The latency-associated nuclear antigen, a multifunctional protein central to Kaposi's sarcoma-associated herpesvirus latency

Future Microbiology

Volumn 6, Issue 12, 2011, Pages 1399-1413

  Ballestas, Mary E ^a   Kaye, Kenneth M ^b  

^a University of Alabama at Birmingham and Children's Hospital   (United States)

^b BRIGHAM AND WOMEN S HOSPITAL   (United States)

Author keywords

AIDS; HIV; Human herpesvirus 8; Kaposi's sarcoma; Lymphoma; Viral latency

Indexed keywords

ACTIVATING TRANSCRIPTION FACTOR 4; DNA METHYLTRANSFERASE 1; DNA METHYLTRANSFERASE 3A; DNA METHYLTRANSFERASE 3B; ELONGIN C; GLYCOGEN SYNTHASE KINASE 3BETA; HISTONE H1; HISTONE H2A; HISTONE H2B; HYPOXIA INDUCIBLE FACTOR 1ALPHA; LATENCY ASSOCIATED NUCLEAR ANTIGEN; NUCLEOPHOSMIN; ORIGIN RECOGNITION COMPLEX; PROTEIN P53; RETINOBLASTOMA PROTEIN; TRANSACTIVATOR PROTEIN; VON HIPPEL LINDAU PROTEIN;

ACQUIRED IMMUNE DEFICIENCY SYNDROME; ANGIOFOLLICULAR LYMPH NODE HYPERPLASIA; APOPTOSIS; ARTICLE; BINDING AFFINITY; CELL CYCLE REGULATION; CELL DIVISION; CELL GROWTH; CELL SURVIVAL; CHROMATIN ASSEMBLY AND DISASSEMBLY; CHROMOSOME; DNA BINDING; DNA METHYLATION; DNA REPAIR; DNA REPLICATION; DNA SEQUENCE; EPISOME; GENETIC TRANSCRIPTION; HISTONE MODIFICATION; HUMAN HERPESVIRUS 8; MITOSIS; NONHUMAN; NUCLEOTIDE SEQUENCE; PRIMARY EFFUSION LYMPHOMA; PRIORITY JOURNAL; VIRUS GENE; VIRUS LATENCY; VIRUS NUCLEOCAPSID;

ANTIGENS, VIRAL; CELL DIVISION; CHROMOSOME SEGREGATION; DNA REPLICATION; DNA, VIRAL; HERPESVIRUS 8, HUMAN; HOST-PATHOGEN INTERACTIONS; HUMANS; NUCLEAR PROTEINS; PLASMIDS; VIRULENCE FACTORS; VIRUS LATENCY; VIRUS REPLICATION;

EID: 82455175430     PISSN: 17460913     EISSN: 17460921     Source Type: Journal    
DOI: 10.2217/fmb.11.137     Document Type: Article

References (182)

1. Chang Y, Cesarman E, Pessin MS et al. Identification of herpesvirus-like DNA sequences in AIDS-associated Kaposis sarcoma. Science 266(5192), 1865-1869 (1994).
2. Russo JJ, Bohenzky RA, Chien MC et al. Nucleotide sequence of the Kaposi sarcoma-associated herpesvirus (HHV8). Proc. Natl Acad. Sci. USA 93(25), 14862-14867 (1996).
3. Carbone A, Cesarman E, Spina M, Gloghini A, Schulz TF. HIV-associated lymphomas and gamma-herpesviruses. Blood 113(6), 1213-1224 (2009).
4. Jenner RG, Boshoff C. The molecular pathology of Kaposis sarcoma-associated herpesvirus. Biochim. Biophys. Acta 1602(1), 1-22 (2002).
5. Achenbach CJ, Cole SR, Kitahata MM et al. Mortality after cancer diagnosis in HIV-infected individuals treated with antiretroviral therapy. AIDS 25(5), 691-700 (2011).
6. Bihl F, Mosam A, Henry LN et al. Kaposis sarcoma-associated herpesvirus-specific immune reconstitution and antiviral effect of combined HAART/chemotherapy in HIV clade C-infected individuals with Kaposis sarcoma. AIDS 21(10), 1245-1252 (2007).
7. Bourboulia D, Aldam D, Lagos D et al. Short-and long-term effects of highly active antiretroviral therapy on Kaposi sarcoma-associated herpesvirus immune responses and viraemia. AIDS 18(3), 485-493 (2004).
8. Gao SJ, Kingsley L, Hoover DR et al. Seroconversion to antibodies against Kaposis sarcoma-associated herpesvirus-related latent nuclear antigens before the development of Kaposis sarcoma. N. Engl. J. Med. 335(4), 233-241 (1996).
9. Qunibi WY, Barri Y, Alfurayh O et al. Kaposis sarcoma in renal transplant recipients: a report on 26 cases from a single institution. Transplant Proc. 25(1 Pt 2), 1402-1405 (1993).
10. Kasolo FC, Mpabalwani E, Gompels UA. Infection with AIDS-related herpesviruses in human immunodeficiency virus-negative infants and endemic childhood Kaposis sarcoma in Africa. J. Gen. Virol. 78 (Pt 4), 847-855 (1997).
11. Sarmati L. HHV-8 infection in African children. Herpes 11(2), 50-53 (2004).
12. Uldrick TS, Whitby D. Update on KSHV epidemiology, Kaposi Sarcoma pathogenesis, and treatment of Kaposi Sarcoma. Cancer Lett. 305(2), 150-162 (2011).
13. Gao SJ, Kingsley L, LI M et al. KSHV antibodies among Americans, Italians and Ugandans with and without Kaposis sarcoma. Nat. Med. 2(8), 925-928 (1996).
14. Boshoff C, Whitby D, Hatziioannou T et al. Kaposi's-sarcoma-associated herpesvirus in HIV-negative Kaposis sarcoma. Lancet 345(8956), 1043-1044 (1995).
15. Inoue N, Spira T, Lam L, Corchero JL, Luo W. Comparison of serologic responses between Kaposis sarcoma-positive and -negative men who were seropositive for both human herpesvirus 8 and human immunodeficiency virus. J. Med. Virol. 74(2), 202-206 (2004).
16. Martin JN, Ganem DE, Osmond DH, Page-Shafer KA, Macrae D, Kedes DH. Sexual transmission and the natural history of human herpesvirus 8 infection. N. Engl. J. Med. 338(14), 948-954 (1998).
17. Simpson GR, Schulz TF, Whitby D et al. Prevalence of Kaposis sarcoma associated herpesvirus infection measured by antibodies to recombinant capsid protein and latent immunofluorescence antigen. Lancet 348(9035), 1133-1138 (1996).
18. Spira TJ, Lam L, Dollard SC et al. Comparison of serologic assays and PCR for diagnosis of human herpesvirus 8 infection. J. Clin. Microbiol. 38(6), 2174-2180 (2000).
19. Kedes DH, Lagunoff M, Renne R, Ganem D. Identification of the gene encoding the major latency-associated nuclear antigen of the Kaposis sarcoma-associated herpesvirus. J. Clin. Invest. 100(10), 2606-2610 (1997).
20. Rainbow L, Platt GM, Simpson GR et al. The 222-to 234-kilodalton latent nuclear protein (LNA) of Kaposis sarcoma-associated herpesvirus (human herpesvirus 8) is encoded by orf73 and is a component of the latency-associated nuclear antigen. J. Virol. 71(8), 5915-5921 (1997).
21. Gao SJ, Zhang YJ, Deng JH, Rabkin CS, Flore O, Jenson HB. Molecular polymorphism of Kaposis sarcoma-associated herpesvirus (Human herpesvirus 8) latent nuclear antigen: evidence for a large repertoire of viral genotypes and dual infection with different viral genotypes. J. Infect. Dis. 180(5), 1466-1476 (1999).
22. Efstathiou S, HO YM, Minson AC. Cloning and molecular characterization of the murine herpesvirus 68 genome. J. Gen. Virol. 71(Pt 6), 1355-1364 (1990).
23. Schafer A, Lengenfelder D, Grillhosl C, Wieser C, Fleckenstein B, Ensser A. The latency-associated nuclear antigen homolog of herpesvirus saimiri inhibits lytic virus replication. J. Virol. 77(10), 5911-5925 (2003).
24. Rose TM, Strand KB, Schultz ER et al. Identification of two homologs of the Kaposis sarcoma-associated herpesvirus (human herpesvirus 8) in retroperitoneal fibromatosis of different macaque species. J. Virol. 71(5), 4138-4144 (1997).
25. Schultz ER, Rankin GW Jr, Blanc MP, Raden BW, Tsai CC, Rose TM. Characterization of two divergent lineages of macaque rhadinoviruses related to Kaposis sarcoma-associated herpesvirus. J. Virol. 74(10), 4919-4928 (2000).
26. Burnside KL, Ryan JT, Bielefeldt-Ohmann H et al. 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(1), 103-115 (2006).
27. Barbera AJ, Chodaparambil JV, Kelley-Clarke β et al. The nucleosomal surface as a docking station for Kaposis sarcoma herpesvirus LANA. Science 311(5762), 856-861 (2006).
28. Gottwein E, Mukherjee N, Sachse C et al. A viral microRNA functions as an orthologue of cellular miR-155. Nature 450(7172), 1096-1099 (2007).
29. Samols MA, HU J, Skalsky RL, Renne R. Cloning and identification of a microRNA cluster within the latency-associated region of Kaposis sarcoma-associated herpesvirus. J. Virol. 79(14), 9301-9305 (2005).
30. Ballestas ME, Kaye KM. Kaposis 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(7), 3250-3258 (2001).
31. Cotter MA, 2nd, Robertson ES. The latency-associated nuclear antigen tethers the Kaposis sarcoma-associated herpesvirus genome to host chromosomes in body cavity-based lymphoma cells. Virology 264(2), 254-264 (1999).
32. Grundhoff A, Ganem D. The latency-associated nuclear antigen of Kaposis sarcoma-associated herpesvirus permits replication of terminal repeat-containing plasmids. J. Virol. 77(4), 2779-2783 (2003).
33. Alberter B, Ensser A. Histone modification pattern of the T-cellular Herpesvirus saimiri genome in latency. J. Virol. 81(5), 2524-2530 (2007).
34. Lu F, Stedman W, Yousef M, Renne R, Lieberman PM. Epigenetic regulation of Kaposis sarcoma-associated herpesvirus latency by virus-encoded microRNAs that target Rta and the cellular Rbl2-DNMT pathway. J. Virol. 84(6), 2697-2706 (2010).
35. Stedman W, Deng Z, Lu F, Lieberman PM. ORC, MCM, and histone hyperacetylation at the Kaposis sarcoma-associated herpesvirus latent replication origin. J. Virol. 78(22), 12566-12575 (2004).
36. Barbera AJ, Ballestas ME, Kaye KM. The Kaposis sarcoma-associated herpesvirus latency-associated nuclear antigen 1 N terminus is essential for chromosome association, DNA replication, and episome persistence. J. Virol. 78(1), 294-301 (2004).
37. Kelley-Clarke B, Ballestas ME, Komatsu T, Kaye KM. Kaposis sarcoma herpesvirus C-terminal LANA concentrates at pericentromeric and peri-telomeric regions of a subset of mitotic chromosomes. Virology 357(2), 149-157 (2007).
38. Piolot T, Tramier M, Coppey M, Nicolas JC, Marechal V. 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(8), 3948-3959 (2001).
39. Chodaparambil JV, Barbera AJ, Lu X, Kaye KM, Hansen JC, Luger K. A charged and contoured surface on the nucleosome regulates chromatin compaction. Nat. Struct. Mol Biol. 14(11), 1105-1107 (2007).
40. Roussel L, Erard M, Cayrol C, Girard JP. Molecular mimicry between IL-33 and KSHV for attachment to chromatin through the H2A-H2B acidic pocket. EMBO Rep. 9(10), 1006-1012 (2008).
41. Ballestas ME, Chatis PA, Kaye KM. Efficient persistence of extrachromosomal KSHV DNA mediated by latency-associated nuclear antigen. Science 284(5414), 641-644 (1999).
42. Abbate EA, Voitenleitner C, Botchan MR. Structure of the papillomavirus DNA-tethering complex E2:Brd4 and a peptide that ablates HPV chromosomal association. Mol. Cell 24(6), 877-889 (2006).
43. Yates J, Warren N, Reisman D, Sugden B. 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(12), 3806-3810 (1984).
44. Sugden B, Marsh K, Yates J. A vector that replicates as a plasmid and can be efficiently selected in B-lymphoblasts transformed by Epstein-Barr virus. Mol. Cell Biol. 5(2), 410-413 (1985).
45. Yates JL, Warren N, Sugden B. Stable replication of plasmids derived from Epstein-Barr virus in various mammalian cells. Nature 313(6005), 812-815 (1985).
46. Bastien N, Mcbride AA. Interaction of the papillomavirus E2 protein with mitotic chromosomes. Virology 270(1), 124-134 (2000).
47. Dao LD, Duffy A, Van Tine BA et al. Dynamic localization of the human papillomavirus type 11 origin binding protein E2 through mitosis while in association with the spindle apparatus. J. Virol. 80(10), 4792-4800 (2006).
48. Oliveira JG, Colf LA, Mcbride AA. Variations in the association of papillomavirus E2 proteins with mitotic chromosomes. Proc. Natl Acad. Sci. USA 103(4), 1047-1052 (2006).
49. You J, Croyle JL, Nishimura A, Ozato K, Howley PM. Interaction of the bovine papillomavirus E2 protein with Brd4 tethers the viral DNA to host mitotic chromosomes. Cell 117(3), 349-360 (2004).
50. Szekely L, Kiss C, Mattsson K et al. Human herpesvirus-8-encoded LNA-1 accumulates in heterochromatin-associated nuclear bodies. J. Gen. Virol. 80 (Pt 11), 2889-2900 (1999).
51. Kelley-Clarke B, DE Leon-Vazquez E, Slain K, Barbera AJ, Kaye KM. Role of Kaposis sarcoma-associated herpesvirus C-terminal LANA chromosome binding in episome persistence. J. Virol. 83(9), 4326-4337 (2009).
52. Xiao B, Verma SC, Cai Q et al. Bub1 and CENP-F can contribute to Kaposis sarcoma-associated herpesvirus genome persistence by targeting LANA to kinetochores. J. Virol. 84(19), 9718-9732 (2010).
53. Kanda T, Kamiya M, Maruo S, Iwakiri D, Takada K. Symmetrical localization of extrachromosomally replicating viral genomes on sister chromatids. J. Cell Sci. 120(Pt 9), 1529-1539 (2007).
54. Nanbo A, Sugden A, Sugden B. The coupling of synthesis and partitioning of EBV's plasmid replicon is revealed in live cells. EMBO J. 26(19), 4252-4262 (2007).
55. Hu J, Renne R. Characterization of the minimal replicator of Kaposis sarcoma-associated herpesvirus latent origin. J. Virol. 79(4), 2637-2642 (2005).
56. Komatsu T, Ballestas ME, Barbera AJ, Kelley-Clarke B, Kaye KM. 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(2), 225-236 (2004).
57. Komatsu T, Barbera AJ, Ballestas ME, Kaye KM. The Kaposi' s sarcoma-associated herpesvirus latency-associated nuclear antigen. Viral Immunol. 14(4), 311-317 (2001).
58. Srinivasan V, Komatsu T, Ballestas ME, Kaye KM. Definition of sequence requirements for latency-associated nuclear antigen 1 binding to Kaposis sarcoma-associated herpesvirus DNA. J. Virol. 78(24), 14033-14038 (2004).
59. Garber AC, HU J, Renne R. 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(30), 27401-27411 (2002).
60. Schwam DR, Luciano RL, Mahajan SS, Wong L, Wilson AC. Carboxy terminus of human herpesvirus 8 latency-associated nuclear antigen mediates dimerization, transcriptional repression, and targeting to nuclear bodies. J. Virol. 74(18), 8532-8540 (2000).
61. Bochkarev A, Barwell JA, Pfuetzner RA, Bochkareva E, Frappier L, Edwards AM. Crystal structure of the DNA-binding domain of the Epstein-Barr virus origin-binding protein, EBNA1, bound to DNA. Cell 84(5), 791-800 (1996).
62. Hegde RS, Androphy EJ. Crystal structure of the E2 DNA-binding domain from human papillomavirus type 16: implications for its DNA binding-site selection mechanism. J. Mol. Biol. 284(5), 1479-1489 (1998).
63. Krithivas A, Fujimuro M, Weidner M, Young DB, Hayward SD. Protein interactions targeting the latency-associated nuclear antigen of Kaposis sarcoma-associated herpesvirus to cell chromosomes. J. Virol. 76(22), 11596-11604 (2002).
64. Krithivas A, Young DB, Liao G, Greene D, Hayward SD. Human herpesvirus 8 LANA interacts with proteins of the mSin3 corepressor complex and negatively regulates Epstein-Barr virus gene expression in dually infected PEL cells. J. Virol. 74(20), 9637-9645 (2000).
65. Lim C, Lee D, Seo T, Choi C, Choe J. Latency-associated nuclear antigen of Kaposis sarcoma-associated herpesvirus functionally interacts with heterochromatin protein 1. J. Biol. Chem. 278(9), 7397-7405 (2003).
66. Matsumura S, Persson LM, Wong L, Wilson AC. The latency-associated nuclear antigen interacts with MeCP2 and nucleosomes through separate domains. J. Virol. 84(5), 2318-2330 (2010).
67. Verma SC, Choudhuri T, Kaul R, Robertson ES. Latency-associated nuclear antigen (LANA) of Kaposis sarcoma-associated herpesvirus interacts with origin recognition complexes at the LANA binding sequence within the terminal repeats. J. Virol. 80(5), 2243-2256 (2006).
68. Griffiths R, Whitehouse A. Herpesvirus saimiri episomal persistence is maintained via interaction between open reading frame 73 and the cellular chromosome-associated protein MeCP2. J. Virol. 81(8), 4021-4032 (2007).
69. Chahrour M, Jung SY, Shaw C et al. MeCP2, a key contributor to neurological disease, activates and represses transcription. Science 320(5880), 1224-1229 (2008).
70. Stuber G, Mattsson K, Flaberg E et al. HHV-8 encoded LANA-1 alters the higher organization of the cell nucleus. Mol. Cancer 6, 28 (2007).
71. Lewis PW, Elsaesser SJ, Noh KM, Stadler SC, Allis CD. Daxx is an H3.3-specific histone chaperone and cooperates with ATRX in replication- independent chromatin assembly at telomeres. Proc. Natl Acad. Sci. USA 107(32), 14075-14080 (2010).
72. Garber AC, Shu MA, HU J, Renne R. DNA binding and modulation of gene expression by the latency-associated nuclear antigen of Kaposis sarcoma-associated herpesvirus. J. Virol. 75(17), 7882-7892 (2001).
73. Skalsky RL, HU J, Renne R. Analysis of viral cis elements conferring Kaposis sarcoma-associated herpesvirus episome partitioning and maintenance. J. Virol. 81(18), 9825-9837 (2007).
74. Grundhoff A, Ganem D. Inefficient establishment of KSHV latency suggests an additional role for continued lytic replication in Kaposi sarcoma pathogenesis. J. Clin. Invest. 113(1), 124-136 (2004).
75. Fowler P, Marques S, Simas JP, Efstathiou S. ORF73 of murine herpesvirus-68 is critical for the establishment and maintenance of latency. J. Gen. Virol. 84(Pt 12), 3405-3416 (2003).
76. Li Q, Zhou F, YE F, Gao SJ. Genetic disruption of KSHV major latent nuclear antigen LANA enhances viral lytic transcriptional program. Virology 379(2), 234-244 (2008).
77. Wen KW, Dittmer DP, Damania B. Disruption of LANA in rhesus rhadinovirus generates a highly lytic recombinant virus. J. Virol. 83(19), 9786-9802 (2009).
78. Zhang YJ, Wang KY, Stein DA et al. Inhibition of replication and transcription activator and latency-associated nuclear antigen of Kaposis sarcoma-associated herpesvirus by morpholino oligomers. Antiviral Res. 73(1), 12-23 (2007).
79. Forrest JC, Paden CR, Allen RD 3rd, Collins J, Speck SH. ORF73-null murine gammaherpesvirus 68 reveals roles for mLANA and p53 in virus replication. J. Virol. 81(21), 11957-11971 (2007).
80. Jia Q, Freeman ML, Yager EJ et al. Induction of protective immunity against murine gammaherpesvirus 68 infection in the absence of viral latency. J. Virol. 84(5), 2453-2465 (2010).
81. Moorman NJ, Willer DO, Speck SH. The gammaherpesvirus 68 latency-associated nuclear antigen homolog is critical for the establishment of splenic latency. J. Virol. 77(19), 10295-10303 (2003).
82. Paden CR, Forrest JC, Moorman NJ, Speck SH. Murine gammaherpesvirus 68 LANA is essential for virus reactivation from splenocytes but not long-term carriage of viral genome. J. Virol. 84(14), 7214-7224 (2010).
83. Black J, Vos JM. Establishment of an oriP/ EBNA1-based episomal vector transcribing human genomic beta-globin in cultured murine fibroblasts. Gene Ther. 9(21), 1447-1454 (2002).
84. Yu J, Hu K, Smuga-Otto K et al. Human induced pluripotent stem cells free of vector and transgene sequences. Science 324(5928), 797-801 (2009).
85. Shioda T, Andriole S, Yahata T, Isselbacher KJ. A green fluorescent protein-reporter mammalian two-hybrid system with extrachromosomal maintenance of a prey expression plasmid: application to interaction screening. Proc. Natl Acad. Sci. USA 97(10), 5220-5224 (2000).
86. Lim C, Sohn H, Lee D, Gwack Y, Choe J. Functional dissection of latency-associated nuclear antigen 1 of Kaposis sarcoma-associated herpesvirus involved in latent DNA replication and transcription of terminal repeats of the viral genome. J. Virol. 76(20), 10320-10331 (2002).
87. Norio P, Schildkraut CL. Plasticity of DNA replication initiation in Epstein-Barr virus episomes. PLoS Biol. 2(6), e152 (2004).
88. Norio P, Schildkraut CL, Yates JL. 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(18), 8563-8574 (2000).
89. Verma SC, Lan K, Choudhuri T, Cotter MA, Robertson ES. An autonomous replicating element within the KSHV genome. Cell Host Microbe 2(2), 106-118 (2007).
90. Hu J, Garber AC, Renne R. The latency-associated nuclear antigen of Kaposis sarcoma-associated herpesvirus supports latent DNA replication in dividing cells. J. Virol. 76(22), 11677-11687 (2002).
91. Hung SC, Kang MS, Kieff E. Maintenance of Epstein-Barr virus (EBV) oriP-based 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(4), 1865-1870 (2001).
92. Shinohara H, Fukushi M, Higuchi M et al. Chromosome binding site of latency-associated nuclear antigen of Kaposis sarcoma-associated herpesvirus is essential for persistent episome maintenance and is functionally replaced by histone H1. J. Virol. 76(24), 12917-12924 (2002).
93. Verma SC, Choudhuri T, Robertson ES. The minimal replicator element of the Kaposis sarcoma-associated herpesvirus terminal repeat supports replication in a semiconservative and cell-cycle-dependent manner. J. Virol. 81(7), 3402-3413 (2007).
94. Kelley-Clarke B, Ballestas ME, Srinivasan V et al. Determination of Kaposis sarcoma-associated herpesvirus C-terminal latency-associated nuclear antigen residues mediating chromosome association and DNA binding. J. Virol. 81(8), 4348-4356 (2007).
95. Hu J, Liu E, Renne R. Involvement of SSRP1 in latent replication of Kaposis sarcoma-associated herpesvirus. J. Virol. 83(21), 11051-11063 (2009).
96. Winkler DD, Luger K. The histone chaperone fact: structural insights and mechanisms for nucleosome reorganization. J. Biol. Chem. 286(21), 18369-18374 (2011).
97. Sarek G, Jarviluoma A, Moore HM et al. Nucleophosmin phosphorylation by v-cyclin-CDK6 controls KSHV latency. PLoS Pathog. 6(3), e1000818 (2011).
98. Hong YK, Foreman K, Shin JW et al. Lymphatic reprogramming of blood vascular endothelium by Kaposi sarcoma-associated herpesvirus. Nat. Genet. 36(7), 683-685 (2004).
99. Moses AV, Fish KN, Ruhl R et al. Long-term infection and transformation of dermal microvascular endothelial cells by human herpesvirus 8. J. Virol. 73(8), 6892-6902 (1999).
100. Naranatt PP, Krishnan HH, Svojanovsky SR, Bloomer C, Mathur S, Chandran B. Host gene induction and transcriptional reprogramming in Kaposis sarcoma-associated herpesvirus (KSHV/HHV-8)-infected endothelial, fibroblast, and β cells: insights into modulation events early during infection. Cancer Res. 64(1), 72-84 (2004).
101. Poole LJ, Yu Y, Kim PS, Zheng QZ, Pevsner J, Hayward GS. Altered patterns of cellular gene expression in dermal microvascular endothelial cells infected with Kaposis sarcoma-associated herpesvirus. J. Virol. 76(7), 3395-3420 (2002).
102. Renne R, Barry C, Dittmer D, Compitello N, Brown PO, Ganem D. Modulation of cellular and viral gene expression by the latency-associated nuclear antigen of Kaposis sarcoma-associated herpesvirus. J. Virol. 75(1), 458-468 (2001).
103. Wang HW, Trotter MW, Lagos D et al. Kaposi sarcoma herpesvirus-induced cellular reprogramming contributes to the lymphatic endothelial gene expression in Kaposi sarcoma. Nat. Genet. 36(7), 687-693 (2004).
104. Wu W, Vieira J, Fiore N et al. KSHV/ HHV-8 infection of human hematopoietic progenitor (CD34+) cells: persistence of infection during hematopoiesis in vitro and in vivo. Blood 108(1), 141-151 (2006).
105. Carroll PA, Brazeau E, Lagunoff M. Kaposis sarcoma-associated herpesvirus infection of blood endothelial cells induces lymphatic differentiation. Virology 328(1), 7-18 (2004).
106. Hansen A, Henderson S, Lagos D et al. KSHV-encoded miRNAs target MAF to induce endothelial cell reprogramming. Genes Dev. 24(2), 195-205 (2010).
107. Shamay M, Krithivas A, Zhang J, Hayward SD. Recruitment of the de novo DNA methyltransferase Dnmt3a by Kaposis sarcoma-associated herpesvirus LANA. Proc. Natl Acad. Sci. USA 103(39), 14554-14559 (2006).
108. Jones PL, Wolffe AP. Relationships between chromatin organization and DNA methylation in determining gene expression. Semin. Cancer Biol. 9(5), 339-347 (1999).
109. Nakao M. Epigenetics: interaction of DNA methylation and chromatin. Gene 278(1-2), 25-31 (2001).
110. Wolffe AP, Matzke MA. Epigenetics: regulation through repression. Science 286(5439), 481-486 (1999).
111. Hermann A, Goyal R, Jeltsch A. The Dnmt1 DNA-(cytosine-C5)- methyltransferase methylates DNA processively with high preference for hemimethylated target sites. J. Biol. Chem. 279(46), 48350-48359 (2004).
112. Vertino PM, Sekowski JA, Coll JM et al. DNMT1 is a component of a multiprotein DNA replication complex. Cell Cycle 1(6), 416-423 (2002).
113. Okano M, Bell DW, Haber DA, Li E. DNA methyltransferases Dnmt3a and Dnmt3b are essential for de novo methylation and mammalian development. Cell 99(3), 247-257 (1999).
114. Di Bartolo DL, Cannon M, Liu YF et al. KSHV LANA inhibits TGF-beta signaling through epigenetic silencing of the TGF-beta type II receptor. Blood 111(9), 4731-4740 (2008).
115. An FQ, Compitello N, Horwitz E, Sramkoski M, Knudsen ES, Renne R. The latency-associated nuclear antigen of Kaposis sarcoma-associated herpesvirus modulates cellular gene expression and protects lymphoid cells from p16 INK4A-induced cell cycle arrest. J. Biol. Chem. 280(5), 3862-3874 (2005).
116. Ottinger M, Christalla T, Nathan K, Brinkmann MM, Viejo-Borbolla A, Schulz TF. Kaposis 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(21), 10772-10786 (2006).
117. Roupelieva M, Griffiths SJ, Kremmer E et al. Kaposis sarcoma-associated herpesvirus Lana-1 is a major activator of the serum response element and mitogen-activated protein kinase pathways via interactions with the Mediator complex. J. Gen. Virol. 91(Pt 5), 1138-1149 (2010).
118. Tang J, Gordon GM, Muller MG, Dahiya M, Foreman KE. Kaposis sarcoma-associated herpesvirus latency-associated nuclear antigen induces expression of the helix-loop-helix protein Id-1 in human endothelial cells. J. Virol. 77(10), 5975-5984 (2003).
119. Verma SC, Borah S, Robertson ES. Latency-associated nuclear antigen of Kaposis sarcoma-associated herpesvirus up-regulates transcription of human telomerase reverse transcriptase promoter through interaction with transcription factor Sp1. J. Virol. 78(19), 10348-10359 (2004).
120. Viejo-Borbolla A, Ottinger M, Bruning E et al. Brd2/RING3 interacts with a chromatin-binding domain in the Kaposis Sarcoma-associated herpesvirus latency-associated nuclear antigen 1 (LANA-1) that is required for multiple functions of LANA-1. J. Virol. 79(21), 13618-13629 (2005).
121. Jeong JH, Orvis J, Kim JW, Mcmurtrey CP, Renne R, Dittmer DP. Regulation and autoregulation of the promoter for the latency-associated nuclear antigen of Kaposis sarcoma-associated herpesvirus. J. Biol. Chem. 279(16), 16822-16831 (2004).
122. Dewire SM, Damania B. The latency-associated nuclear antigen of rhesus monkey rhadinovirus inhibits viral replication through repression of Orf50/Rta transcriptional activation. J. Virol. 79(5), 3127-3138 (2005).
123. Lan K, Kuppers DA, Verma SC, Robertson ES. Kaposis sarcoma-associated herpesvirus-encoded latency-associated nuclear antigen inhibits lytic replication by targeting Rta: a potential mechanism for virus-mediated control of latency. J. Virol. 78(12), 6585-6594 (2004).
124. An J, Sun Y, Rettig MB. Transcriptional coactivation of c-Jun by the KSHV-encoded LANA. Blood 103(1), 222-228 (2004).
125. Bubman D, Guasparri I, Cesarman E. Deregulation of c-Myc in primary effusion lymphoma by Kaposis sarcoma herpesvirus latency-associated nuclear antigen. Oncogene 26(34), 4979-4986 (2007).
126. Cai Q, Lan K, Verma SC, Si H, Lin D, Robertson ES. Kaposis sarcoma-associated herpesvirus latent protein LANA interacts with HIF-1 alpha to upregulate RTA expression during hypoxia: latency control under low oxygen conditions. J. Virol. 80(16), 7965-7975 (2006).
127. Hyun TS, Subramanian C, Cotter MA, 2nd, Thomas RA, Robertson ES. Latency-associated nuclear antigen encoded by Kaposis sarcoma-associated herpesvirus interacts with Tat and activates the long terminal repeat of human immunodeficiency virus type 1 in human cells. J. Virol. 75(18), 8761-8771 (2001).
128. Lim C, Gwack Y, Hwang S, Kim S, Choe J. The transcriptional activity of cAMP response element-binding protein-binding protein is modulated by the latency associated nuclear antigen of Kaposis sarcoma-associated herpesvirus. J. Biol. Chem. 276(33), 31016-31022 (2001).
129. Lim C, Sohn H, Gwack Y, Choe J. Latency-associated nuclear antigen of Kaposis sarcoma-associated herpesvirus (human herpesvirus-8) binds ATF4/CREB2 and inhibits its transcriptional activation activity. J. Gen. Virol. 81(Pt 11), 2645-2652 (2000).
130. Liu J, Martin HJ, Liao G, Hayward SD. The Kaposis sarcoma-associated herpesvirus LANA protein stabilizes and activates c-Myc. J. Virol. 81(19), 10451-10459 (2007).
131. Muromoto R, Okabe K, Fujimuro M et al. Physical and functional interactions between STAT3 and Kaposis sarcoma-associated herpesvirus-encoded LANA. FEBS Lett. 580(1), 93-98 (2006).
132. Pan HY, Zhang YJ, Wang XP, Deng JH, Zhou FC, Gao SJ. Identification of a novel cellular transcriptional repressor interacting with the latent nuclear antigen of Kaposis sarcoma-associated herpesvirus. J. Virol. 77(18), 9758-9768 (2003).
133. Radkov SA, Kellam P, Boshoff C. The latent nuclear antigen of Kaposi sarcoma-associated herpesvirus targets the retinoblastoma-E2F pathway and with the oncogene Hras transforms primary rat cells. Nat. Med. 6(10), 1121-1127 (2000).
134. Watanabe A, Higuchi M, Fukushi M et al. A novel KRAB-Zinc finger protein interacts with latency-associated nuclear antigen of Kaposis sarcoma-associated herpesvirus and activates transcription via terminal repeat sequences. Virus Genes 34(2), 127-136 (2007).
135. Kusano S, Eizuru Y. Human I-mfa domain proteins specifically interact with KSHV LANA and affect its regulation of Wnt signaling-dependent transcription. Biochem. Biophys. Res. Commun. 396(3), 608-613 (2010).
136. Lan K, Kuppers DA, Robertson ES. Kaposis sarcoma-associated herpesvirus reactivation is regulated by interaction of latency-associated nuclear antigen with recombination signal sequence-binding protein Jkappa, the major downstream effector of the Notch signaling pathway. J. Virol. 79(6), 3468-3478 (2005).
137. Lim C, Seo T, Jung J, Choe J. Identification of a virus trans-acting regulatory element on the latent DNA replication of Kaposis sarcoma-associated herpesvirus. J. Gen. Virol. 85(Pt 4), 843-855 (2004).
138. Si H, Robertson ES. Kaposis sarcoma-associated herpesvirus-encoded latency-associated nuclear antigen induces chromosomal instability through inhibition of p53 function. J. Virol. 80(2), 697-709 (2006).
139. Watanabe T, Sugaya M, Atkins AM et al. Kaposis sarcoma-associated herpesvirus latency-associated nuclear antigen prolongs the life span of primary human umbilical vein endothelial cells. J. Virol. 77(11), 6188-6196 (2003).
140. Wong LY, Matchett GA, Wilson AC. Transcriptional activation by the Kaposis sarcoma-associated herpesvirus latency-associated nuclear antigen is facilitated by an N-terminal chromatin-binding motif. J. Virol. 78(18), 10074-10085 (2004).
141. Borah S, Verma SC, Robertson ES. ORF73 of herpesvirus saimiri, a viral homolog of Kaposis sarcoma-associated herpesvirus, modulates the two cellular tumor suppressor proteins p53 and pRb. J. Virol. 78(19), 10336-10347 (2004).
142. Cai Q, Murakami M, Si H, Robertson ES. A potential alpha-helix motif in the amino terminus of LANA encoded by Kaposis sarcoma-associated herpesvirus is critical for nuclear accumulation of HIF-1alpha in normoxia. J. Virol. 81(19), 10413-10423 (2007).
143. Friborg J Jr, Kong W, Hottiger MO, Nabel GJ. p53 inhibition by the LANA protein of KSHV protects against cell death. Nature 402(6764), 889-894 (1999).
144. Katano H, Sato Y, Sata T. Expression of p53 and human herpesvirus-8 (HHV-8)-encoded latency-associated nuclear antigen with inhibition of apoptosis in HHV-8-associated malignancies. Cancer 92(12), 3076-3084 (2001).
145. Boulanger E, Marchio A, Hong SS, Pineau P. Mutational analysis of TP53, PTEN, PIK3CA and CTNNB1/beta-catenin genes in human herpesvirus 8-associated primary effusion lymphoma. Haematologica 94(8), 1170-1174 (2009).
146. Carbone A, Cilia AM, Gloghini A et al. Characterization of a novel HHV-8-positive cell line reveals implications for the pathogenesis and cell cycle control of primary effusion lymphoma. Leukemia 14(7), 1301-1309 (2000).
147. Chen W, Hilton IB, Staudt MR, Burd CE, Dittmer DP. Distinct p53, p53:LANA, and LANA complexes in Kaposis Sarcoma-associated Herpesvirus Lymphomas. J. Virol. 84(8), 3898-3908 (2010).
148. Kennedy MM, Lucas SB, Jones RR et al. HHV8 and Kaposis sarcoma: a time cohort study. Mol. Pathol. 50(2), 96-100 (1997).
149. Petre CE, Sin SH, Dittmer DP. Functional p53 signaling in Kaposis sarcoma-associated herpesvirus lymphomas: implications for therapy. J. Virol. 81(4), 1912-1922 (2007).
150. Sarek G, Kurki S, Enback J et al. Reactivation of the p53 pathway as a treatment modality for KSHV-induced lymphomas. J. Clin. Invest. 117(4), 1019-1028 (2007).
151. Fakhari FD, Jeong JH, Kanan Y, Dittmer DP. The latency-associated nuclear antigen of Kaposi sarcoma-associated herpesvirus induces β cell hyperplasia and lymphoma. J. Clin. Invest. 116(3), 735-742 (2006).
152. Jeong JH, Hines-Boykin R, Ash JD, Dittmer DP. Tissue specificity of the Kaposis sarcoma-associated herpesvirus latent nuclear antigen (LANA/orf73) promoter in transgenic mice. J. Virol. 76(21), 11024-11032 (2002).
153. Sin SH, Fakhari FD, Dittmer DP. The viral latency-associated nuclear antigen augments the B-cell response to antigen in vivo. J. Virol. 84(20), 10653-10660 (2010).
154. Fujimuro M, Hayward SD. The latency-associated nuclear antigen of Kaposis sarcoma-associated herpesvirus manipulates the activity of glycogen synthase kinase-3beta. J. Virol. 77(14), 8019-8030 (2003).
155. Fujimuro M, Hayward SD. Manipulation of glycogen-synthase kinase-3 activity in KSHV-associated cancers. J. Mol. Med. 82(4), 223-231 (2004).
156. Fujimuro M, Liu J, Zhu J, Yokosawa H, Hayward SD. Regulation of the interaction between glycogen synthase kinase 3 and the Kaposis sarcoma-associated herpesvirus latency-associated nuclear antigen. J. Virol. 79(16), 10429-10441 (2005).
157. Fujimuro M, Wu FY, Aprhys C et al. A novel viral mechanism for dysregulation of beta-catenin in Kaposis sarcoma-associated herpesvirus latency. Nat. Med. 9(3), 300-306 (2003).
158. Hagen T. Characterization of the interaction between latency-associated
159. Lu J, Verma SC, Murakami M et al. Latency-associated nuclear antigen of Kaposis sarcoma-associated herpesvirus (KSHV) upregulates survivin expression in KSHV-Associated B-lymphoma cells and contributes to their proliferation. J. Virol. 83(14), 7129-7141 (2009).
160. Cheng F, Weidner-Glunde M, Varjosalo M et al. KSHV reactivation from latency requires Pim-1 and Pim-3 kinases to inactivate the latency-associated nuclear antigen LANA. PLoS Pathog. 5(3), e1000324 (2009).
161. Bajaj BG, Verma SC, Lan K, Cotter MA, Woodman ZL, Robertson ES. KSHV encoded LANA upregulates Pim-1 and is a substrate for its kinase activity. Virology 351(1), 18-28 (2006).
162. Delgado T, Carroll PA, Punjabi AS, Margineantu D, Hockenbery DM, Lagunoff M. Induction of the Warburg effect by Kaposis sarcoma herpesvirus is required for the maintenance of latently infected endothelial cells. Proc. Natl Acad. Sci. USA 107(23), 10696-10701 (2010).
163. Cai QL, Knight JS, Verma SC, Zald P, Robertson ES. EC5S ubiquitin complex is recruited by KSHV latent antigen LANA for degradation of the VHL and p53 tumor suppressors. PLoS Pathog. 2(10), e116 (2006).
164. Rodrigues L, Filipe J, Seldon MP et al. Termination of NF-kappaB activity through a gammaherpesvirus protein that assembles an EC5S ubiquitin-ligase. EMBO J. 28(9), 1283-1295 (2009).
165. Ottinger M, Pliquet D, Christalla T, Frank R, Stewart JP, Schulz TF. The interaction of the gammaherpesvirus 68 orf73 protein with cellular BET proteins affects the activation of cell cycle promoters. J. Virol. 83(9), 4423-4434 (2009).
166. You J, Srinivasan V, Denis GV et al. Kaposis sarcoma-associated herpesvirus latency-associated nuclear antigen interacts with bromodomain protein Brd4 on host mitotic chromosomes. J. Virol. 80(18), 8909-8919 (2006).
167. Dey A, Nishiyama A, Karpova T, Mcnally J, Ozato K. Brd4 marks select genes on mitotic chromatin and directs postmitotic transcription. Mol. Biol. Cell 20(23), 4899-4909 (2009).
168. French CA, Miyoshi I, Aster JC et al. BRD4 bromodomain gene rearrangement in aggressive carcinoma with translocation t(15;19). Am. J. Pathol. 159(6), 1987-1992 (2001).
169. French CA, Miyoshi I, Kubonishi I, Grier HE, Perez-Atayde AR, Fletcher JA. BRD4-NUT fusion oncogene: a novel mechanism in aggressive carcinoma. Cancer Res. 63(2), 304-307 (2003).
170. Huang B, Yang XD, Zhou MM, Ozato K, Chen LF. Brd4 coactivates transcriptional activation of NF-kappaB via specific binding to acetylated RelA. Mol. Cell Biol. 29(5), 1375-1387 (2009).
171. Maruyama T, Farina A, Dey A et al. A Mammalian bromodomain protein, brd4, interacts with replication factor C and inhibits progression to S phase. Mol. Cell Biol. 22(18), 6509-6520 (2002).
172. Mochizuki K, Nishiyama A, Jang MK et al. The bromodomain protein Brd4 stimulates G1 gene transcription and promotes progression to S phase. J. Biol. Chem. 283(14), 9040-9048 (2008).
173. Jang MK, Kwon D, Mcbride AA. Papillomavirus E2 proteins and the host BRD4 protein associate with transcriptionally active cellular chromatin. J. Virol. 83(6), 2592-2600 (2009).
174. Lin A, Wang S, Nguyen T, Shire K, Frappier L. The EBNA1 protein of Epstein-Barr virus functionally interacts with Brd4. J. Virol. 82(24), 12009-12019 (2008).
175. Mcphillips MG, Ozato K, Mcbride AA. Interaction of bovine papillomavirus E2 protein with Brd4 stabilizes its association with chromatin. J. Virol. 79(14), 8920-8932 (2005).
176. Senechal H, Poirier GG, Coulombe B, Laimins LA, Archambault J. Amino acid substitutions that specifically impair the transcriptional activity of papillomavirus E2 affect binding to the long isoform of Brd4. Virology 358(1), 10-17 (2007).
177. Murakami Y, Yamagoe S, Noguchi K et al. Ets-1-dependent expression of vascular endothelial growth factor receptors is activated by latency-associated nuclear antigen of Kaposis sarcoma-associated herpesvirus through interaction with Daxx. J. Biol. Chem. 281(38), 28113-28121 (2006).
178. Verma SC, Bajaj BG, Cai Q, Si H, Seelhammer T, Robertson ES. Latency-associated nuclear antigen of Kaposis sarcoma-associated herpesvirus recruits uracil DNA glycosylase 2 at the terminal repeats and is important for latent persistence of the virus. J. Virol. 80(22), 11178-11190 (2006).
179. Lan K, Verma SC, Murakami M, Bajaj B, Kaul R, Robertson ES. Kaposis sarcoma herpesvirus-encoded latency-associated nuclear antigen stabilizes intracellular activated Notch by targeting the Sel10 protein. Proc. Natl Acad. Sci. USA 104(41), 16287-16292 (2007).
180. Sakakibara S, Ueda K, Nishimura K et al. Accumulation of heterochromatin components on the terminal repeat sequence of Kaposis sarcoma-associated herpesvirus mediated by the latency-associated nuclear antigen. J. Virol. 78(14), 7299-7310 (2004).
181. Fukushi M, Higuchi M, Oie M et al. Latency-associated nuclear antigen of Kaposis sarcoma-associated herpesvirus interacts with human myeloid cell nuclear differentiation antigen induced by interferon alpha. Virus Genes 27(3), 237-247 (2003).
182. Si H, Verma SC, Lampson MA, Cai Q, Robertson ES. Kaposis sarcoma-associated herpesvirus-encoded LANA can interact with the nuclear mitotic apparatus protein to regulate genome maintenance and segregation. J. Virol. 82(13), 6734-6746 (2008).