About this Journal Submit a Manuscript Table of Contents
Advances in Virology
Volume 2011 (2011), Article ID 193860, 19 pages
http://dx.doi.org/10.1155/2011/193860
Review Article

Mechanisms of Kaposi's Sarcoma-Associated Herpesvirus Latency and Reactivation

Fengchun Ye,1,2,3 Xiufen Lei,1,2,3 and Shou-Jiang Gao1,2,3

1Tumor Virology Program, Greehey Children's Cancer Research Institute, The University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA
2Department of Pediatrics, The University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA
3Cancer Therapy and Research Center, The University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA

Received 16 November 2010; Revised 6 March 2011; Accepted 7 March 2011

Academic Editor: Eric O. Freed

Copyright © 2011 Fengchun Ye et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. Y. Chang, E. Cesarman, M. S. Pessin et al., “Identification of herpesvirus-like DNA sequences in AIDS-associated Kaposi's sarcoma,” Science, vol. 266, no. 5192, pp. 1865–1869, 1994. View at Scopus
  2. R. Sarid and S. J. Gao, “Viruses and human cancer: from detection to causality,” Cancer Letters, vol. 305, no. 2, pp. 218–227, 2011.
  3. C. Boshoff, “Kaposi's sarcoma biology,” IUBMB Life, vol. 53, no. 4-5, pp. 259–261, 2002. View at Publisher · View at Google Scholar · View at Scopus
  4. E. Cesarman, Y. Chang, P. S. Moore, J. W. Said, and D. M. Knowles, “Kaposi's sarcoma-associated herpesvirus-like DNA sequences in AIDS- related body-cavity-based lymphomas,” The New England Journal of Medicine, vol. 332, no. 18, pp. 1186–1191, 1995. View at Publisher · View at Google Scholar · View at Scopus
  5. E. Cesarman, R. G. Nador, K. Aozasa, G. Delsol, J. W. Said, and D. M. Knowles, “Kaposi's sarcoma-associated herpesvirus in non-AIDS-related lymphomas occurring in body cavities,” American Journal of Pathology, vol. 149, no. 1, pp. 53–57, 1996. View at Scopus
  6. J. Soulier, L. Grollet, E. Oksenhendler et al., “Kaposi's sarcoma-associated herpesvirus-like DNA sequences in multicentric Castleman's disease,” Blood, vol. 86, no. 4, pp. 1276–1280, 1995. View at Scopus
  7. C. Boshoff and Y. Chang, “Kaposi's sarcoma-associated herpesvirus: a new DNA tumor virus,” Annual Review of Medicine, vol. 52, pp. 453–470, 2001. View at Publisher · View at Google Scholar · View at Scopus
  8. D. M. Ciufo, J. S. Cannon, L. J. Poole et al., “Spindle cell conversion by Kaposi's sarcoma-associated herpesvirus: formation of colonies and plaques with mixed lytic and latent gene expression in infected primary dermal microvascular endothelial cell cultures,” Journal of Virology, vol. 75, no. 12, pp. 5614–5626, 2001. View at Publisher · View at Google Scholar · View at Scopus
  9. S. J. Gao, J. H. Deng, and F. U. C. Zhou, “Productive lytic replication of a recombinant Kaposi's sarcoma-associated herpesvirus in efficient primary infection of primary human endothelial cells,” Journal of Virology, vol. 77, no. 18, pp. 9738–9749, 2003. View at Publisher · View at Google Scholar · View at Scopus
  10. H. Pan, F. Zhou, and S. J. Gao, “Kaposi's sarcoma-associated herpesvirus induction of chromosome instability in primary human endothelial cells,” Cancer Research, vol. 64, no. 12, pp. 4064–4068, 2004. View at Publisher · View at Google Scholar · View at Scopus
  11. H. W. Wang, M. W. B. Trotter, D. Lagos et al., “Kaposi sarcoma herpesvirus-induced cellular reprogramming contributes to the lymphatic endothelial gene expression in Kaposi sarcoma,” Nature Genetics, vol. 36, no. 7, pp. 687–693, 2004. View at Publisher · View at Google Scholar · View at Scopus
  12. Y. K. Hong, K. Foreman, J. W. Shin et al., “Lymphatic reprogramming of blood vascular endothelium by Kaposi sarcoma-associated herpesvirus,” Nature Genetics, vol. 36, no. 7, pp. 683–685, 2004. View at Publisher · View at Google Scholar · View at Scopus
  13. P. A. Carroll, E. Brazeau, and M. Lagunoff, “Kaposi's sarcoma-associated herpesvirus infection of blood endothelial cells induces lymphatic differentiation,” Virology, vol. 328, no. 1, pp. 7–18, 2004. View at Publisher · View at Google Scholar · View at Scopus
  14. L. I. W. Qian, J. Xie, F. Ye, and S. J. Gao, “Kaposi's sarcoma-associated herpesvirus infection promotes invasion of primary human umbilical vein endothelial cells by inducing matrix metalloproteinases,” Journal of Virology, vol. 81, no. 13, pp. 7001–7010, 2007. View at Publisher · View at Google Scholar · View at Scopus
  15. F. C. Ye, D. J. Blackbourn, M. Mengel et al., “Kaposi's sarcoma-associated herpesvirus promotes angiogenesis by inducing angiopoietin-2 expression via AP-1 and Ets1,” Journal of Virology, vol. 81, no. 8, pp. 3980–3991, 2007. View at Publisher · View at Google Scholar · View at Scopus
  16. L. I. W. Qian, W. Greene, F. Ye, and S. J. Gao, “Kaposi's sarcoma-associated herpesvirus disrupts adherens junctions and increases endothelial permeability by inducing degradation of VE-cadherin,” Journal of Virology, vol. 82, no. 23, pp. 11902–11912, 2008. View at Publisher · View at Google Scholar · View at Scopus
  17. P. P. Naranatt, H. H. Krishnan, S. R. Svojanovsky, C. Bloomer, S. Mathur, and B. Chandran, “Host gene induction and transcriptional reprogramming in Kaposi's sarcoma-associated herpesvirus (KSHV/HHV-8)-infected endothelial, fibroblast, and B cells: insights into modulation events early during infection,” Cancer Research, vol. 64, no. 1, pp. 72–84, 2004. View at Publisher · View at Google Scholar · View at Scopus
  18. N. Sharma-Walia, H. Raghu, S. Sadagopan et al., “Cyclooxygenase 2 induced by Kaposi's sarcoma-associated herpesvirus early during in vitro infection of target cells plays a role in the maintenance of latent viral gene expression,” Journal of Virology, vol. 80, no. 13, pp. 6534–6552, 2006. View at Publisher · View at Google Scholar · View at Scopus
  19. S. Sadagopan, N. Sharma-Walia, M. V. Veettil et al., “Kaposi's sarcoma-associated herpesvirus induces sustained NF-κB activation during de novo infection of primary human dermal microvascular endothelial cells that is essential for viral gene expression,” Journal of Virology, vol. 81, no. 8, pp. 3949–3968, 2007. View at Publisher · View at Google Scholar · View at Scopus
  20. A. M. Cattelan, M. L. Calabrò, A. De Rossi et al., “Long-term clinical outcome of AIDS-related Kaposi's sarcoma during highly active antiretroviral therapy,” International Journal of Oncology, vol. 27, no. 3, pp. 779–785, 2005. View at Scopus
  21. A. M. Cattelan, M. L. Calabrò, P. Gasperini et al., “Acquired immunodeficiency syndrome-related Kaposi's sarcoma regression after highly active antiretroviral therapy: biologic correlates of clinical outcome,” Journal of the National Cancer Institute. Monographs, no. 28, pp. 44–49, 2001. View at Scopus
  22. C. Pellet, D. Kerob, A. Dupuy et al., “Kaposi's sarcoma-associated herpesvirus viremia is associated with the progression of classic and endemic Kaposi's sarcoma,” Journal of Investigative Dermatology, vol. 126, no. 3, pp. 621–627, 2006. View at Publisher · View at Google Scholar · View at Scopus
  23. R. Duprez, E. Kassa-Kelembho, S. Plancoulaine et al., “Human herpesvirus 8 serological markers and viral load in patients with AIDS-associated Kaposi's sarcoma in Central African Republic,” Journal of Clinical Microbiology, vol. 43, no. 9, pp. 4840–4843, 2005. View at Publisher · View at Google Scholar · View at Scopus
  24. E. Guttman-Yassky, R. Abada, Z. Kra-Oz et al., “Relationship between human herpesvirus 8 loads and disease stage in classic Kaposi sarcoma patients,” Diagnostic Microbiology and Infectious Disease, vol. 57, no. 4, pp. 387–392, 2007. View at Publisher · View at Google Scholar · View at Scopus
  25. A. G. Marcelin, J. Motol, A. Guihot et al., “Relationship between the quantity of Kaposi sarcoma-associated herpesvirus (KSHV) in peripheral blood and effusion fluid samples and KSHV-associated disease,” Journal of Infectious Diseases, vol. 196, no. 8, pp. 1163–1166, 2007. View at Publisher · View at Google Scholar · View at Scopus
  26. J. Song, A. Yoshida, Y. Yamamoto et al., “Viral load of human herpesvirus 8 (HHV-8) in the circulatory blood cells correlates with clinical progression in a patient with HHV-8-associated solid lymphoma with AIDS-associated Kaposi's sarcoma,” Leukemia and Lymphoma, vol. 45, no. 11, pp. 2343–2347, 2004. View at Publisher · View at Google Scholar · View at Scopus
  27. M. Guadalupe, B. H. Pollock, S. Westbrook et al., “Risk factors influencing antibody responses to kaposi's sarcoma-associated herpesvirus latent and lytic antigens in patients under antiretroviral therapy,” Journal of Acquired Immune Deficiency Syndromes, vol. 56, no. 1, pp. 83–90, 2011. View at Publisher · View at Google Scholar
  28. J. L. Jones, D. L. Hanson, S. Y. Chu, J. W. Ward, and H. W. Jaffe, “AIDS-associated Kaposi's sarcoma,” Science, vol. 267, no. 5201, pp. 1077–1078, 1995. View at Scopus
  29. A. Mocroft, M. Youle, B. Gazzard, et al., “Anti-herpesvirus treatment and risk of Kaposi's sarcoma in HIV infection. Royal Free/Chelsea and Westminster Hospitals Collaborative Group,” AIDS, vol. 10, no. 10, pp. 1101–1105, 1996.
  30. D. F. Martin, B. D. Kuppermann, R. A. Wolitz, A. G. Palestine, H. Li, and C. A. Robinson, “Oral ganciclovir for patients with cytomegalovirus retinitis treated with a ganciclovir implant,” The New England Journal of Medicine, vol. 340, no. 14, pp. 1063–1070, 1999. View at Publisher · View at Google Scholar
  31. S. Hwang, T. T. Wu, L. M. Tong et al., “Persistent gammaherpesvirus replication and dynamic interaction with the host in vivo,” Journal of Virology, vol. 82, no. 24, pp. 12498–12509, 2008. View at Publisher · View at Google Scholar · View at Scopus
  32. S. T. Perry and T. Compton, “Kaposi's sarcoma-associated herpesvirus virions inhibit interferon responses induced by envelope glycoprotein gpK8.1,” Journal of Virology, vol. 80, no. 22, pp. 11105–11114, 2006. View at Publisher · View at Google Scholar · View at Scopus
  33. P. Monini, F. Carlini, M. Stürzl et al., “Alpha interferon inhibits human herpesvirus 8 (HHV-8) reactivation in primary effusion lymphoma cells and reduces HHV-8 load in cultured peripheral blood mononuclear cells,” Journal of Virology, vol. 73, no. 5, pp. 4029–4041, 1999. View at Scopus
  34. J. Chang, R. Renne, D. Dittmer, and D. Ganem, “Inflammatory cytokines and the reactivation of Kaposi's sarcoma- associated herpesvirus lytic replication,” Virology, vol. 266, no. 1, pp. 17–25, 2000. View at Publisher · View at Google Scholar · View at Scopus
  35. M. Chatterjee, J. Osborne, G. Bestetti, Y. Chang, and P. S. Moore, “Viral IL-6-induced cell proliferation and immune evasion of interferon activity,” Science, vol. 298, no. 5597, pp. 1432–1435, 2002. View at Publisher · View at Google Scholar · View at Scopus
  36. V. P. Pozharskaya, L. L. Weakland, J. C. Zimring et al., “Short duration of elevated vIRF-1 expression during lytic replication of human herpesvirus 8 limits its ability to block antiviral responses induced by alpha interferon in BCBL-1 cells,” Journal of Virology, vol. 78, no. 12, pp. 6621–6635, 2004. View at Publisher · View at Google Scholar · View at Scopus
  37. V. P. Pozharskaya, L. L. Weakland, and M. K. Offermann, “Inhibition of infectious human herpesvirus 8 production by gamma interferon and alpha interferon in BCBL-1 cells,” Journal of General Virology, vol. 85, no. 10, pp. 2779–2787, 2004. View at Publisher · View at Google Scholar · View at Scopus
  38. L. T. Krug, V. P. Pozharskaya, Y. Yu, N. Inoue, and M. K. Offermann, “Inhibition of infection and replication of human herpesvirus 8 in microvascular endothelial cells by alpha interferon and phosphonoformic acid,” Journal of Virology, vol. 78, no. 15, pp. 8359–8371, 2004. View at Publisher · View at Google Scholar · View at Scopus
  39. J. Wang, J. Zhang, L. Zhang, W. Harrington, J. T. West, and C. Wood, “Modulation of human herpesvirus 8/Kaposi's sarcoma-associated herpesvirus replication and transcription activator transactivation by interferon regulatory factor 7,” Journal of Virology, vol. 79, no. 4, pp. 2420–2431, 2005. View at Publisher · View at Google Scholar · View at Scopus
  40. T. Zhang, Y. Wang, L. Zhang et al., “Lysine residues of interferon regulatory factor 7 affect the replication and transcription activator-mediated lytic replication of Kaposi's sarcoma-associated herpesvirus/human herpesvirus 8,” Journal of General Virology, vol. 92, no. 1, pp. 181–187, 2011. View at Publisher · View at Google Scholar
  41. I. Tempera and P. M. Lieberman, “Chromatin organization of gammaherpesvirus latent genomes,” Biochimica et Biophysica Acta, vol. 1799, no. 3-4, pp. 236–245, 2010. View at Publisher · View at Google Scholar · View at Scopus
  42. S. N. Pantry and P. G. Medveczky, “Epigenetic regulation of Kaposi's sarcoma-associated herpesvirus replication,” Seminars in Cancer Biology, vol. 19, no. 3, pp. 153–157, 2009. View at Publisher · View at Google Scholar · View at Scopus
  43. F. Lu, L. Day, S. J. Gao, and P. M. Lieberman, “Acetylation of the latency-associated nuclear antigen regulates repression of Kaposi's sarcoma-associated herpesvirus lytic transcription,” Journal of Virology, vol. 80, no. 11, pp. 5273–5282, 2006. View at Publisher · View at Google Scholar · View at Scopus
  44. T. Günther and A. Grundhoff, “The epigenetic landscape of latent kaposi sarcoma-associated herpesvirus genomes,” PLoS Pathogens, vol. 6, no. 6, Article ID e1000935, 2010. View at Publisher · View at Google Scholar
  45. Z. Toth, D. T. Maglinte, S. H. Lee et al., “Epigenetic analysis of KSHV latent and lytic genomes,” PLoS Pathogens, vol. 6, no. 7, Article ID e1001013, 2010. View at Publisher · View at Google Scholar
  46. D. Dittmer, M. Lagunoff, R. Renne, K. Staskus, A. Haase, and D. Ganem, “A cluster of latently expressed genes in Kaposi's sarcoma-associated herpesvirus,” Journal of Virology, vol. 72, no. 10, pp. 8309–8315, 1998. View at Scopus
  47. J. L. Umbach and B. R. Cullen, “In-depth analysis of Kaposi's sarcoma-associated herpesvirus microrna expression provides insights into the mammalian microRNA-processing machinery,” Journal of Virology, vol. 84, no. 2, pp. 695–703, 2010. View at Publisher · View at Google Scholar · View at Scopus
  48. H. Kang and P. M. Lieberman, “Cell cycle control of Kaposi's sarcoma-associated herpesvirus latency transcription by CTCF-cohesin interactions,” Journal of Virology, vol. 83, no. 12, pp. 6199–6210, 2009. View at Publisher · View at Google Scholar · View at Scopus
  49. W. Stedman, H. Kang, S. Lin, J. L. Kissil, M. S. Bartolomei, and P. M. Lieberman, “Cohesins localize with CTCF at the KSHV latency control region and at cellular c-myc and H19/Igf2 insulators,” The EMBO Journal, vol. 27, no. 4, pp. 654–666, 2008. View at Publisher · View at Google Scholar · View at Scopus
  50. S. J. Gao, L. Kingsley, D. R. Hoover et al., “Seroconversion to antibodies against Kaposi's sarcoma-associated herpesvirus-related latent nuclear antigens before the development of Kaposi's sarcoma,” The New England Journal of Medicine, vol. 335, no. 4, pp. 233–241, 1996. View at Publisher · View at Google Scholar · View at Scopus
  51. S. J. Gao, L. Kingsley, M. Li et al., “KSHV antibodies among Americans, Italians and Ugandans with and without Kaposi's sarcoma,” Nature Medicine, vol. 2, no. 8, pp. 925–927, 1996. View at Publisher · View at Google Scholar · View at Scopus
  52. D. H. Kedes, E. Operskalski, M. Busch, R. Kohn, J. Flood, and D. Ganem, “The seroepidemiology of human herpesvirus 8 (Kaposi's sarcoma-associated herpesvirus): distribution of infection in KS risk groups and evidence for sexual transmission,” Nature Medicine, vol. 2, no. 8, pp. 918–924, 1996. View at Publisher · View at Google Scholar · View at Scopus
  53. S. J. Gao, Y. J. Zhang, J. H. Deng, C. S. Rabkin, O. Flore, and H. B. Jenson, “Molecular polymorphism of Kaposi's sarcoma-associated herpesvirus (human herpesvirus 8) latent nuclear antigen: evidence for a large repertoire of viral genotypes and dual infection with different viral genotypes,” Journal of Infectious Diseases, vol. 180, no. 5, pp. 1466–1476, 1999. View at Publisher · View at Google Scholar · View at Scopus
  54. L. Rainbow, G. M. Platt, G. R. Simpson et al., “The 222- to 234-kilodalton latent nuclear protein (LNA) of Kaposi's sarcoma-associated herpesvirus (human herpesvirus 8) is encoded by orf73 and is a component of the latency-associated nuclear antigen,” Journal of Virology, vol. 71, no. 8, pp. 5915–5921, 1997. View at Scopus
  55. M. E. Ballestas, P. A. Chatis, and K. M. Kaye, “Efficient persistence of extrachromosomal KSHV DNA mediated by latency- associated nuclear antigen,” Science, vol. 284, no. 5414, pp. 641–644, 1999. View at Publisher · View at Google Scholar · View at Scopus
  56. M. A. Cotter and E. S. Robertson, “The latency-associated nuclear antigen tethers the Kaposi's sarcoma- associated herpesvirus genome to host chromosomes in body cavity-based lymphoma cells,” Virology, vol. 264, no. 2, pp. 254–264, 1999. View at Publisher · View at Google Scholar · View at Scopus
  57. J. Hu, A. C. Garber, and R. Renne, “The latency-associated nuclear antigen of Kaposi's sarcoma-associated herpesvirus supports latent DNA replication in dividing cells,” Journal of Virology, vol. 76, no. 22, pp. 11677–11687, 2002. View at Publisher · View at Google Scholar · View at Scopus
  58. H. Si, S. C. Verma, M. A. Lampson, Q. Cai, and E. S. Robertson, “Kaposi's sarcoma-associated herpesvirus-encoded LANA can interact with the nuclear mitotic apparatus protein to regulate genome maintenance and segregation,” Journal of Virology, vol. 82, no. 13, pp. 6734–6746, 2008. View at Publisher · View at Google Scholar · View at Scopus
  59. M. A. Cotter, C. Subramanian, and E. S. Robertson, “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, vol. 291, no. 2, pp. 241–259, 2001. View at Publisher · View at Google Scholar · View at Scopus
  60. M. E. Ballestas and K. M. Kaye, “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,” Journal of Virology, vol. 75, no. 7, pp. 3250–3258, 2001. View at Publisher · View at Google Scholar · View at Scopus
  61. A. C. Garber, M. A. Shu, J. Hu, and R. Renne, “DNA binding and modulation of gene expression by the latency-associated nuclear antigen of Kaposi's sarcoma-associated herpesvirus,” Journal of Virology, vol. 75, no. 17, pp. 7882–7892, 2001. View at Publisher · View at Google Scholar · View at Scopus
  62. G. Fejér, M. M. Medveczky, E. Horvath, B. Lane, Y. Chang, and P. G. Medveczky, “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,” Journal of General Virology, vol. 84, no. 6, pp. 1451–1462, 2003. View at Publisher · View at Google Scholar · View at Scopus
  63. A. Grundhoff and D. Ganem, “The latency-associated nuclear antigen of Kaposi's sarcoma-associated herpesvirus permits replication of terminal repeat-containing plasmids,” Journal of Virology, vol. 77, no. 4, pp. 2779–2783, 2003. View at Publisher · View at Google Scholar · View at Scopus
  64. J. Hu and R. Renne, “Characterization of the minimal replicator of Kaposi's sarcoma-associated herpesvirus latent origin,” Journal of Virology, vol. 79, no. 4, pp. 2637–2642, 2005. View at Publisher · View at Google Scholar · View at Scopus
  65. A. J. Barbera, M. E. Ballestas, and K. M. Kaye, “The Kaposi's sarcoma-associated herpesvirus latency-associated nuclear antigen 1 N terminus is essential for chromosome association, DNA replication, and episome persistence,” Journal of Virology, vol. 78, no. 1, pp. 294–301, 2004. View at Publisher · View at Google Scholar · View at Scopus
  66. M. Canham and S. J. Talbot, “A naturally occurring C-terminal truncated isoform of the latent nuclear antigen of Kaposi's sarcoma-associated herpesvirus does not associate with viral episomal DNA,” Journal of General Virology, vol. 85, no. 6, pp. 1363–1369, 2004. View at Publisher · View at Google Scholar · View at Scopus
  67. T. Komatsu, M. E. Ballestas, A. J. Barbera, B. Kelley-Clarke, and K. M. Kaye, “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, vol. 319, no. 2, pp. 225–236, 2004. View at Publisher · View at Google Scholar · View at Scopus
  68. E. Ohsaki, K. Ueda, S. Sakakibara, E. Do, K. Yada, and K. Yamanishi, “Poly(ADP-ribose) polymerase 1 binds to Kaposi's sarcoma-associated herpesvirus (KSHV) terminal repeat sequence and modulates KSHV replication in latency,” Journal of Virology, vol. 78, no. 18, pp. 9936–9946, 2004. View at Publisher · View at Google Scholar · View at Scopus
  69. S. C. Verma, B. G. Bajaj, Q. Cai, H. Si, T. Seelhammer, and E. S. Robertson, “Latency-associated nuclear antigen of Kaposi's sarcoma-associated herpesvirus recruits uracil DNA glycosylase 2 at the terminal repeats and is important for latent persistence of the virus,” Journal of Virology, vol. 80, no. 22, pp. 11178–11190, 2006. View at Publisher · View at Google Scholar · View at Scopus
  70. S. C. Verma, T. Choudhuri, R. Kaul, and E. S. Robertson, “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,” Journal of Virology, vol. 80, no. 5, pp. 2243–2256, 2006. View at Publisher · View at Google Scholar · View at Scopus
  71. S. C. Verma, T. Choudhuri, and E. S. Robertson, “The minimal replicator element of the Kaposi's sarcoma-associated herpesvirus terminal repeat supports replication in a semiconservative and cell-cycle-dependent manner,” Journal of Virology, vol. 81, no. 7, pp. 3402–3413, 2007. View at Publisher · View at Google Scholar · View at Scopus
  72. W. Stedman, Z. Deng, F. Lu, and P. M. Lieberman, “ORC, MCM, and histone hyperacetylation at the Kaposi's sarcoma-associated herpesvirus latent replication origin,” Journal of Virology, vol. 78, no. 22, pp. 12566–12575, 2004. View at Publisher · View at Google Scholar · View at Scopus
  73. C. Lim, C. Choi, and J. Choe, “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,” Journal of Virology, vol. 78, no. 13, pp. 7248–7256, 2004. View at Publisher · View at Google Scholar · View at Scopus
  74. B. Kelley-Clarke, E. De Leon-Vazquez, K. Slain, A. J. Barbera, and K. M. Kaye, “Role of Kaposi's sarcoma-associated herpesvirus C-terminal LANA chromosome binding in episome persistence,” Journal of Virology, vol. 83, no. 9, pp. 4326–4337, 2009. View at Publisher · View at Google Scholar · View at Scopus
  75. B. Kelley-Clarke, M. E. Ballestas, V. Srinivasan et al., “Determination of Kaposi's sarcoma-associated herpesvirus C-terminal latency-associated nuclear antigen residues mediating chromosome association and DNA binding,” Journal of Virology, vol. 81, no. 8, pp. 4348–4356, 2007. View at Publisher · View at Google Scholar · View at Scopus
  76. B. Kelley-Clarke, M. E. Ballestas, T. Komatsu, and K. M. Kaye, “Kaposi's sarcoma herpesvirus C-terminal LANA concentrates at pericentromeric and peri-telomeric regions of a subset of mitotic chromosomes,” Virology, vol. 357, no. 2, pp. 149–157, 2007. View at Publisher · View at Google Scholar · View at Scopus
  77. H. Shinohara, M. Fukushi, M. Higuchi et al., “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,” Journal of Virology, vol. 76, no. 24, pp. 12917–12924, 2002. View at Publisher · View at Google Scholar · View at Scopus
  78. A. Krithivas, M. Fujimuro, M. Weidner, D. B. Young, and S. D. Hayward, “Protein interactions targeting the latency-associated nuclear antigen of Kaposi's sarcoma-associated herpesvirus to cell chromosomes,” Journal of Virology, vol. 76, no. 22, pp. 11596–11604, 2002. View at Publisher · View at Google Scholar · View at Scopus
  79. S. Matsumura, L. M. Persson, L. Wong, and A. C. Wilson, “The latency-associated nuclear antigen interacts with MeCP2 and nucleosomes through separate domains,” Journal of Virology, vol. 84, no. 5, pp. 2318–2330, 2010. View at Publisher · View at Google Scholar · View at Scopus
  80. J. You, V. Srinivasan, G. V. Denis et al., “Kaposi's sarcoma-associated herpesvirus latency-associated nuclear antigen interacts with bromodomain protein Brd4 on host mitotic chromosomes,” Journal of Virology, vol. 80, no. 18, pp. 8909–8919, 2006. View at Publisher · View at Google Scholar · View at Scopus
  81. B. Xiao, S. C. Verma, Q. Cai et al., “Bub1 and CENP-F can contribute to Kaposi's sarcoma-associated herpesvirus genome persistence by targeting LANA to kinetochores,” Journal of Virology, vol. 84, no. 19, pp. 9718–9732, 2010. View at Publisher · View at Google Scholar
  82. F. C. Ye, F. U. C. Zhou, M. Y. Seung, J. P. Xie, P. J. Browning, and S. J. Gao, “Disruption of Kaposi's sarcoma-associated herpesvirus latent nuclear antigen leads to abortive episome persistence,” Journal of Virology, vol. 78, no. 20, pp. 11121–11129, 2004. View at Publisher · View at Google Scholar · View at Scopus
  83. A. Krithivas, D. B. Young, G. Liao, D. Greene, and S. D. Hayward, “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,” Journal of Virology, vol. 74, no. 20, pp. 9637–9645, 2000. View at Publisher · View at Google Scholar · View at Scopus
  84. H. Y. Pan, Y. J. Zhang, X. P. Wang, J. H. Deng, F. U. C. Zhou, and S. J. Gao, “Identification of a novel cellular transcriptional repressor interacting with the latent nuclear antigen of Kaposi's sarcoma-associated herpesvirus,” Journal of Virology, vol. 77, no. 18, pp. 9758–9768, 2003. View at Publisher · View at Google Scholar · View at Scopus
  85. K. Mattsson, C. Kiss, G. M. Platt et al., “Latent nuclear antigen of Kaposi's sarcoma herpesvirus/human herpesvirus-8 induces and relocates RING3 to nuclear heterochromatin regions,” Journal of General Virology, vol. 83, no. 1, pp. 179–188, 2002. View at Scopus
  86. G. M. Platt, G. R. Simpson, S. Mittnacht, and T. F. Schulz, “Latent nuclear antigen of Kaposi's sarcoma-associated herpesvirus interacts with RING3, a homolog of the Drosophila female sterile homeotic (fsh) gene,” Journal of Virology, vol. 73, no. 12, pp. 9789–9795, 1999. View at Scopus
  87. M. Shamay, A. Krithivas, J. Zhang, and S. D. Hayward, “Recruitment of the de novo DNA methyltransferase Dnmt3a by Kaposi's sarcoma-associated herpesvirus LANA,” Proceedings of the National Academy of Sciences of the United States of America, vol. 103, no. 39, pp. 14554–14559, 2006. View at Publisher · View at Google Scholar · View at Scopus
  88. K. E. Lan, D. A. Kuppers, S. C. Verma, N. Sharma, M. Murakami, and E. S. Robertson, “Induction of Kaposi's sarcoma-associated herpesvirus latency-associated nuclear antigen by the lytic transactivator RTA: a novel mechanism for establishment of latency,” Journal of Virology, vol. 79, no. 12, pp. 7453–7465, 2005. View at Publisher · View at Google Scholar · View at Scopus
  89. K. E. Lan, D. A. Kuppers, S. C. Verma, and E. S. Robertson, “Kaposi's sarcoma-associated herpesvirus-encoded latency-associated nuclear antigen inhibits lytic replication by targeting Rta: a potential mechanism for virus-mediated control of latency,” Journal of Virology, vol. 78, no. 12, pp. 6585–6594, 2004. View at Publisher · View at Google Scholar · View at Scopus
  90. K. E. Lan, D. A. Kuppers, and E. S. Robertson, “Kaposi's sarcoma-associated herpesvirus reactivation is regulated by interaction of latency-associated nuclear antigen with recombination signal sequence-binding protein Jκ, the major downstream effector of the notch signaling pathway,” Journal of Virology, vol. 79, no. 6, pp. 3468–3478, 2005. View at Publisher · View at Google Scholar · View at Scopus
  91. Q. Li, F. Zhou, F. Ye, and S. J. Gao, “Genetic disruption of KSHV major latent nuclear antigen LANA enhances viral lytic transcriptional program,” Virology, vol. 379, no. 2, pp. 234–244, 2008. View at Publisher · View at Google Scholar · View at Scopus
  92. Q. I. L. Cai, J. S. Knight, S. C. Verma, P. Zald, and E. S. Robertson, “EC5S ubiquitin complex is recruited by KSHV latent antigen LANA for degradation of the VHL and p53 tumor suppressors,” PLoS Pathogens, vol. 2, no. 10, p. e116, 2006. View at Publisher · View at Google Scholar · View at Scopus
  93. J. Friborg Jr., W. P. Kong, M. O. Hottlger, and G. J. Nabel, “p53 Inhibition by the LANA protein of KSHV protects against cell death,” Nature, vol. 402, no. 6764, pp. 889–894, 1999. View at Publisher · View at Google Scholar · View at Scopus
  94. H. Katano, Y. Sato, and T. Sata, “Expression of p53 and human herpesvirus-8 (HHV-8)-encoded latency-associated nuclear antigen with inhibition of apoptosis in HHV-8-associated malignancies,” Cancer, vol. 92, no. 12, pp. 3076–3084, 2001. View at Publisher · View at Google Scholar · View at Scopus
  95. S. A. Radkov, P. Kellam, and C. Boshoff, “The latent nuclear antigen of Kaposi sarcoma-associated herpesvirus targets the retinoblastoma-E2F pathway and with the oncogene Hras transforms primary rat cells,” Nature Medicine, vol. 6, no. 10, pp. 1121–1127, 2000. View at Publisher · View at Google Scholar · View at Scopus
  96. M. Fujimuro, F. Y. Wu, C. Aprhys et al., “A novel viral mechanism for dysregulation of β-catenin in Kaposi's sarcoma-associated herpesvirus latency,” Nature Medicine, vol. 9, no. 3, pp. 300–306, 2003. View at Publisher · View at Google Scholar · View at Scopus
  97. T. Hagen, “Characterization of the interaction between latency-associated nuclear antigen and glycogen synthase kinase 3β,” Journal of Virology, vol. 83, no. 12, pp. 6312–6317, 2009. View at Publisher · View at Google Scholar · View at Scopus
  98. J. Liu, H. J. Martin, G. Liao, and S. D. Hayward, “The Kaposi's sarcoma-associated herpesvirus LANA protein stabilizes and activates c-Myc,” Journal of Virology, vol. 81, no. 19, pp. 10451–10459, 2007. View at Publisher · View at Google Scholar · View at Scopus
  99. X. Li, S. Chen, J. Feng, H. Deng, and R. Sun, “Myc is required for the maintenance of Kaposi's sarcoma-associated herpesvirus latency,” Journal of Virology, vol. 84, no. 17, pp. 8945–8948, 2010. View at Publisher · View at Google Scholar
  100. D. Godden-Kent, S. J. Talbot, C. Boshoff et al., “The cyclin encoded by Kaposi's sarcoma-associated herpesvirus stimulates cdk6 to phosphorylate the retinoblastoma protein and histone H1,” Journal of Virology, vol. 71, no. 6, pp. 4193–4198, 1997. View at Scopus
  101. M. Ellis, Y. P. Chew, L. Fallis et al., “Degradation of p27(Kip) cdk inhibitor triggered by Kaposi's sarcoma virus cyclin-cdk6 complex,” The EMBO Journal, vol. 18, no. 3, pp. 644–653, 1999. View at Publisher · View at Google Scholar · View at Scopus
  102. D. J. Mann, E. S. Child, C. Swanton, H. Laman, and N. Jones, “Modulation of p27(Kip1) levels by the cyclin encoded by Kaposi's sarcoma-associated herpesvirus,” The EMBO Journal, vol. 18, no. 3, pp. 654–663, 1999. View at Publisher · View at Google Scholar · View at Scopus
  103. P. M. Ojala, K. Yamamoto, E. Castanos-Velez, et al., “The apoptotic v-cyclin-CDK6 complex phosphorylates and inactivates Bcl-2,” Nature Cell Biology, vol. 2, no. 11, pp. 819–825, 2000.
  104. G. Sarek, A. Järviluoma, and P. M. Ojala, “KSHV viral cyclin inactivates p27KIP1 through Ser10 and Thr187 phosphorylation in proliferating primary effusion lymphomas,” Blood, vol. 107, no. 2, pp. 725–732, 2006. View at Publisher · View at Google Scholar
  105. G. Sarek, A. Järviluoma, H. M. Moore et al., “Nucleophosmin phosphorylation by v-cyclin-CDK6 controls KSHV latency,” PLoS Pathogens, vol. 6, no. 3, Article ID e1000818, 2010. View at Publisher · View at Google Scholar · View at Scopus
  106. A. T. Hoge, S. B. Hendrickson, and W. H. Burns, “Murine gammaherpesvirus 68 cyclin D homologue is required for efficient reactivation from latency,” Journal of Virology, vol. 74, no. 15, pp. 7016–7023, 2000. View at Publisher · View at Google Scholar · View at Scopus
  107. M. Thome, P. Schneider, K. Hofmann et al., “Viral FLICE-inhibitory proteins (FLIPs) prevent apoptosis induced by death receptors,” Nature, vol. 386, no. 6624, pp. 517–521, 1997. View at Publisher · View at Google Scholar · View at Scopus
  108. P. M. Chaudhary, A. Jasmin, M. T. Eby, and L. Hood, “Modulation of the NF-κB pathway by virally encoded death effector domains-containing proteins,” Oncogene, vol. 18, no. 42, pp. 5738–5746, 1999. View at Publisher · View at Google Scholar · View at Scopus
  109. N. Field, W. Low, M. Daniels et al., “KSHV vFLIP binds to IKK-γ to activate IKK,” Journal of Cell Science, vol. 116, no. 18, pp. 3721–3728, 2003. View at Publisher · View at Google Scholar · View at Scopus
  110. H. Matta and P. M. Chaudhary, “Activation of alternative NF-κB pathway by human herpes virus 8-encoded Fas-associated death domain-like IL-1β-converting enzyme inhibitory protein (vFLIP),” Proceedings of the National Academy of Sciences of the United States of America, vol. 101, no. 25, pp. 9399–9404, 2004. View at Publisher · View at Google Scholar
  111. H. Matta, L. Mazzacurati, S. Schamus, et al., “Kaposi's sarcoma-associated herpesvirus (KSHV) oncoprotein K13 bypasses TRAFs and directly interacts with the IkappaB kinase complex to selectively activate NF-kappaB without JNK activation,” The Journal of Biological Chemistry, vol. 282, no. 34, pp. 24858–24865, 2007.
  112. H. J. Brown, M. J. Song, H. Deng, T. T. Wu, G. Cheng, and R. Sun, “NF-κB inhibits gammaherpesvirus lytic replication,” Journal of Virology, vol. 77, no. 15, pp. 8532–8540, 2003. View at Publisher · View at Google Scholar · View at Scopus
  113. M. Sgarbanti, M. Arguello, B. R. TenOever, A. Battistini, R. Lin, and J. Hiscott, “A requirement for NF-κB induction in the production of replication-competent HHV-8 virions,” Oncogene, vol. 23, no. 34, pp. 5770–5780, 2004. View at Publisher · View at Google Scholar · View at Scopus
  114. J. Zhao, V. Punj, H. Matta et al., “K13 blocks KSHV lytic replication and deregulates vIL6 nad hIL6 expression: a model of lytic replication induced clonal selection in viral oncogenesis,” PLoS ONE, vol. 2, no. 10, Article ID e1067, 2007. View at Publisher · View at Google Scholar
  115. C. Grossmann and D. Ganem, “Effects of NFκB activation on KSHV latency and lytic reactivation are complex and context-dependent,” Virology, vol. 375, no. 1, pp. 94–102, 2008. View at Publisher · View at Google Scholar · View at Scopus
  116. F. C. Ye, F. U. C. Zhou, J. P. Xie et al., “Kaposi's sarcoma-associated herpesvirus latent gene vFLIP inhibits viral lytic replication through NF-κB-mediated suppression of the AP-1 pathway: a novel mechanism of virus control of latency,” Journal of Virology, vol. 82, no. 9, pp. 4235–4249, 2008. View at Publisher · View at Google Scholar · View at Scopus
  117. S. Pfeffer, A. Sewer, M. Lagos-Quintana et al., “Identification of microRNAs of the herpesvirus family,” Nature Methods, vol. 2, no. 4, pp. 269–276, 2005. View at Publisher · View at Google Scholar · View at Scopus
  118. X. Cai, S. Lu, Z. Zhang, C. M. Gonzalez, B. Damania, and B. R. Cullen, “Kaposi's sarcoma-associated herpesvirus expresses an array of viral microRNAs in latently infected cells,” Proceedings of the National Academy of Sciences of the United States of America, vol. 102, no. 15, pp. 5570–5575, 2005. View at Publisher · View at Google Scholar · View at Scopus
  119. M. A. Samols, J. Hu, R. L. Skalsky, and R. Renne, “Cloning and identification of a MicroRNA cluster within the latency-associated region of Kaposi's sarcoma-associated herpesvirus,” Journal of Virology, vol. 79, no. 14, pp. 9301–9305, 2005. View at Publisher · View at Google Scholar · View at Scopus
  120. X. Lei, Z. Bai, F. Ye et al., “Regulation of NF-B inhibitor IBα and viral replication by a KSHV microRNA,” Nature Cell Biology, vol. 12, no. 2, pp. 193–199, 2010. View at Publisher · View at Google Scholar · View at Scopus
  121. C.-C. Lu, Z. Li, C.-Y. Chu et al., “MicroRNAs encoded by Kaposi's sarcoma-associated herpesvirus regulate viral life cycle,” EMBO Reports, vol. 11, no. 10, pp. 784–790, 2010. View at Publisher · View at Google Scholar
  122. P. Bellare and D. Ganem, “Regulation of KSHV lytic switch protein expression by a virus-encoded microRNA: an evolutionary adaptation that fine-tunes lytic Reactivation,” Cell Host and Microbe, vol. 6, no. 6, pp. 570–575, 2010. View at Publisher · View at Google Scholar · View at Scopus
  123. J. M. Ziegelbauer, C. S. Sullivan, and D. Ganem, “Tandem array-based expression screens identify host mRNA targets of virus-encoded microRNAs,” Nature Genetics, vol. 41, no. 1, pp. 130–134, 2009. View at Publisher · View at Google Scholar · View at Scopus
  124. F. Lu, W. Stedman, M. Yousef, R. Renne, and P. M. Lieberman, “Epigenetic regulation of Kaposi's sarcoma-associated herpesvirus latency by virus-encoded microRNAs that target Rta and the cellular Rbl2-DNMT pathway,” Journal of Virology, vol. 84, no. 6, pp. 2697–2706, 2010. View at Publisher · View at Google Scholar · View at Scopus
  125. E. Gottwein, N. Mukherjee, C. Sachse et al., “A viral microRNA functions as an orthologue of cellular miR-155,” Nature, vol. 450, no. 7172, pp. 1096–1099, 2007. View at Publisher · View at Google Scholar · View at Scopus
  126. R. L. Skalsky, M. A. Samols, K. B. Plaisance et al., “Kaposi's sarcoma-associated herpesvirus encodes an ortholog of miR-155,” Journal of Virology, vol. 81, no. 23, pp. 12836–12845, 2007. View at Publisher · View at Google Scholar · View at Scopus
  127. Z. Qin, E. Freitas, R. Sullivan et al., “Upregulation of xCT by KSHV-encoded microRNAs facilitates KSHV dissemination and persistence in an environment of oxidative stress,” PLoS Pathogens, vol. 6, no. 1, Article ID e1000742, 2010. View at Publisher · View at Google Scholar · View at Scopus
  128. J. R. Abend, T. Uldrick, and J. M. Ziegelbauer, “Regulation of tumor necrosis factor-like weak inducer of apoptosis receptor protein (TWEAKR) expression by Kaposi's sarcoma-associated herpesvirus microrna prevents tweak-induced apoptosis and inflammatory cytokine expression,” Journal of Virology, vol. 84, no. 23, pp. 12139–12151, 2010. View at Publisher · View at Google Scholar
  129. Y. He, B. Vogelstein, V. E. Velculescu, N. Papadopoulos, and K. W. Kinzler, “The antisense transcriptomes of human cells,” Science, vol. 322, no. 5909, pp. 1855–1857, 2008. View at Publisher · View at Google Scholar · View at Scopus
  130. S. Chandriani, Y. Xu, and D. Ganem, “The lytic transcriptome of Kaposi's sarcoma-associated herpesvirus reveals extensive transcription of noncoding regions, including regions antisense to important genes,” Journal of Virology, vol. 84, no. 16, pp. 7934–7942, 2010. View at Publisher · View at Google Scholar
  131. Y.-T. Lin, R. P. Kincaid, D. Arasappan, S. E. Dowd, S. P. Hunicke-Smith, and C. S. Sullivan, “Small RNA profiling reveals antisense transcription throughout the KSHV genome and novel small RNAs,” RNA, vol. 16, no. 8, pp. 1540–1558, 2010. View at Publisher · View at Google Scholar
  132. Y. Xu and D. Ganem, “Making sense of antisense: seemingly noncoding RNAs antisense to the master regulator of Kaposi's sarcoma-associated herpesvirus lytic replication do not regulate that transcript but serve as mRNAs encoding small peptides,” Journal of Virology, vol. 84, no. 11, pp. 5465–5475, 2010. View at Publisher · View at Google Scholar · View at Scopus
  133. B. Ensoli, C. Sgadari, G. Barillari, M. C. Sirianni, M. Stürzl, and P. Monini, “Biology of Kaposi's sarcoma,” European Journal of Cancer, vol. 37, no. 10, pp. 1251–1269, 2001. View at Publisher · View at Google Scholar · View at Scopus
  134. D. A. Davis, A. S. Rinderknecht, J. Paul Zoeteweij et al., “Hypoxia induces lytic replication of Kaposi sarcoma-associated herpesvirus,” Blood, vol. 97, no. 10, pp. 3244–3250, 2001. View at Publisher · View at Google Scholar · View at Scopus
  135. M. Haque, D. A. Davis, V. Wang, I. Widmer, and R. Yarchoan, “Kaposi's sarcoma-associated herpesvirus (human herpesvirus 8) contains hypoxia response elements: relevance to lytic induction by hypoxia,” Journal of Virology, vol. 77, no. 12, pp. 6761–6768, 2003. View at Publisher · View at Google Scholar · View at Scopus
  136. M. Haque, V. Wang, D. A. Davis, Z. M. Zheng, and R. Yarchoan, “Genetic organization and hypoxic activation of the Kaposi's sarcoma-associated herpesvirus ORF34-37 gene cluster,” Journal of Virology, vol. 80, no. 14, pp. 7037–7051, 2006. View at Publisher · View at Google Scholar · View at Scopus
  137. L. Dalton-Griffin, S. J. Wilson, and P. Kellam, “X-box binding protein 1 contributes to induction of the Kaposi's sarcoma-associated herpesvirus lytic cycle under hypoxic conditions,” Journal of Virology, vol. 83, no. 14, pp. 7202–7209, 2009. View at Publisher · View at Google Scholar · View at Scopus
  138. Q. Cai, K. Lan, S. C. Verma, H. Si, D. Lin, and E. S. Robertson, “Kaposi's sarcoma-associated herpesvirus latent protein LANA interacts with HIF-1α to upregulate RTA expression during hypoxia: latency control under low oxygen conditions,” Journal of Virology, vol. 80, no. 16, pp. 7965–7975, 2006. View at Publisher · View at Google Scholar
  139. R. Merat, A. Amara, C. Lebbe, H. De The, P. Morel, and A. Saib, “HIV-1 infection of primary effusion lymphoma cell line triggers Kaposi's sarcoma-associated herpesvirus (KSHV) reactivation,” International Journal of Cancer, vol. 97, no. 6, pp. 791–795, 2002. View at Publisher · View at Google Scholar · View at Scopus
  140. V. Varthakavi, R. M. Smith, H. Deng, R. Sun, and P. Spearman, “Human immunodeficiency virus type-1 activates lytic cycle replication of Kaposi's sarcoma-associated herpesvirus through induction of KSHV Rta,” Virology, vol. 297, no. 2, pp. 270–280, 2002. View at Publisher · View at Google Scholar
  141. Y. I. Zeng, X. Zhang, Z. Huang et al., “Intracellular Tat of human immunodeficiency virus type 1 activates lytic cycle replication of Kaposi's sarcoma-associated herpesvirus: role of JAK/STAT signaling,” Journal of Virology, vol. 81, no. 5, pp. 2401–2417, 2007. View at Publisher · View at Google Scholar · View at Scopus
  142. J. Vieira, P. O'Hearn, L. Kimball, B. Chandran, and L. Corey, “Activation of Kaposi's sarcoma-associated herpesvirus (human herpesvirus 8) lytic replication by human cytomegalovirus,” Journal of Virology, vol. 75, no. 3, pp. 1378–1386, 2001. View at Publisher · View at Google Scholar · View at Scopus
  143. C. Lu, Y. I. Zeng, Z. Huang et al., “Human herpesvirus 6 activates lytic cycle replication of Kaposi's sarcoma-associated herpesvirus,” American Journal of Pathology, vol. 166, no. 1, pp. 173–183, 2005. View at Scopus
  144. DI. Qin, Y. I. Zeng, C. Qian et al., “Induction of lytic cycle replication of Kaposi's sarcoma-associated herpesvirus by herpes simplex virus type 1: involvement of IL-10 and IL-4,” Cellular Microbiology, vol. 10, no. 3, pp. 713–728, 2008. View at Publisher · View at Google Scholar · View at Scopus
  145. S. M. Gregory, J. A. West, P. J. Dillon, C. Hilscher, D. P. Dittmer, and B. Damania, “Toll-like receptor signaling controls reactivation of KSHV from latency,” Proceedings of the National Academy of Sciences of the United States of America, vol. 106, no. 28, pp. 11725–11730, 2009. View at Publisher · View at Google Scholar · View at Scopus
  146. M. Mercader, B. Taddeo, J. R. Panella, B. Chandran, B. J. Nickoloff, and K. E. Foreman, “Induction of HHV-8 lytic cycle replication by inflammatory cytokines produced by HIV-1-infected T cells,” American Journal of Pathology, vol. 156, no. 6, pp. 1961–1971, 2000. View at Scopus
  147. D. J. Blackbourn, S. Fujimura, T. Kutzkey, and J. A. Levy, “Induction of human herpesvirus-8 gene expression by recombinant interferon gamma,” AIDS, vol. 14, no. 1, pp. 98–99, 2000. View at Publisher · View at Google Scholar · View at Scopus
  148. S. Milligan, M. Robinson, E. O'Donnell, and D. J. Blackbourn, “Inflammatory cytokines inhibit Kaposi's sarcoma-associated herpesvirus lytic gene transcription in in vitro-infected endothelial cells,” Journal of Virology, vol. 78, no. 5, pp. 2591–2596, 2004. View at Publisher · View at Google Scholar · View at Scopus
  149. F. C. Ye, F. C. Zhou, and R. G. Bedolla, “Reactive oxygen species hydrogen peroxide mediates Kaposi’s sarcoma-associated herpesvirus reactivation from latency,” PLoS Pathogens, vol. 7, no. 5, Article ID e1002054, 2011.
  150. X. Li, J. Feng, and R. Sun, “Oxidative stress induces reactivation of Kaposi's sarcoma-associated herpesvirus and death of primary effusion lymphoma cells,” Journal of Virology, vol. 85, no. 2, pp. 715–724, 2011.
  151. L. Gil, G. Martínez, I. González et al., “Contribution to characterization of oxidative stress in HIV/AIDS patients,” Pharmacological Research, vol. 47, no. 3, pp. 217–224, 2003. View at Publisher · View at Google Scholar · View at Scopus
  152. M. Khatami, “Inflammation, aging, and cancer: tumoricidal versus tumorigenesis of immunity,” Cell Biochemistry and Biophysics, vol. 55, no. 2, pp. 55–79, 2009. View at Publisher · View at Google Scholar
  153. V. E. Laubach and I. L. Kron, “Pulmonary inflammation after lung transplantation,” Surgery, vol. 146, no. 1, pp. 1–4, 2009. View at Publisher · View at Google Scholar · View at Scopus
  154. A. A. Salahudeen and R. K. Bruick, “Maintaining mammalian iron and oxygen homeostasis: sensors, regulation, and cross-talk,” Annals of the New York Academy of Sciences, vol. 1177, pp. 30–38, 2009. View at Publisher · View at Google Scholar · View at Scopus
  155. T. Simonart, J. C. Noel, G. Andrei et al., “Iron as a potential co-factor in the pathogenesis of Kaposi's sarcoma?” International Journal of Cancer, vol. 78, no. 6, pp. 720–726, 1998. View at Publisher · View at Google Scholar · View at Scopus
  156. A. S. Johnson, N. Maronian, and J. Vieira, “Activation of Kaposi's sarcoma-associated herpesvirus lytic gene expression during epithelial differentiation,” Journal of Virology, vol. 79, no. 21, pp. 13769–13777, 2005. View at Publisher · View at Google Scholar · View at Scopus
  157. F. Yu, J. Feng, J. N. Harada, S. K. Chanda, S. C. Kenney, and R. Sun, “B cell terminal differentiation factor XBP-1 induces reactivation of Kaposi's sarcoma-associated herpesvirus,” The FEBS Letters, vol. 581, no. 18, pp. 3485–3488, 2007. View at Publisher · View at Google Scholar · View at Scopus
  158. S. J. Wilson, E. H. Tsao, B. L. J. Webb et al., “X box binding protein XBP-1s transactivates the Kaposi's Sarcoma-Associated Herpesvirus (KSHV) ORF50 promoter, linking plasma cell differentiation to KSHV reactivation from latency,” Journal of Virology, vol. 81, no. 24, pp. 13578–13586, 2007. View at Publisher · View at Google Scholar · View at Scopus
  159. T. Simonart, “Iron: a target for the management of Kaposi's sarcoma?” BMC Cancer, vol. 4, article 1, 2004. View at Publisher · View at Google Scholar · View at Scopus
  160. T. Simonart, “Role of environmental factors in the pathogenesis of classic and African-endemic Kaposi sarcoma,” Cancer Letters, vol. 244, no. 1, pp. 1–7, 2006. View at Publisher · View at Google Scholar · View at Scopus
  161. H. J. Cho, F. Yu, R. Sun, D. Lee, and M. J. Song, “Lytic induction of Kaposi's sarcoma-associated herpesvirus in primary effusion lymphoma cells with natural products identified by a cell-based fluorescence moderate-throughput screening,” Archives of Virology, vol. 153, no. 8, pp. 1517–1525, 2008. View at Publisher · View at Google Scholar · View at Scopus
  162. D. Whitby, V. A. Marshall, R. K. Bagni et al., “Reactivation of Kaposi's sarcoma-associated herpesvirus by natural products from Kaposi's sarcoma endemic regions,” International Journal of Cancer, vol. 120, no. 2, pp. 321–328, 2007. View at Publisher · View at Google Scholar · View at Scopus
  163. J. P. Zoeteweij, A. V. Moses, A. S. Rinderknecht et al., “Targeted inhibition of calcineurin signaling blocks calcium-dependent reactivation of Kaposi sarcoma-associated herpesvirus,” Blood, vol. 97, no. 8, pp. 2374–2380, 2001. View at Publisher · View at Google Scholar · View at Scopus
  164. E. Deutsch, A. Cohen, G. Kazimirsky et al., “Role of protein kinase C δ in reactivation of Kaposi's sarcoma-associated herpesvirus,” Journal of Virology, vol. 78, no. 18, pp. 10187–10192, 2004. View at Publisher · View at Google Scholar · View at Scopus
  165. F. Yu, J. N. Harada, H. J. Brown et al., “Systematic identification of cellular signals reactivating Kaposi sarcoma-associated herpesvirus,” PLoS Pathogens, vol. 3, no. 3, p. e44, 2007. View at Publisher · View at Google Scholar · View at Scopus
  166. S. E. Wang, F. Y. Wu, H. Chen, M. Shamay, Q. Zheng, and G. S. Hayward, “Early activation of the Kaposi's sarcoma-associated herpesvirus RTA, RAP, and MTA promoters by the tetradecanoyl phorbol acetate-induced AP1 pathway,” Journal of Virology, vol. 78, no. 8, pp. 4248–4267, 2004. View at Publisher · View at Google Scholar · View at Scopus
  167. D. P. AuCoin, K. S. Colletti, S. A. Cei, I. Papousková, M. Tarrant, and G. S. Pari, “Amplification of the Kaposi's sarcoma-associated herpesvirus/human herpesvirus 8 lytic origin of DNA replication is dependent upon a cis-acting AT-rich region and an ORF50 response element and the trans-acting factors ORF50 (K-Rta) and K8 (K-bZIP),” Virology, vol. 318, no. 2, pp. 542–555, 2004. View at Publisher · View at Google Scholar · View at Scopus
  168. J. Xie, A. O. Ajibade, F. Ye, K. Kuhne, and S. J. Gao, “Reactivation of Kaposi's sarcoma-associated herpesvirus from latency requires MEK/ERK, JNK and p38 multiple mitogen-activated protein kinase pathways,” Virology, vol. 371, no. 1, pp. 139–154, 2008. View at Publisher · View at Google Scholar · View at Scopus
  169. H. Pan, J. Xie, F. Ye, and S. J. Gao, “Modulation of Kaposi's sarcoma-associated herpesvirus infection and replication by MEK/ERK, JNK, and p38 multiple mitogen-activated protein kinase pathways during primary infection,” Journal of Virology, vol. 80, no. 11, pp. 5371–5382, 2006. View at Publisher · View at Google Scholar · View at Scopus
  170. J. Xie, H. Pan, S. Yoo, and S. J. Gao, “Kaposi's sarcoma-associated herpesvirus induction of AP-1 and interleukin 6 during primary infection mediated by multiple mitogen-activated protein kinase pathways,” Journal of Virology, vol. 79, no. 24, pp. 15027–15037, 2005. View at Publisher · View at Google Scholar · View at Scopus
  171. A. Cohen, C. Brodie, and R. Sarid, “An essential role of ERK signalling in TPA-induced reactivation of Kaposi's sarcoma-associated herpesvirus,” Journal of General Virology, vol. 87, no. 4, pp. 795–802, 2006. View at Publisher · View at Google Scholar · View at Scopus
  172. P. W. Ford, B. A. Bryan, O. F. Dyson, D. A. Weidner, V. Chintalgattu, and S. M. Akula, “Raf/MEK/ERK signalling triggers reactivation of Kaposi's sarcoma-associated herpesvirus latency,” Journal of General Virology, vol. 87, no. 5, pp. 1139–1144, 2006. View at Publisher · View at Google Scholar · View at Scopus
  173. F. Cheng, M. Weidner-Glunde, M. Varjosalo et al., “KSHV reactivation from latency requires pim-1 and pim-3 kinases to inactivate the latency-associated nuclear antigen LANA,” PLoS Pathogens, vol. 5, no. 3, Article ID e1000324, 2009. View at Publisher · View at Google Scholar · View at Scopus
  174. Y. Izumiya, C. Izumiya, D. Hsia, T. J. Ellison, P. A. Luciw, and H. J. Kung, “NF-κB serves as a cellular sensor of Kaposi's sarcoma-associated herpesvirus latency and negatively regulates K-Rta by antagonizing the RBP-Jκ coactivator,” Journal of Virology, vol. 83, no. 9, pp. 4435–4446, 2009. View at Publisher · View at Google Scholar · View at Scopus
  175. M. Lagunoff, J. Bechtel, E. Venetsanakos et al., “De novo infection and serial transmission of Kaposi's sarcoma-associated herpesvirus in cultured endothelial cells,” Journal of Virology, vol. 76, no. 5, pp. 2440–2448, 2002. View at Publisher · View at Google Scholar · View at Scopus
  176. H. H. Krishnan, P. P. Naranatt, M. S. Smith, L. Zeng, C. Bloomer, and B. Chandran, “Concurrent expression of latent and a limited number of lytic genes with immune modulation and antiapoptotic function by Kaposi's sarcoma-associated herpesvirus early during infection of primary endothelial and fibroblast cells and subsequent decline of lytic gene expression,” Journal of Virology, vol. 78, no. 7, pp. 3601–3620, 2004. View at Publisher · View at Google Scholar · View at Scopus
  177. C. Foglieni, S. Scabini, D. Belloni et al., “Productive infection of HUVEC by HHV-8 is associated with changes compatible with angiogenic transformations,” European Journal of Histochemistry, vol. 49, no. 3, pp. 273–284, 2005. View at Scopus
  178. M. Y. Seung, F. U. C. Zhou, F. C. Ye, H. Y. Pan, and S. J. Gao, “Early and sustained expression of latent and host modulating genes in coordinated transcriptional program of KSHV productive primary infection of human primary endothelial cells,” Virology, vol. 343, no. 1, pp. 47–64, 2005. View at Publisher · View at Google Scholar · View at Scopus
  179. N. Sharma-Walia, H. H. Krishnan, P. P. Naranatt, L. Zeng, M. S. Smith, and B. Chandran, “ERK1/2 and MEK1/2 induced by Kaposi's sarcoma-associated herpesvirus (human herpesvirus 8) early during infection of target cells are essential for expression of viral genes and for establishment of infection,” Journal of Virology, vol. 79, no. 16, pp. 10308–10329, 2005. View at Publisher · View at Google Scholar · View at Scopus
  180. L. I. Peng, T. T. Wu, J. H. Tchieu et al., “Inhibition of the phosphatidylinositol 3-kinase-Akt pathway enhances gamma-2 herpesvirus lytic replication and facilitates reactivation from latency,” Journal of General Virology, vol. 91, no. 2, pp. 463–469, 2010. View at Publisher · View at Google Scholar · View at Scopus
  181. J. Chen, K. Ueda, S. Sakakibara et al., “Activation of latent Kaposi's sarcoma-associated herpesvirus by demethylation of the promoter of the lytic transactivator,” Proceedings of the National Academy of Sciences of the United States of America, vol. 98, no. 7, pp. 4119–4124, 2001. View at Publisher · View at Google Scholar · View at Scopus
  182. F. Lu, J. Zhou, A. Wiedmer, K. Madden, Y. Yuan, and P. M. Lieberman, “Chromatin remodeling of the Kaposi's sarcoma-associated herpesvirus ORF50 promoter correlates with reactivation from latency,” Journal of Virology, vol. 77, no. 21, pp. 11425–11435, 2003. View at Publisher · View at Google Scholar · View at Scopus
  183. Q. H. Li and S. J. Gao, “Reactivation of KSHV from latency by class III histone deacetylase inhibitors,” in Proceedings of the 13th International Workshop on Kaposi's Sarcoma-Associated Herpesvirus and Related Agents, Los Angeles, Calif, USA, August 2010.
  184. D. M. Lukac, R. Renne, J. R. Kirshner, and D. Ganem, “Reactivation of Kaposi's sarcoma-associated herpesvirus infection from latency by expression of the ORF 50 transactivator, a homolog of the EBV R protein,” Virology, vol. 252, no. 2, pp. 304–312, 1998. View at Publisher · View at Google Scholar · View at Scopus
  185. R. Sun, S. U. F. Lin, L. Gradoville, Y. Yuan, F. Zhu, and G. Miller, “A viral gene that activates lytic cycle expression of Kaposi's sarcoma-associated herpesvirus,” Proceedings of the National Academy of Sciences of the United States of America, vol. 95, no. 18, pp. 10866–10871, 1998. View at Scopus
  186. L. Gradoville, J. Gerlach, E. Grogan et al., “Kaposi's sarcoma-associated herpesvirus open reading frame 50/Rta protein activates the entire viral lytic cycle in the HH-B2 primary effusion lymphoma cell line,” Journal of Virology, vol. 74, no. 13, pp. 6207–6212, 2000. View at Publisher · View at Google Scholar · View at Scopus
  187. Y. Xu, D. P. AuCoin, A. Rodriguez Huete, S. A. Cei, L. J. Hanson, and G. S. Pari, “A kaposi's sarcoma-associated herpesvirus/human herpesvirus 8 ORF50 deletion mutant is defective for reactivation of latent virus and DNA replication,” Journal of Virology, vol. 79, no. 6, pp. 3479–3487, 2005. View at Publisher · View at Google Scholar · View at Scopus
  188. H. Deng, A. Young, and R. Sun, “Auto-activation of the rta gene of human herpesvirus-8/Kaposi's sarcoma-associated herpesvirus,” Journal of General Virology, vol. 81, no. 12, pp. 3043–3048, 2000. View at Scopus
  189. W. Bu, D. Palmeri, R. Krishnan et al., “Identification of direct transcriptional targets of the Kaposi's sarcoma-associated herpesvirus Rta lytic switch protein by conditional nuclear localization,” Journal of Virology, vol. 82, no. 21, pp. 10709–10723, 2008. View at Publisher · View at Google Scholar · View at Scopus
  190. H. Deng, M. J. Song, J. T. Chu, and R. Sun, “Transcriptional regulation of the interleukin-6 gene of human herpesvirus 8 (Kaposi's sarcoma-associated herpesvirus),” Journal of Virology, vol. 76, no. 16, pp. 8252–8264, 2002. View at Publisher · View at Google Scholar · View at Scopus
  191. . Moon Jung Song, H. J. Brown, T. T. Wu, and R. Sun, “Transcription activation of polyadenylated nuclear RNA by Rta in human herpesvirus 8/Kaposi's sarcoma-associated herpesvirus,” Journal of Virology, vol. 75, no. 7, pp. 3129–3140, 2001. View at Publisher · View at Google Scholar · View at Scopus
  192. H. Byun, Y. Gwack, S. Hwang, and J. Choe, “Kaposi's sarcoma-associated herpesvirus open reading frame (ORF) 50 transactivates K8 and ORF57 promoters via heterogeneous response elements,” Molecules and Cells, vol. 14, no. 2, pp. 185–191, 2002. View at Scopus
  193. D. M. Lukac, L. Garibyan, J. R. Kirshner, D. Palmeri, and D. Ganem, “DNA binding by Kaposi's sarcoma-associated herpesvirus lytic switch protein is necessary for transcriptional activation of two viral delayed early promoters,” Journal of Virology, vol. 75, no. 15, pp. 6786–6799, 2001. View at Publisher · View at Google Scholar · View at Scopus
  194. K. Ueda, K. Ishikawa, K. Nishimura, et al., “Kaposi's sarcoma-associated herpesvirus (human herpesvirus 8) replication and transcription factor activates the K9 (vIRF) gene through two distinct cis elements by a non-DNA-binding mechanism,” Journal of Virology, vol. 76, no. 23, pp. 12044–12054, 2002.
  195. B. S. Bowser, S. Morris, M. J. Song, R. Sun, and B. Damania, “Characterization of Kaposi's sarcoma-associated herpesvirus (KSHV) K1 promoter activation by Rta,” Virology, vol. 348, no. 2, pp. 309–327, 2006. View at Publisher · View at Google Scholar · View at Scopus
  196. M. J. Song, H. Deng, and R. Sun, “Comparative study of regulation of RTA-responsive genes in Kaposi's sarcoma-associated herpesvirus/human herpesvirus 8,” Journal of Virology, vol. 77, no. 17, pp. 9451–9462, 2003. View at Publisher · View at Google Scholar · View at Scopus
  197. W. T. Seaman and E. B. Quinlivan, “Lytic switch protein (ORF50) response element in the Kaposi's sarcoma-associated herpesvirus K8 promoter is located within but does not require a palindromic structure,” Virology, vol. 310, no. 1, pp. 72–84, 2003. View at Publisher · View at Google Scholar · View at Scopus
  198. J. Ziegelbauer, A. Grundhoff, and D. Ganem, “Exploring the DNA binding interactions of the Kaposi's sarcoma-associated herpesvirus lytic switch protein by selective amplification of bound sequences in vitro,” Journal of Virology, vol. 80, no. 6, pp. 2958–2967, 2006. View at Publisher · View at Google Scholar · View at Scopus
  199. J. Chen, F. Ye, J. Xie, K. Kuhne, and S. J. Gao, “Genome-wide identification of binding sites for Kaposi's sarcoma-associated herpesvirus lytic switch protein, RTA,” Virology, vol. 386, no. 2, pp. 290–302, 2009. View at Publisher · View at Google Scholar · View at Scopus
  200. L. Zhang, J. Chiu, and J.-C. Lin, “Activation of human herpesvirus 8 (HHV-8) thymidine kinase (TK) TATAA- less promoter by HHV-80RF50 gene product is SP1 dependent,” DNA and Cell Biology, vol. 17, no. 9, pp. 735–742, 1998.
  201. J. Ye, D. Shedd, and G. Miller, “An Sp1 response element in the Kaposi's sarcoma-associated herpesvirus open reading frame 50 promoter mediates lytic cycle induction by butyrate,” Journal of Virology, vol. 79, no. 3, pp. 1397–1408, 2005. View at Publisher · View at Google Scholar · View at Scopus
  202. K. D. Carroll, F. Khadim, S. Spadavecchia, D. Palmeri, and D. M. Lukac, “Direct interactions of Kaposi's sarcoma-associated herpesvirus/human herpesvirus 8 ORF50/Rta protein with the cellular protein octamer-1 and DNA are critical for specifying transactivation of a delayed-early promoter and stimulating viral reactivation,” Journal of Virology, vol. 81, no. 16, pp. 8451–8467, 2007. View at Publisher · View at Google Scholar · View at Scopus
  203. P. J. Chang and G. Miller, “Autoregulation of DNA binding and protein stability of Kaposi's sarcoma-associated herpesvirus ORF50 protein,” Journal of Virology, vol. 78, no. 19, pp. 10657–10673, 2004. View at Publisher · View at Google Scholar · View at Scopus
  204. S. Sakakibara, K. Ueda, J. Chen, T. Okuno, and K. Yamanishi, “Octamer-binding sequence is a key element for the autoregulation of Kaposi's sarcoma-associated herpesvirus ORF50/Lyta gene expression,” Journal of Virology, vol. 75, no. 15, pp. 6894–6900, 2001. View at Publisher · View at Google Scholar · View at Scopus
  205. K. D. Carroll, W. Bu, D. Palmeri et al., “Kaposi's sarcoma-associated herpesvirus lytic switch protein stimulates DNA binding of RBP-Jk/CSL to activate the Notch pathway,” Journal of Virology, vol. 80, no. 19, pp. 9697–9709, 2006. View at Publisher · View at Google Scholar · View at Scopus
  206. P. J. Chang, J. Boonsiri, S. S. Wang, L. I. Y. Chen, and G. Miller, “Binding of RBP-Jκ (CSL) protein to the promoter of the Kaposi's sarcoma-associated herpesvirus ORF47 (gL) gene is a critical but not sufficient determinant of transactivation by ORF50 protein,” Virology, vol. 398, no. 1, pp. 38–48, 2010. View at Publisher · View at Google Scholar · View at Scopus
  207. L. M. Persson and A. C. Wilson, “Wide-scale use of notch signaling factor CSL/RBP-Jκ in RTA-mediated activation of kaposi's sarcoma-associated herpesvirus lytic genes,” Journal of Virology, vol. 84, no. 3, pp. 1334–1347, 2010. View at Publisher · View at Google Scholar · View at Scopus
  208. K. E. Lan, M. Murakami, T. Choudhuri, D. A. Kuppers, and E. S. Robertson, “Intracellular-activated Notch1 can reactivate Kaposi's sarcoma-associated herpesvirus from latency,” Virology, vol. 351, no. 2, pp. 393–403, 2006. View at Publisher · View at Google Scholar · View at Scopus
  209. H. Chang, D. P. Dittmer, S. Y. Chul, Y. Hong, and J. U. Jung, “Role of notch signal transduction in Kaposi's sarcoma-associated herpesvirus gene expression,” Journal of Virology, vol. 79, no. 22, pp. 14371–14382, 2005. View at Publisher · View at Google Scholar · View at Scopus
  210. Y. Gwack, H. J. Baek, H. Nakamura et al., “Principal role of TRAP/Mediator and SWI/SNF complexes in Kaposi's sarcoma-associated herpesvirus RTA-mediated lytic reactivation,” Molecular and Cellular Biology, vol. 23, no. 6, pp. 2055–2067, 2003. View at Publisher · View at Google Scholar · View at Scopus
  211. S. Wang, S. Liu, M. H. Wu, Y. Geng, and C. Wood, “Identification of a cellular protein that interacts and synergizes with the RTA (ORF50) protein of Kaposi's sarcoma-associated herpesvirus in transcriptional activation,” Journal of Virology, vol. 75, no. 24, pp. 11961–11973, 2001. View at Publisher · View at Google Scholar · View at Scopus
  212. Z. Yang and C. Wood, “The transcriptional repressor K-RBP modulates RTA-mediated transactivation and lytic replication of Kaposi's sarcoma-associated herpesvirus,” Journal of Virology, vol. 81, no. 12, pp. 6294–6306, 2007. View at Publisher · View at Google Scholar · View at Scopus
  213. Z. Yang, H. J. Wen, V. Minhas, and C. Wood, “The zinc finger DNA-binding domain of K-RBP plays an important role in regulating Kaposi's sarcoma-associated herpesvirus RTA-mediated gene expression,” Virology, vol. 391, no. 2, pp. 221–231, 2009. View at Publisher · View at Google Scholar · View at Scopus
  214. P. C. Chang, L. D. Fitzgerald, A. Van Geelen et al., “Kruppel-associated box domain-associated protein-1 as a latency regulator for Kaposi's sarcoma-associated herpesvirus and its modulation by the viral protein kinase,” Cancer Research, vol. 69, no. 14, pp. 5681–5689, 2009. View at Publisher · View at Google Scholar · View at Scopus
  215. S. E. Wang, F. Y. Wu, M. Fujimuro, J. Zong, S. Diane Hayward, and G. S. Hayward, “Role of CCAAT/enhancer-binding protein alpha (C/EBPα) in activation of the Kaposi's sarcoma-associated herpesvirus (KSHV) lytic-cycle replication-associated protein (RAP) promoter in cooperation with the KSHV replication and transcription activator (RTA) and RAP,” Journal of Virology, vol. 77, no. 1, pp. 600–623, 2003. View at Publisher · View at Google Scholar · View at Scopus
  216. S. E. Wang, F. Y. Wu, Y. Yu, and G. S. Hayward, “CCAAT/enhancer-binding protein-α is induced during the early stages of Kaposi's sarcoma-associated herpesvirus (KSHV) lytic cycle reactivation and together with the KSHV replication and transcription activator (RTA) cooperatively stimulates the viral RTA, MTA, and PAN promoters,” Journal of Virology, vol. 77, no. 17, pp. 9590–9612, 2003. View at Publisher · View at Google Scholar · View at Scopus
  217. Y. Wang and Y. Yuan, “Essential role of RBP-Jκ in activation of the K8 delayed-early promoter of Kaposi's sarcoma-associated herpesvirus by ORF50/RTA,” Virology, vol. 359, no. 1, pp. 19–27, 2007. View at Publisher · View at Google Scholar · View at Scopus
  218. Z. Yang, Z. Yan, and C. Wood, “Kaposi's sarcoma-associated herpesvirus transactivator RTA promotes degradation of the repressors to regulate viral lytic replication,” Journal of Virology, vol. 82, no. 7, pp. 3590–3603, 2008. View at Publisher · View at Google Scholar · View at Scopus
  219. Y. Yu, S. E. Wang, and G. S. Hayward, “The KSHV immediate-early transcription factor RTA encodes ubiquitin E3 ligase activity that targets IRF7 for proteosome-mediated degradation,” Immunity, vol. 22, no. 1, pp. 59–70, 2005. View at Publisher · View at Google Scholar · View at Scopus
  220. F. Gould, S. M. Harrison, E. W. Hewitt, and A. Whitehouse, “Kaposi's sarcoma-associated herpesvirus RTA promotes degradation of the Hey1 repressor protein through the ubiquitin proteasome pathway,” Journal of Virology, vol. 83, no. 13, pp. 6727–6738, 2009. View at Publisher · View at Google Scholar · View at Scopus
  221. Y. Wang, Q. Tang, G. G. Maul, and Y. Yuan, “Kaposi's sarcoma-associated herpesvirus ori-Lyt-dependent DNA replication: dual role of replication and transcription activator,” Journal of Virology, vol. 80, no. 24, pp. 12171–12186, 2006. View at Publisher · View at Google Scholar · View at Scopus
  222. Y. Wang, H. Li, M. Y. Chan, F. X. Zhu, D. M. Lukac, and Y. Yuan, “Kaposi's sarcoma-associated herpesvirus ori-Lyt-dependent DNA replication: cis-acting requirements for replication and ori-Lyt-associated RNA transcription,” Journal of Virology, vol. 78, no. 16, pp. 8615–8629, 2004. View at Publisher · View at Google Scholar · View at Scopus
  223. D. P. AuCoin, K. S. Colletti, Y. Xu, S. A. Cei, and G. S. Pari, “Kaposi's sarcoma-associated herpesvirus (human herpesvirus 8) contains two functional lytic origins of DNA replication,” Journal of Virology, vol. 76, no. 15, pp. 7890–7896, 2002. View at Publisher · View at Google Scholar · View at Scopus
  224. Z. Han and S. Swaminathan, “Kaposi's sarcoma-associated herpesvirus lytic gene ORF57 is essential for infectious virion production,” Journal of Virology, vol. 80, no. 11, pp. 5251–5260, 2006. View at Publisher · View at Google Scholar · View at Scopus
  225. V. Majerciak, N. Pripuzova, J. P. McCoy, S. J. Gao, and Z. M. Zheng, “Targeted disruption of Kaposi's sarcoma-associated herpesvirus ORF57 in the viral genome is detrimental for the expression of ORF59, K8α, and K8.1 and the production of infectious virus,” Journal of Virology, vol. 81, no. 3, pp. 1062–1071, 2007. View at Publisher · View at Google Scholar · View at Scopus
  226. D. Palmeri, S. Spadavecchia, K. D. Carroll, and D. M. Lukac, “Promoter- and cell-specific transcriptional transactivation by the Kaposi's sarcoma-associated herpesvirus ORF57/Mta protein,” Journal of Virology, vol. 81, no. 24, pp. 13299–13314, 2007. View at Publisher · View at Google Scholar · View at Scopus
  227. P. Malik, D. J. Blackbourn, M. F. Cheng, G. S. Hayward, and J. B. Clements, “Functional co-operation between the Kaposi's sarcoma-associated herpesvirus ORF57 and ORF50 regulatory proteins,” Journal of General Virology, vol. 85, no. 8, pp. 2155–2166, 2004. View at Publisher · View at Google Scholar · View at Scopus
  228. M. Nekorchuk, Z. Han, T. T. Hsieh, and S. Swaminathan, “Kaposi's sarcoma-associated herpesvirus ORF57 protein enhances mRNA accumulation independently of effects on nuclear RNA export,” Journal of Virology, vol. 81, no. 18, pp. 9990–9998, 2007. View at Publisher · View at Google Scholar · View at Scopus
  229. J. R. Boyne, B. R. Jackson, A. Taylor, S. A. MacNab, and A. Whitehouse, “Kaposi's sarcoma-associated herpesvirus ORF57 protein interacts with PYM to enhance translation of viral intronless mRNAs,” The EMBO Journal, vol. 29, no. 11, pp. 1851–1864, 2010. View at Publisher · View at Google Scholar · View at Scopus
  230. V. Majerciak, K. Yamanegi, E. Allemand, M. Kruhlak, A. R. Krainer, and Z. M. Zheng, “Kaposi's sarcoma-associated herpesvirus ORF57 functions as a viral splicing factor and promotes expression of intron-containing viral lytic genes in spliceosome-mediated RNA splicing,” Journal of Virology, vol. 82, no. 6, pp. 2792–2801, 2008. View at Publisher · View at Google Scholar · View at Scopus
  231. J. R. Boyne and A. Whitehouse, “Nucleolar disruption impairs Kaposi's sarcoma-associated herpesvirus ORF57-mediated nuclear export of intronless viral mRNAs,” The FEBS Letters, vol. 583, no. 22, pp. 3549–3556, 2009. View at Publisher · View at Google Scholar · View at Scopus
  232. P. Malik, D. J. Blackbourn, and J. B. Clements, “The evolutionarily conserved Kaposi's sarcoma-associated herpesvirus ORF57 protein interacts with REF protein and acts as an RNA export factor,” The Journal of Biological Chemistry, vol. 279, no. 31, pp. 33001–33011, 2004. View at Publisher · View at Google Scholar · View at Scopus
  233. B. B. Sahin, D. Patel, and N. K. Conrad, “Kaposi's sarcoma-associated herpesvirus ORF57 protein binds and protects a nuclear noncoding rna from cellular RNA decay pathways,” PLoS Pathogens, vol. 6, no. 3, Article ID e1000799, 2010. View at Publisher · View at Google Scholar · View at Scopus
  234. Y. Izumiya, S. U. F. Lin, T. Ellison et al., “Kaposi's sarcoma-associated herpesvirus K-bZIP is a coregulator of K-Rta: physical association and promoter-dependent transcriptional repression,” Journal of Virology, vol. 77, no. 2, pp. 1441–1451, 2003. View at Publisher · View at Google Scholar · View at Scopus
  235. Y. Izumiya, T. J. Ellison, E. T. H. Yeh, J. U. Jung, P. A. Luciw, and H. J. Kung, “Kaposi's sarcoma-associated herpesvirus K-bZIP represses gene transcription via SUMO modification,” Journal of Virology, vol. 79, no. 15, pp. 9912–9925, 2005. View at Publisher · View at Google Scholar · View at Scopus
  236. T. J. Ellison, Y. Izumiya, C. Izumiya, P. A. Luciw, and H. J. Kung, “A comprehensive analysis of recruitment and transactivation potential of K-Rta and K-bZIP during reactivation of Kaposi's sarcoma-associated herpesvirus,” Virology, vol. 387, no. 1, pp. 76–88, 2009. View at Publisher · View at Google Scholar · View at Scopus
  237. Y. Izumiya, C. Izumiya, A. Van Geelen et al., “Kaposi's sarcoma-associated herpesvirus-encoded protein kinase and its interaction with K-bZIP,” Journal of Virology, vol. 81, no. 3, pp. 1072–1082, 2007. View at Publisher · View at Google Scholar · View at Scopus
  238. A. G. Polson, L. Huang, D. M. Lukac et al., “Kaposi's sarcoma-associated herpesvirus K-bZIP protein is phosphorylated by cyclin-dependent kinases,” Journal of Virology, vol. 75, no. 7, pp. 3175–3184, 2001. View at Publisher · View at Google Scholar · View at Scopus
  239. C. Rossetto, I. Yamboliev, and G. S. Pari, “Kaposi's sarcoma-associated herpesvirus/human herpesvirus 8 K-bZIP modulates latency-associated nuclear protein-mediated suppression of lytic origin-dependent DNA synthesis,” Journal of Virology, vol. 83, no. 17, pp. 8492–8501, 2009. View at Publisher · View at Google Scholar · View at Scopus
  240. C. Rossetto, Y. Gao, I. Yamboliev, I. Papousková, and G. Pari, “Transcriptional repression of K-Rta by Kaposi's sarcoma-associated herpesvirus K-bZIP is not required for oriLyt-dependent DNA replication,” Virology, vol. 369, no. 2, pp. 340–350, 2007. View at Publisher · View at Google Scholar · View at Scopus
  241. S. Lefort and L. Flamand, “Kaposi's sarcoma-associated herpesvirus K-bZIP protein is necessary for lytic viral gene expression, DNA replication, and virion production in primary effusion lymphoma cell lines,” Journal of Virology, vol. 83, no. 11, pp. 5869–5880, 2009. View at Publisher · View at Google Scholar · View at Scopus