. 10:43214329.
133. Van Scoy, S.,, I. Watakabe,, A. R, Krainer, and J. Hearing. 2000. Human p32: a coactivator for Epstein-Barr virus nuclear antigen-1-mediated transcriptional activation and possible role in viral latent cycle DNA replication. Virology 275:145157.
134. Vogel, M.,, K. Wittmann,, E. Endl,, G. Glaser,, R. Knuchel, H, Wolf, and H. H. Niller. 1998. Plasmid maintenance assay based on green fluorescent protein and FACS of mammalian cells. BioTechniques 24:540544.
135.. Voitenleitner, C.,, and M. Botchan. 2002. E1 protein of bovine papiloomavirus type 1 interferes with E2 protein-mediated tethering of the viral DNA to mitotic chromosomes. J. Virol. 76:34403451.
136. Wendelburg, B.,, and J.-M. Vos. 1998. An enhanced EBNA1 variant with reduced IR3 domain for long-term episomal maintenance and transgene expression of or/P-based plasmids in human cells. Gene Ther. 5:13891399.
137. White, R. E.,, R. Wade-Martin,, and M. R. James. 2001. Sequences adjacent to oriP improve the persistence of Epstein- Barr virus-based episomes in B cells. J. Virol. 75:1124911252.
138. Wu, H.,, D. F. J. Ceccarelli,, and L. Frappier. 2000. The DNA segregation mechanism of the Epstein-Barr virus EBNA I protein. EMBO Rep. 1:140144.
139. Wu, H.,, P. Kapoor,, and L. Frappier. 2002. Separation of the DNA replication, segregation and transcriptional activation functions of Epstein-Barr nuclear antigen 1. J. Virol. 76:24802490.
140. Wysokenski, D. A.,, and J. L. Yates. 1989. Multiple EBNA1-binding sites arc required to form an EBNA 1-dependent enhancer and to activate a minimal replicative origin within oriP of Epstein-Barr virus. J. Virol. 63:26572666.
141. Yang, L.,, and M. Botchan. 1990. Replication of bovine papillomavirus type 1 DNA initiates within an E2-responsive enhancer element. J. Virol 64:59035911.
142. Yang, L.,, E. Fouts,, D. A., Lim,, M., Nohaile,, and M. Botchan. 1993. The E1 protein of bovine papilloma virus 1 is an ATP-dependent DNA helicase. Proc. Natl. Acad. Sci. USA 90:50865090.
143. Yates, J. L.,, and S. M. Camiolo. 1988. Dissection of DNA replication and enhancer activation functions of Epstein-Barr virus nuclear antigen 1. Cancer Cells 6:197205.
144. Yates, J. L.,, S. M. Camiolo,, and J. M. Bashaw. 2000. The minimal replicator of Epstein-Barr virus oriP. J. Virol. 74:45124522.
145. Yates, J. L.,, and N. Guan. 1991. Epstein-Barr virus-derived plasmids replicate only once per cell cycle and arc not amplified after entry into cells. J. Virol. 65:483488.
146. Yates, J. L.,, N. Warren,, D. Reisman,, and B. Sugden. 1984. 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. USA 81:38063810.
147. Yates, J. L.,, N. Warren,, and B. Sugden. 1985. Stable replication of plasmids derived from Epstein-Barr virus in various mammalian cells. Nature 313:812815.
148. Zhang, D.,, L. Frappier,, E. Gibbs,, J. Hurwitz,, and M. O'Donnell. 1998. Human RPA (hSSB) interacts with EBNA1, the latent origin binding protein of Epstein-Barr virus. Nucleic Acids Res. 26:631637.

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