Kaposi's sarcoma herpesvirus genome persistence

Frontiers in Microbiology

Volumn 7, Issue AUG, 2016, Pages

  Juillard, Franceline ^a   Tan, Min ^a   Li, Shijun ^a   Kaye, Kenneth M ^a  

^a BRIGHAM AND WOMEN S HOSPITAL   (United States)

Author keywords

Chromosome; DNA binding; KSHV; Latency associated nuclear antigen; Viral persistence

Indexed keywords

CYCLIN DEPENDENT KINASE; EXTRACHROMOSOMAL DNA; FLICE INHIBITORY PROTEIN; HISTONE H2A; HISTONE H2B; HISTONE METHYLTRANSFERASE; LATENCY ASSOCIATED NUCLEAR ANTIGEN; NICOTINAMIDE ADENINE DINUCLEOTIDE ADENOSINE DIPHOSPHATE RIBOSYLTRANSFERASE 1; REPLICATION FACTOR C;

B CELL LYMPHOMA; BACTERIAL ARTIFICIAL CHROMOSOME; DNA REPLICATION; DNA SEQUENCE; EPIGENETICS; GEL MOBILITY SHIFT ASSAY; HUMAN; HUMAN HERPESVIRUS 8; IMMUNOFLUORESCENCE; KAPOSI SARCOMA; LATENT VIRUS INFECTION; NONHUMAN; PERSISTENT VIRUS INFECTION; PRIMARY EFFUSION LYMPHOMA; PROTEIN PROCESSING; REVIEW; TRANSCRIPTION REGULATION; VIRAL GENETICS; WART VIRUS; X RAY CRYSTALLOGRAPHY;

EID: 84988884569     PISSN: None     EISSN: 1664302X     Source Type: Journal    
DOI: 10.3389/fmicb.2016.01149     Document Type: Review

References (115)

1. Alkharsah, K. R., and Schulz, T. F. (2012). A role for the internal repeat of the Kaposi's sarcoma-associated herpesvirus latent nuclear antigen in the persistence of an episomal viral genome. J. Virol. 86, 1883-1887. doi: 10.1128/JVI.06029-11
2. Bajaj, B. G., Verma, S. C., Lan, K., Cotter, M. A., Woodman, Z. L., and Robertson, E. S. (2006). KSHV encoded LANA upregulates Pim-1 and is a substrate for its kinase activity. Virology 351, 18-28. doi: 10.1016/j.virol.2006.03.037
3. Ballestas, M. E., Chatis, P. A., and Kaye, K. M. (1999). Efficient persistence of extrachromosomal KSHV DNA mediated by latency-associated nuclear antigen. Science 284, 641-644. doi: 10.1126/science.284.5414.641
4. Ballestas, M. E., and Kaye, K. M. (2001). Kaposi's sarcoma-associated herpesvirus latency-associated nuclear antigen 1 mediates episome persistence through cis-acting terminal repeat (TR) sequence and specifically binds TR DNA. J. Virol. 75, 3250-3258. doi: 10.1128/JVI.75.7.3250-3258.2001
5. Barbera, A. J., Ballestas, M. E., and Kaye, K. M. (2004). The Kaposi's sarcoma-associated herpesvirus latency-associated nuclear antigen 1 N terminus is essential for chromosome association, DNA replication, and episome persistence. J. Virol. 78, 294-301. doi: 10.1128/JVI.78.1.294-301.2004
6. Barbera, A. J., Chodaparambil, J. V., Kelley-Clarke, B., Joukov, V., Walter, J. C., Luger, K., et al. (2006a). The nucleosomal surface as a docking station for Kaposi's sarcoma herpesvirus LANA. Science 311, 856-861. doi: 10.1126/science.1120541
7. Barbera, A. J., Chodaparambil, J. V., Kelley-Clarke, B., Luger, K., and Kaye, K. M. (2006b). Kaposi's sarcoma-associated herpesvirus LANA hitches a ride on the chromosome. Cell Cycle 5, 1048-1052. doi: 10.4161/cc.5.10.2768
8. Beauchemin, C., Moerke, N. J., Faloon, P., and Kaye, K. M. (2014). Assay development and high-throughput screening for inhibitors of Kaposi's sarcoma-associated herpesvirus N-terminal latency-associated nuclear antigen binding to nucleosomes. J. Biomol. Screen. 19, 947-958. doi: 10.1177/1087057114520973
9. Bochkarev, A., Barwell, J. A., Pfuetzner, R. A., Bochkareva, E., Frappier, L., and Edwards, A. M. (1996). Crystal structure of the DNA-binding domain of the Epstein-Barr virus origin-binding protein, EBNA1, bound to DNA. Cell 84, 791-800. doi: 10.1016/S0092-8674(00)81056-9
10. Burnside, K. L., Ryan, J. T., Bielefeldt-Ohmann, H., Gregory Bruce, A., Thouless, M. E., Tsai, C. C., et al. (2006). RFHVMn ORF73 is structurally related to the KSHV ORF73 latency-associated nuclear antigen (LANA) and is expressed in retroperitoneal fibromatosis (RF) tumor cells. Virology 354, 103-115. doi: 10.1016/j.virol.2006.06.022
11. Cai, Q., Cai, S., Zhu, C., Verma, S. C., Choi, J. Y., and Robertson, E. S. (2013). A unique SUMO-2-interacting motif within LANA is essential for KSHV latency. PLoS Pathog. 9:e1003750. doi: 10.1371/journal.ppat.1003750
12. Cai, Q. L., Knight, J. S., Verma, S. C., Zald, P., and Robertson, E. S. (2006). EC5S ubiquitin complex is recruited by KSHV latent antigen LANA for degradation of the VHL and p53 tumor suppressors. PLoS Pathog. 2:e116. doi: 10.1371/journal.ppat.0020116
13. Calderwood, M. A., Hall, K. T., Matthews, D. A., and Whitehouse, A. (2004). The herpesvirus saimiri ORF73 gene product interacts with host-cell mitotic chromosomes and self-associates via its C terminus. J. Gen. Virol. 85, 147-153. doi: 10.1099/vir.0.19437-0
14. Campbell, M., Chang, P. C., Huerta, S., Izumiya, C., Davis, R., Tepper, C. G., et al. (2012). Protein arginine methyltransferase 1-directed methylation of Kaposi Sarcoma-associated herpesvirus latency-associated nuclear antigen. J. Biol. Chem. 287, 5806-5818. doi: 10.1074/jbc.M111.289496
15. Campbell, M., and Izumiya, Y. (2012). Post-translational modifications of Kaposi's sarcoma-associated herpesvirus regulatory proteins-SUMO and KSHV. Front. Microbiol. 3:31. doi: 10.3389/fmicb.2012.00031
16. Cha, S., Lim, C., Lee, J. Y., Song, Y. J., Park, J., Choe, J., et al. (2010). DNA-PK/Ku complex binds to latency-associated nuclear antigen and negatively regulates Kaposi's sarcoma-associated herpesvirus latent replication. Biochem. Biophys. Res. Commun. 394, 934-939. doi: 10.1016/j.bbrc.2010.03.086
17. Chandriani, S., and Ganem, D. (2010). Array-based transcript profiling and limiting-dilution reverse transcription-PCR analysis identify additional latent genes in Kaposi's sarcoma-associated herpesvirus. J. Virol. 84, 5565-5573. doi: 10.1128/JVI.02723-09
18. Chang, Y., Moore, P. S., Talbot, S. J., Boshoff, C. H., Zarkowska, T., Godden, K., et al. (1996). Cyclin encoded by KS herpesvirus. Nature 382, 410. doi: 10.1038/382410a0
19. Cheng, F., Weidner-Glunde, M., Varjosalo, M., Rainio, E. M., Lehtonen, A., Schulz, T. F., et al. (2009). KSHV reactivation from latency requires Pim-1 and Pim-3 kinases to inactivate the latency-associated nuclear antigen LANA. PLoS Pathog. 5:e1000324. doi: 10.1371/journal.ppat.1000324
20. Cherezova, L., Burnside, K. L., and Rose, T. M. (2011). Conservation of complex nuclear localization signals utilizing classical and non-classical nuclear import pathways in LANA homologs of KSHV and RFHV. PLoS ONE 6:e18920. doi: 10.1371/journal.pone.0018920
21. Chodaparambil, J. V., Barbera, A. J., Lu, X., Kaye, K. M., Hansen, J. C., and Luger, K. (2007). A charged and contoured surface on the nucleosome regulates chromatin compaction. Nat. Struct. Mol. Biol. 14, 1105-1107. doi: 10.1038/nsmb1334
22. Correia, B., Cerqueira, S. A., Beauchemin, C., Pires de Miranda, M., Li, S., Ponnusamy, R., et al. (2013). Crystal structure of the gamma-2 herpesvirus LANA DNA binding domain identifies charged surface residues which impact viral latency. PLoS Pathog. 9:e1003673. doi: 10.1371/journal.ppat.1003673
23. Cotter, M. A. II, and Robertson, E. S. (1999). The latency-associated nuclear antigen tethers the Kaposi's sarcoma-associated herpesvirus genome to host chromosomes in body cavity-based lymphoma cells. Virology 264, 254-264. doi: 10.1006/viro.1999.9999
24. Cotter, M. A. II, Subramanian, C., and Robertson, E. S. (2001). The Kaposi's sarcoma-associated herpesvirus latency-associated nuclear antigen binds to specific sequences at the left end of the viral genome through its carboxy-terminus. Virology 291, 241-259. doi: 10.1006/viro.2001.1202
25. De Leon Vazquez, E., Carey, V. J., and Kaye, K. M. (2013). Identification of Kshv Lana regions important for episome segregation, replication and persistence. J. Virol. 87, 12270-12283. doi: 10.1128/JVI.01243-13
26. De Leon Vazquez, E., and Kaye, K. M. (2011). The internal Kaposi's sarcoma-associated herpesvirus LANA regions exert a critical role on episome persistence. J. Virol. 85, 7622-7633. doi: 10.1128/JVI.00304-11
27. Dittmer, D., Lagunoff, M., Renne, R., Staskus, K., Haase, A., and Ganem, D. (1998). A cluster of latently expressed genes in Kaposi's sarcoma-associated herpesvirus. J. Virol. 72, 8309-8315.
28. Domsic, J. F., Chen, H. S., Lu, F., Marmorstein, R., and Lieberman, P. M. (2013). Molecular basis for oligomeric-DNA binding and episome maintenance by KSHV LANA. PLoS Pathog. 9:e1003672. doi: 10.1371/journal.ppat.1003672
29. Fejer, G., Medveczky, M. M., Horvath, E., Lane, B., Chang, Y., and Medveczky, P. G. (2003). The latency-associated nuclear antigen of Kaposi's sarcoma-associated herpesvirus interacts preferentially with the terminal repeats of the genome in vivo and this complex is sufficient for episomal DNA replication. J. Gen. Virol. 84, 1451-1462. doi: 10.1099/vir.0.18940-0
30. Forrest, J. C., Paden, C. R., Allen, R. D. III, Collins, J., and Speck, S. H. (2007). ORF73-null murine gammaherpesvirus 68 reveals roles for mLANA and p53 in virus replication. J. Virol. 81, 11957-11971. doi: 10.1128/JVI.00111-07
31. Fowler, P., Marques, S., Simas, J. P., and Efstathiou, S. (2003). ORF73 of murine herpesvirus-68 is critical for the establishment and maintenance of latency. J. Gen. Virol. 84, 3405-3416. doi: 10.1099/vir.0.19594-0
32. Fujimuro, M., Liu, J., Zhu, J., Yokosawa, H., and Hayward, S. D. (2005). Regulation of the interaction between glycogen synthase kinase 3 and the Kaposi's sarcoma-associated herpesvirus latency-associated nuclear antigen. J. Virol. 79, 10429-10441. doi: 10.1128/JVI.79.16.10429-10441.2005
33. Garber, A. C., Hu, J., and Renne, R. (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, 27401-27411. doi: 10.1074/jbc.M203489200
34. Garber, A. C., Shu, M. A., Hu, J., and Renne, R. (2001). DNA binding and modulation of gene expression by the latency-associated nuclear antigen of Kaposi's sarcoma-associated herpesvirus. J. Virol. 75, 7882-7892. doi: 10.1128/JVI.75.17.7882-7892.2001
35. Griffiths, R., and Whitehouse, A. (2007). Herpesvirus saimiri episomal persistence is maintained via interaction between open reading frame 73 and the cellular chromosome-associated protein MeCP2. J. Virol. 81, 4021-4032. doi: 10.1128/JVI.02171-06
36. Grogan, E. A., Summers, W. P., Dowling, S., Shedd, D., Gradoville, L., and Miller, G. (1983). Two Epstein-Barr viral nuclear neoantigens distinguished by gene transfer, serology, and chromosome binding. Proc. Natl. Acad. Sci. U.S.A. 80, 7650-7653. doi: 10.1073/pnas.80.24.7650
37. Grundhoff, A., and Ganem, D. (2003). The latency-associated nuclear antigen of Kaposi's sarcoma-associated herpesvirus permits replication of terminal repeat-containing plasmids. J. Virol. 77, 2779-2783. doi: 10.1128/JVI.77.7.4470.2003
38. Grundhoff, A., and Ganem, D. (2004). Inefficient establishment of KSHV latency suggests an additional role for continued lytic replication in Kaposi sarcoma pathogenesis. J. Clin. Invest. 113, 124-136. doi: 10.1172/JCI200417803
39. Habison, A. C., Beauchemin, C., Simas, J. P., Usherwood, E. J., and Kaye, K. M. (2012). Murine gammaherpesvirus 68 LANA acts on terminal repeat DNA to mediate episome persistence. J. Virol. 86, 11863-11876. doi: 10.1128/JVI.01656-12
40. Han, S. J., Hu, J., Pierce, B., Weng, Z., and Renne, R. (2010). Mutational analysis of the latency-associated nuclear antigen DNA-binding domain of Kaposi's sarcoma-associated herpesvirus reveals structural conservation among gammaherpesvirus origin-binding proteins. J. Gen. Virol. 91, 2203-2215. doi: 10.1099/vir.0.020958-0
41. Harris, A., Young, B. D., and Griffin, B. E. (1985). Random association of Epstein-Barr virus genomes with host cell metaphase chromosomes in Bukitt's lymphoma-derived cell lines. J. Virol. 56, 328-332.
42. Hegde, R. S., Grossman, S. R., Laimins, L. A., and Sigler, P. B. (1992). Crystal structure at 1.7 A of the bovine papillomavirus-1 E2 DNA-binding domain bound to its DNA target [see comments]. Nature 359, 505-512. doi: 10.1038/359505a0
43. Hellert, J., Weidner-Glunde, M., Krausze, J., Lunsdorf, H., Ritter, C., Schulz, T. F., et al. (2015). The 3D structure of Kaposi sarcoma herpesvirus LANA C-terminal domain bound to DNA. Proc. Natl. Acad. Sci. U.S.A. 112, 6694-6699. doi: 10.1073/pnas.1421804112
44. Hellert, J., Weidner-Glunde, M., Krausze, J., Richter, U., Adler, H., Fedorov, R., et al. (2013). A structural basis for BRD2/4-mediated host chromatin interaction and oligomer assembly of Kaposi sarcoma-associated herpesvirus and murine gammaherpesvirus LANA proteins. PLoS Pathog. 9:e1003640. doi: 10.1371/journal.ppat.1003640
45. Hu, J., Liu, E., and Renne, R. (2009). Involvement of SSRP1 in latent replication of Kaposi's sarcoma-associated herpesvirus. J. Virol. 83, 11051-11063. doi: 10.1128/JVI.00907-09
46. Hu, J., and Renne, R. (2005). Characterization of the minimal replicator of Kaposi's sarcoma-associated herpesvirus latent origin. J. Virol. 79, 2637-2642. doi: 10.1128/JVI.79.4.2637-2642.2005
47. Hu, J., Yang, Y., Turner, P. C., Jain, V., Mcintyre, L. M., and Renne, R. (2014). LANA binds to multiple active viral and cellular promoters and associates with the H3K4Methyltransferase hSET1 complex. PLoS Pathog. 10:e1004240. doi: 10.1371/journal.ppat.1004240
48. Jager, W., Santag, S., Weidner-Glunde, M., Gellermann, E., Kati, S., Pietrek, M., et al. (2012). The ubiquitin-specific protease USP7 modulates the replication of Kaposi's sarcoma-associated herpesvirus latent episomal DNA. J. Virol. 86, 6745-6757. doi: 10.1128/JVI.06840-11
49. Jha, H. C., Upadhyay, S. K., Prasad, A. J. M., Lu, J., Cai, Q., Saha, A., et al. (2013). H2AX phosphorylation is important for LANA-mediated Kaposi's sarcoma-associated herpesvirus episome persistence. J. Virol. 87, 5255-5269. doi: 10.1128/JVI.03575-12
50. Kanda, T., Kamiya, M., Maruo, S., Iwakiri, D., and Takada, K. (2007). Symmetrical localization of extrachromosomally replicating viral genomes on sister chromatids. J. Cell Sci. 120, 1529-1539. doi: 10.1242/jcs.03434
51. Kedes, D. H., Lagunoff, M., Renne, R., and Ganem, D. (1997). Identification of the gene encoding the major latency-associated nuclear antigen of the Kaposi's sarcoma-associated herpesvirus. J. Clin. Invest. 100, 2606-2610. doi: 10.1172/JCI119804
52. Kellam, P., Boshoff, C., Whitby, D., Matthews, S., Weiss, R. A., and Talbot, S. J. (1997). Identification of a major latent nuclear antigen, LNA-1, in the human herpesvirus 8 genome. J. Hum. Virol. 1, 19-29.
53. Kelley-Clarke, B., Ballestas, M. E., Komatsu, T., and Kaye, K. M. (2007a). Kaposi's sarcoma herpesvirus C-terminal LANA concentrates at pericentromeric and peri-telomeric regions of a subset of mitotic chromosomes. Virology 357, 149-157. doi: 10.1016/j.virol.2006.07.052
54. Kelley-Clarke, B., Ballestas, M. E., Srinivasan, V., Barbera, A. J., Komatsu, T., Harris, T. A., et al. (2007b). Determination of Kaposi's sarcoma-associated herpesvirus C-terminal latency-associated nuclear antigen residues mediating chromosome association and DNA binding. J. Virol. 81, 4348-4356. doi: 10.1128/JVI.01289-06
55. Kelley-Clarke, B., De Leon-Vazquez, E., Slain, K., Barbera, A. J., and Kaye, K. M. (2009). Role of Kaposi's sarcoma-associated herpesvirus C-terminal LANA chromosome binding in episome persistence. J. Virol. 83, 4326-4337. doi: 10.1128/JVI.02395-08
56. Komatsu, T., Ballestas, M. E., Barbera, A. J., Kelley-Clarke, B., and Kaye, K. M. (2004). KSHV LANA1 binds DNA as an oligomer and residues N-terminal to the oligomerization domain are essential for DNA binding, replication, and episome persistence. Virology 319, 225-236. doi: 10.1016/j.virol.2003.11.002
57. Krithivas, A., Fujimuro, M., Weidner, M., Young, D. B., and Hayward, S. D. (2002). Protein interactions targeting the latency-associated nuclear antigen of Kaposi's sarcoma-associated herpesvirus to cell chromosomes. J. Virol. 76, 11596-11604. doi: 10.1128/JVI.76.22.11596-11604.2002
58. Leight, E. R., and Sugden, B. (2001). Establishment of an oriP replicon is dependent upon an infrequent, epigenetic event. Mol. Cell. Biol. 21, 4149-4161. doi: 10.1128/MCB.21.13.4149-4161.2001
59. Li, Q., Zhou, F., Ye, F., and Gao, S. J. (2008). Genetic disruption of KSHV major latent nuclear antigen LANA enhances viral lytic transcriptional program. Virology 379, 234-244. doi: 10.1016/j.virol.2008.06.043
60. Li, S., Tan, M., Juillard, F., Ponnusamy, R., Correia, B., Simas, J. P., et al. (2015). The Kaposi's sarcoma herpesvirus latency-associated nuclear antigen DNA binding domain dorsal positive electrostatic patch facilitates DNA replication and episome persistence. J. Biol. Chem. 290, 28084-28096. doi: 10.1074/jbc.M115.674622
61. Lim, C., Choi, C., and Choe, J. (2004). Mitotic chromosome-binding activity of latency-associated nuclear antigen 1 is required for DNA replication from terminal repeat sequence of Kaposi's sarcoma-associated herpesvirus. J. Virol. 78, 7248-7256. doi: 10.1128/JVI.78.13.7248-7256.2004
62. Lim, C., Lee, D., Seo, T., Choi, C., and Choe, J. (2003). Latency-associated nuclear antigen of Kaposi's sarcoma-associated herpesvirus functionally interacts with heterochromatin protein 1. J. Biol. Chem. 278, 7397-7405. doi: 10.1074/jbc.M211912200
63. Lim, C., Sohn, H., Lee, D., Gwack, Y., and Choe, J. (2002). Functional dissection of latency-associated nuclear antigen 1 of Kaposi's sarcoma-associated herpesvirus involved in latent DNA replication and transcription of terminal repeats of the viral genome. J. Virol. 76, 10320-10331. doi: 10.1128/JVI.76.20.10320-10331.2002
64. Liu, J., Martin, H., Shamay, M., Woodard, C., Tang, Q. Q., and Hayward, S. D. (2007). Kaposi's sarcoma-associated herpesvirus LANA protein downregulates nuclear glycogen synthase kinase 3 activity and consequently blocks differentiation. J. Virol. 81, 4722-4731. doi: 10.1128/JVI.02548-06
65. Lu, F., Day, L., Gao, S. J., and Lieberman, P. M. (2006). Acetylation of the latency-associated nuclear antigen regulates repression of Kaposi's sarcoma-associated herpesvirus lytic transcription. J. Virol. 80, 5273-5282. doi: 10.1128/JVI.02541-05
66. Lu, F., Tsai, K., Chen, H. S., Wikramasinghe, P., Davuluri, R. V., Showe, L., et al. (2012). Identification of host-chromosome binding sites and candidate gene targets for Kaposi's sarcoma-associated herpesvirus LANA. J. Virol. 86, 5752-5762. doi: 10.1128/JVI.07216-11
67. Matsumura, S., Persson, L. M., Wong, L., and Wilson, A. C. (2010). The latency-associated nuclear antigen interacts with MeCP2 and nucleosomes through separate domains. J. Virol. 84, 2318-2330. doi: 10.1128/JVI.01097-09
68. Mercier, A., Arias, C., Madrid, A. S., Holdorf, M. M., and Ganem, D. (2014). Site-specific association with host and viral chromatin by Kaposi's sarcoma-associated herpesvirus LANA and its reversal during lytic reactivation. J. Virol. 88, 6762-6777. doi: 10.1128/JVI.00268-14
69. Moorman, N. J., Willer, D. O., and Speck, S. H. (2003). The gammaherpesvirus 68 latency-associated nuclear antigen homolog is critical for the establishment of splenic latency. J. Virol. 77, 10295-10303. doi: 10.1128/JVI.77.19.10295-10303.2003
70. Nanbo, A., Sugden, A., and Sugden, B. (2007). The coupling of synthesis and partitioning of EBV's plasmid replicon is revealed in live cells. EMBO J. 26, 4252-4262. doi: 10.1038/sj.emboj.7601853
71. Norby, K., Chiu, Y. F., and Sugden, B. (2012). Monitoring plasmid replication in live mammalian cells over multiple generations by fluorescence microscopy. J. Vis. Exp. 70:e4305. doi: 10.3791/4305
72. Ohsaki, E., Ueda, K., Sakakibara, S., Do, E., Yada, K., and Yamanishi, K. (2004). Poly(ADP-ribose) polymerase 1 binds to Kaposi's sarcoma-associated herpesvirus (KSHV) terminal repeat sequence and modulates KSHV replication in latency. J. Virol. 78, 9936-9946. doi: 10.1128/JVI.78.18.9936-9946.2004
73. Oliveira, J. G., Colf, L. A., and Mcbride, A. A. (2006). Variations in the association of papillomavirus E2 proteins with mitotic chromosomes. Proc. Natl. Acad. Sci. U.S.A. 103, 1047-1052. doi: 10.1073/pnas.0507624103
74. Ottinger, M., Christalla, T., Nathan, K., Brinkmann, M. M., Viejo-Borbolla, A., and Schulz, T. F. (2006). Kaposi's sarcoma-associated herpesvirus LANA-1 interacts with the short variant of BRD4 and releases cells from a BRD4-and BRD2/RING3-induced G1 cell cycle arrest. J. Virol. 80, 10772-10786. doi: 10.1128/JVI.00804-06
75. Paden, C. R., Forrest, J. C., Moorman, N. J., and Speck, S. H. (2010). Murine gammaherpesvirus 68 LANA is essential for virus reactivation from splenocytes but not long-term carriage of viral genome. J. Virol. 84, 7214-7224. doi: 10.1128/JVI.00133-10
76. Paden, C. R., Forrest, J. C., Tibbetts, S. A., and Speck, S. H. (2012). Unbiased mutagenesis of MHV68 LANA reveals a DNA-binding domain required for LANA function in vitro and in vivo. PLoS Pathog. 8:e1002906. doi: 10.1371/journal.ppat.1002906
77. Piolot, T., Tramier, M., Coppey, M., Nicolas, J. C., and Marechal, V. (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, 3948-3959. doi: 10.1128/JVI.75.8.3948-3959.2001
78. Platt, G. M., Simpson, G. R., Mittnacht, S., and Schulz, T. F. (1999). Latent nuclear antigen of Kaposi's sarcoma-associated herpesvirus interacts with RING3, a homolog of the Drosophila female sterile homeotic (fsh) gene. J. Virol. 73, 9789-9795.
79. Ponnusamy, R., Petoukhov, M. V., Correia, B., Custodio, T. F., Juillard, F., Tan, M., et al. (2015). KSHV but not MHV-68 LANA induces a strong bend upon binding to terminal repeat viral DNA. Nucleic Acids Res. 43, 10039-10054. doi: 10.1093/nar/gkv987
80. Purushothaman, P., Mcdowell, M. E., Mcguinness, J., Salas, R., Rumjahn, S. M., and Verma, S. C. (2012). Kaposi's sarcoma-associated herpesvirus-encoded LANA recruits topoisomerase iibeta for latent DNA replication of the terminal repeats. J. Virol. 86, 9983-9994. doi: 10.1128/JVI.00839-12
81. Rainbow, L., Platt, G. M., Simpson, G. R., Sarid, R., Stoiber, S.-J. G., Herrington, C. S., et al. (1997). The 222-to 234-kilodalton latent nuclear protein (LNA) of Kaposi's sarcoma-associated herpesvirus is encoded by orf73 and is a component of the latency-associated nuclear antigen. J. Virol. 71, 5915-5921.
82. Reedman, B. M., and Klein, G. (1973). Cellular localization of an Epstein-Barr virus (EBV)-associated complement-fixing antigen in producer and non-producer lymphoblastoid cell lines. Int. J. Cancer 11, 499-520. doi: 10.1002/ijc.2910110302
83. Reinberg, D., and Sims, R. J. III. (2006). de FACTo nucleosome dynamics. J. Biol. Chem. 281, 23297-23301. doi: 10.1074/jbc.R600007200
84. Rivas, C., Thlick, A. E., Parravicini, C., Moore, P. S., and Chang, Y. (2001). Kaposi's sarcoma-associated herpesvirus LANA2 is a B-cell-specific latent viral protein that inhibits p53. J. Virol. 75, 429-438. doi: 10.1128/JVI.75.1.429-438.2001
85. Russo, J. J., Bohenzky, R. A., Chien, M.-C., Chen, J., Yan, M., Maddalena, D., et al. (1996). Nucleotide sequence of the Kaposi sarcoma-associated herpesvirus (HHV8). Proc. Natl. Acad. Sci. U.S.A. 93, 14862-14867. doi: 10.1073/pnas.93.25.14862
86. Sadler, R., Wu, L., Forghani, B., Renne, R., Zhong, W., Herndier, B., et al. (1999). A complex translational program generates multiple novel proteins from the latently expressed kaposin (K12) locus of Kaposi's sarcoma-associated herpesvirus. J. Virol. 73, 5722-5730.
87. Sakakibara, S., Ueda, K., Nishimura, K., Do, E., Ohsaki, E., Okuno, T., et al. (2004). Accumulation of heterochromatin components on the terminal repeat sequence of Kaposi's sarcoma-associated herpesvirus mediated by the latency-associated nuclear antigen. J. Virol. 78, 7299-7310. doi: 10.1128/JVI.78.14.7299-7310.2004
88. Samols, M. A., Hu, J., Skalsky, R. L., and Renne, R. (2005). Cloning and identification of a microRNA cluster within the latency-associated region of Kaposi's sarcoma-associated herpesvirus. J. Virol. 79, 9301-9305. doi: 10.1128/JVI.79.14.9301-9305.2005
89. Schwam, D. R., Luciano, R. L., Mahajan, S. S., Wong, L., and Wilson, A. C. (2000). Carboxy terminus of human herpesvirus 8 latency-associated nuclear antigen mediates dimerization, transcriptional repression, and targeting to nuclear bodies [In Process Citation]. J. Virol. 74, 8532-8540. doi: 10.1128/JVI.74.18.8532-8540.2000
90. Shamay, M., Liu, J., Li, R., Liao, G., Shen, L., Greenway, M., et al. (2012). A protein array screen for KSHV LANA interactors links LANA to TIP60, PP2A activity and telomere shortening. J. Virol. 86, 5179-5191. doi: 10.1128/JVI.00169-12
91. Shinohara, H., Fukushi, M., Higuchi, M., Oie, M., Hoshi, O., Ushiki, T., et al. (2002). Chromosome binding site of latency-associated nuclear antigen of Kaposi's sarcoma-associated herpesvirus is essential for persistent episome maintenance and is functionally replaced by histone H1. J. Virol. 76, 12917-12924. doi: 10.1128/JVI.76.24.12917-12924.2002
92. Si, H., Verma, S. C., Lampson, M. A., Cai, Q., and Robertson, E. S. (2008). Kaposi's sarcoma-associated herpesvirus-encoded LANA can interact with the nuclear mitotic apparatus protein to regulate genome maintenance and segregation. J. Virol. 82, 6734-6746. doi: 10.1128/JVI.00342-08
93. Skalsky, R. L., Hu, J., and Renne, R. (2007). Analysis of viral cis elements conferring Kaposi's sarcoma-associated herpesvirus episome partitioning and maintenance. J. Virol. 81, 9825-9837. doi: 10.1128/JVI.00842-07
94. Srinivasan, V., Komatsu, T., Ballestas, M. E., and Kaye, K. M. (2004). Definition of sequence requirements for latency-associated nuclear antigen 1 binding to Kaposi's sarcoma-associated herpesvirus DNA. J. Virol. 78, 14033-14038. doi: 10.1128/JVI.78.24.14033-14038.2004
95. Stedman, W., Deng, Z., Lu, F., and Lieberman, P. M. (2004). ORC, MCM, and histone hyperacetylation at the Kaposi's sarcoma-associated herpesvirus latent replication origin. J. Virol. 78, 12566-12575. doi: 10.1128/JVI.78.22.12566-12575.2004
96. Sun, Q., Tsurimoto, T., Juillard, F., Li, L., Li, S., De Leon Vazquez, E., et al. (2014). Kaposi's sarcoma-associated herpesvirus LANA recruits the DNA polymerase clamp loader to mediate efficient replication and virus persistence. Proc. Natl. Acad. Sci. U.S.A. 111, 11816-11821. doi: 10.1073/pnas.1404219111
97. Sun, Z., Jha, H. C., and Robertson, E. S. (2015). Bub1 in complex with LANA recruits PCNA to regulate Kaposi's sarcoma-associated herpesvirus latent replication and DNA translesion synthesis. J. Virol. 89, 10206-10218. doi: 10.1128/JVI.01524-15
98. Sun, Z., Xiao, B., Jha, H. C., Lu, J., Banerjee, S., and Robertson, E. S. (2014). Kaposi's sarcoma-associated herpesvirus-encoded LANA can induce chromosomal instability through targeted degradation of the mitotic checkpoint kinase Bub1. J. Virol. 88, 7367-7378. doi: 10.1128/JVI.00554-14
99. Szekely, L., Kiss, C., Mattsson, K., Kashuba, E., Pokrovskaja, K., Juhasz, A., et al. (1999). Human herpesvirus-8-encoded LNA-1 accumulates in heterochromatin-associated nuclear bodies. J. Gen. Virol. 80, 2889-2900. doi: 10.1099/0022-1317-80-11-2889
100. Tan, B. C., Chien, C. T., Hirose, S., and Lee, S. C. (2006). Functional cooperation between FACT and MCM helicase facilitates initiation of chromatin DNA replication. EMBO J. 25, 3975-3985. doi: 10.1038/sj.emboj.7601271
101. Tetsuka, T., Higuchi, M., Fukushi, M., Watanabe, A., Takizawa, S., Oie, M., et al. (2004). Visualization of a functional KSHV episome-maintenance protein LANA in living cells. Virus Genes 29, 175-182. doi: 10.1023/B:VIRU.0000036377.48454.d8
102. Ueda, K., Sakakibara, S., Ohsaki, E., and Yada, K. (2006). Lack of a mechanism for faithful partition and maintenance of the KSHV genome. Virus Res. 122, 85-94. doi: 10.1016/j.virusres.2006.07.002
103. Verma, S. C., Cai, Q., Kreider, E., Lu, J., and Robertson, E. S. (2013). Comprehensive analysis of LANA interacting proteins essential for viral genome tethering and persistence. PLoS ONE 8:e74662. doi: 10.1371/journal.pone.0074662
104. Verma, S. C., Choudhuri, T., Kaul, R., and Robertson, E. S. (2006). Latency-associated nuclear antigen (LANA) of Kaposi's sarcoma-associated herpesvirus interacts with origin recognition complexes at the LANA binding sequence within the terminal repeats. J. Virol. 80, 2243-2256. doi: 10.1128/JVI.80.5.2243-2256.2006
105. Verma, S. C., Choudhuri, T., and Robertson, E. S. (2007). The minimal replicator element of the Kaposi's sarcoma-associated herpesvirus terminal repeat supports replication in a semiconservative and cell-cycle-dependent manner. J. Virol. 81, 3402-3413. doi: 10.1128/JVI.01607-06
106. Viejo-Borbolla, A., Kati, E., Sheldon, J. A., Nathan, K., Mattsson, K., Szekely, L., et al. (2003). A Domain in the C-terminal region of latency-associated nuclear antigen 1 of Kaposi's sarcoma-associated Herpesvirus affects transcriptional activation and binding to nuclear heterochromatin. J. Virol. 77, 7093-7100. doi: 10.1128/JVI.77.12.7093-7100.2003
107. Viejo-Borbolla, A., Ottinger, M., Bruning, E., Burger, A., Konig, R., Kati, E., et al. (2005). Brd2/RING3 interacts with a chromatin-binding domain in the Kaposi's Sarcoma-associated herpesvirus latency-associated nuclear antigen 1 (LANA-1) that is required for multiple functions of LANA-1. J. Virol. 79, 13618-13629. doi: 10.1128/JVI.79.21.13618-13629.2005
108. Wong, L. Y., Matchett, G. A., and Wilson, A. C. (2004). Transcriptional activation by the Kaposi's sarcoma-associated herpesvirus latency-associated nuclear antigen is facilitated by an N-terminal chromatin-binding motif. J. Virol. 78, 10074-10085. doi: 10.1128/JVI.78.18.10074-10085.2004
109. Wong, L. Y., and Wilson, A. C. (2005). Kaposi's sarcoma-associated herpesvirus latency-associated nuclear antigen induces a strong bend on binding to terminal repeat DNA. J. Virol. 79, 13829-13836. doi: 10.1128/JVI.79.21.13829-13836.2005
110. Woodard, C., Shamay, M., Liao, G., Zhu, J., Ng, A. N., Li, R., et al. (2012). Phosphorylation of the chromatin binding domain of KSHV LANA. PLoS Pathog. 8:e1002972. doi: 10.1371/journal.ppat.1002972
111. Xiao, B., Verma, S. C., Cai, Q., Kaul, R., Lu, J., Saha, A., et al. (2010). Bub1 and CENP-F can contribute to Kaposi's sarcoma-associated herpesvirus genome persistence by targeting LANA to kinetochores. J. Virol. 84, 9718-9732. doi: 10.1128/JVI.00713-10
112. Yates, J., Warren, N., Reisman, D., and Sugden, B. (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. U.S.A. 81, 3806-3810. doi: 10.1073/pnas.81.12.3806
113. You, J., Croyle, J. L., Nishimura, A., Ozato, K., and Howley, P. M. (2004). Interaction of the bovine papillomavirus E2 protein with Brd4 tethers the viral DNA to host mitotic chromosomes. Cell 117, 349-360. doi: 10.1016/S0092-8674(04)00402-7
114. You, J., Srinivasan, V., Denis, G. V., Harrington, W. J. Jr., Ballestas, M. E., Kaye, K. M., et al. (2006). Kaposi's sarcoma-associated herpesvirus latency-associated nuclear antigen interacts with bromodomain protein Brd4 on host mitotic chromosomes. J. Virol. 80, 8909-8919. doi: 10.1128/JVI.00502-06
115. Zhang, Y. J., Wang, K. Y., Stein, D. A., Patel, D., Watkins, R., Moulton, H. M., et al. (2007). Inhibition of replication and transcription activator and latency-associated nuclear antigen of Kaposi's sarcoma-associated herpesvirus by morpholino oligomers. Antiviral Res. 73, 12-23. doi: 10.1016/j.antiviral.2006.05.017