Tegument protein control of latent herpesvirus establishment and animation

Pellet P, Roizman B: Herpesviridae: A Brief Introduction. Fields Virology. Edited by: Howley P. 2007, Philadelphia: Lippincott, 2480-2499. 5 Bresnahan WA, Shenk TE: UL82 virion protein activates expression of immediate early viral genes in human cytomegalovirus-infected cells. Proc Natl Acad Sci USA. 2000, 97: 14506-14511. 10.1073/pnas.97.26.14506. Moriuchi H, Moriuchi M, Straus SE, Cohen JI: Varicella-zoster virus open reading frame 10 protein, the herpes simplex virus VP16 homolog, transactivates herpesvirus immediate-early gene promoters. J Virol. 1993, 67: 2739-2746. Wysocka J, Herr W: The herpes simplex virus VP16-induced complex: the makings of a regulatory switch. Trends Biochem Sci. 2003, 28: 294-304. 10.1016/S0968-0004(03)00088-4. Nicholson IP, Sutherland JS, Chaudry TN, Blewett EL, Barry PA, Nicholl MJ, Preston CM: Properties of virion transactivator proteins encoded by primate cytomegaloviruses. Virol J. 2009, 6: 65-10.1186/1743-422X-6-65. Schreiber A, Harter G, Schubert A, Bunjes D, Mertens T, Michel D: Antiviral treatment of cytomegalovirus infection and resistant strains. Expert Opin Pharmacother. 2009, 10: 191-209. 10.1517/14656560802678138. Billaud G, Thouvenot D, Morfin F: Drug targets in herpes simplex and Epstein Barr Virus infections. Infect Disord Drug Targets. 2009, 9: 117-125. Roizman B, Knipe D, Whitley R: Herpes Simplex Viruses. Fields Virology. Edited by: Howley P. 2007, Philadelphia: Lippincott, 2501-2601. 5 Cohen J, Straus S, Arvin A: Varicella-Zoster Virus Replication, Pathogenesis, and Management. Fields Virology. Edited by: Howley P. 2007, Philadelphia: Lippincott, 2773-2818. 5 Sinclair J: Human cytomegalovirus: Latency and reactivation in the myeloid lineage. J Clin Virol. 2008, 41: 180-185. 10.1016/j.jcv.2007.11.014. Mendelson M, Monard S, Sissons P, Sinclair J: Detection of endogenous human cytomegalovirus in CD34+ bone marrow progenitors. J Gen Virol. 1996, 77 (Pt 12): 3099-3102. 10.1099/0022-1317-77-12-3099. Mocarski E, Shenk T, Pass R: Cytomegaloviruses. Fields Virology. Edited by: Howley P. 2007, Philadelphia: Lippincott, 2701-2772. 5 De Bolle L, Naesens L, De Clercq E: Update on human herpesvirus 6 biology, clinical features, and therapy. Clin Microbiol Rev. 2005, 18: 217-245. 10.1128/CMR.18.1.217-245.2005. Yamanishi K, Mori Y, Pellet P: Human Herpesviruses 6 and 7. Fields Virology. Edited by: Howley P. 2007, Philadelphia: Lippincott, 2820-2845. 5 Miyake F, Yoshikawa T, Sun H, Kakimi A, Ohashi M, Akimoto S, Nishiyama Y, Asano Y: Latent infection of human herpesvirus 7 in CD4(+) T lymphocytes. J Med Virol. 2006, 78: 112-116. 10.1002/jmv.20511. Coleman CB, Nealy MS, Tibbetts SA: Immature and transitional B cells are latency reservoirs for a gammaherpesvirus. J Virol. 2010, 84: 13045-13052. 10.1128/JVI.01455-10. Rickinson A, Kieff E: Epstein-Barr Virus. Fields Virology. Edited by: Howley P. 2007, Philadelphia: Lippincott, 2655-2700. 5 Ganem D: Kaposi's Sarcoma-associated Herpesvirus. Fields Virology. Edited by: Howley P. 2007, Philadelphia: Lippincott, 2848-2888. 5 Efstathiou S, Preston CM: Towards an understanding of the molecular basis of herpes simplex virus latency. Virus Res. 2005, 111: 108-119. 10.1016/j.virusres.2005.04.017. Bloom DC, Giordani NV, Kwiatkowski DL: Epigenetic regulation of latent HSV-1 gene expression. Biochim Biophys Acta. 2010, 1799: 246-256. Knipe DM, Cliffe A: Chromatin control of herpes simplex virus lytic and latent infection. Nat Rev Microbiol. 2008, 6: 211-221. 10.1038/nrmicro1794. Kutluay SB, Triezenberg SJ: Role of chromatin during herpesvirus infections. Biochim Biophys Acta. 2009, 1790: 456-466. Perng GC, Jones C: Towards an understanding of the herpes simplex virus type 1 latency-reactivation cycle. Interdiscip Perspect Infect Dis. 2010, 2010: 262415- Sissons JG, Bain M, Wills MR: Latency and reactivation of human cytomegalovirus. J Infect. 2002, 44: 73-77. 10.1053/jinf.2001.0948. Bego MG, St Jeor S: Human cytomegalovirus infection of cells of hematopoietic origin: HCMV-induced immunosuppression, immune evasion, and latency. Exp Hematol. 2006, 34: 555-570. 10.1016/j.exphem.2005.11.012. Slobedman B, Cao JZ, Avdic S, Webster B, McAllery S, Cheung AK, Tan JC, Abendroth A: Human cytomegalovirus latent infection and associated viral gene expression. Future Microbiol. 2010, 5: 883-900. 10.2217/fmb.10.58. Sinclair J: Chromatin structure regulates human cytomegalovirus gene expression during latency, reactivation and lytic infection. Biochim Biophys Acta. 2010, 1799: 286-295. Sinclair J, Sissons P: Latency and reactivation of human cytomegalovirus. J Gen Virol. 2006, 87: 1763-1779. 10.1099/vir.0.81891-0. Amon W, Farrell PJ: Reactivation of Epstein-Barr virus from latency. Rev Med Virol. 2005, 15: 149-156. 10.1002/rmv.456. Young LS, Rickinson AB: Epstein-Barr virus: 40 years on. Nat Rev Cancer. 2004, 4: 757-768. 10.1038/nrc1452. Tsurumi T, Fujita M, Kudoh A: Latent and lytic Epstein-Barr virus replication strategies. Rev Med Virol. 2005, 15: 3-15. 10.1002/rmv.441. Young LS, Dawson CW, Eliopoulos AG: The expression and function of Epstein-Barr virus encoded latent genes. Mol Pathol. 2000, 53: 238-247. 10.1136/mp.53.5.238. Tempera I, Lieberman PM: Chromatin organization of gammaherpesvirus latent genomes. Biochim Biophys Acta. 2010, 1799: 236-245. Camarena V, Kobayashi M, Kim JY, Roehm P, Perez R, Gardner J, Wilson AC, Mohr I, Chao MV: Nature and duration of growth factor signaling through receptor tyrosine kinases regulates HSV-1 latency in neurons. Cell Host Microbe. 2010, 8: 320-330. 10.1016/j.chom.2010.09.007. Danaher RJ, Jacob RJ, Miller CS: Establishment of a quiescent herpes simplex virus type 1 infection in neurally-differentiated PC12 cells. J Neurovirol. 1999, 5: 258-267. 10.3109/13550289909015812. Jamieson DR, Robinson LH, Daksis JI, Nicholl MJ, Preston CM: Quiescent viral genomes in human fibroblasts after infection with herpes simplex virus type 1 Vmw65 mutants. J Gen Virol. 1995, 76 (Pt 6): 1417-1431. 10.1099/0022-1317-76-6-1417. Russell J, Preston CM: An in vitro latency system for herpes simplex virus type 2. J Gen Virol. 1986, 67 (Pt 2): 397-403. 10.1099/0022-1317-67-2-397. Wilcox CL, Johnson EM: Nerve growth factor deprivation results in the reactivation of latent herpes simplex virus in vitro. J Virol. 1987, 61: 2311-2315. Ma SD, Hegde S, Young KH, Sullivan R, Rajesh D, Zhou Y, Jankowska-Gan E, Burlingham WJ, Sun X, Gulley ML, et al: A new model of EBV infection reveals an important role for early lytic viral protein expression in the development of lymphomas. J Virol. 2010, 85: 165-177. 10.1128/JVI.01512-10. Smith MS, Goldman DC, Bailey AS, Pfaffle DL, Kreklywich CN, Spencer DB, Othieno FA, Streblow DN, Garcia JV, Fleming WH, Nelson JA: Granulocyte-colony stimulating factor reactivates human cytomegalovirus in a latently infected humanized mouse model. Cell Host Microbe. 2010, 8: 284-291. 10.1016/j.chom.2010.08.001. Ace CI, McKee TA, Ryan JM, Cameron JM, Preston CM: Construction and characterization of a herpes simplex virus type 1 mutant unable to transinduce immediate-early gene expression. J Virol. 1989, 63: 2260-2269. Imai Y, Apakupakul K, Krause PR, Halford WP, Margolis TP: Investigation of the mechanism by which herpes simplex virus type 1 LAT sequences modulate preferential establishment of latent infection in mouse trigeminal ganglia. J Virol. 2009, 83: 7873-7882. 10.1128/JVI.00043-09. Margolis TP, Imai Y, Yang L, Vallas V, Krause PR: Herpes simplex virus type 2 (HSV-2) establishes latent infection in a different population of ganglionic neurons than HSV-1: role of latency-associated transcripts. J Virol. 2007, 81: 1872-1878. 10.1128/JVI.02110-06. Proenca JT, Coleman HM, Connor V, Winton DJ, Efstathiou S: A historical analysis of herpes simplex virus promoter activation in vivo reveals distinct populations of latently infected neurones. J Gen Virol. 2008, 89: 2965-2974. 10.1099/vir.0.2008/005066-0. Margolis TP, Dawson CR, LaVail JH: Herpes simplex viral infection of the mouse trigeminal ganglion. Immunohistochemical analysis of cell populations. Invest Ophthalmol Vis Sci. 1992, 33: 259-267. Yang L, Voytek CC, Margolis TP: Immunohistochemical analysis of primary sensory neurons latently infected with herpes simplex virus type 1. J Virol. 2000, 74: 209-217. 10.1128/JVI.74.1.209-217.2000. Sawtell NM, Thompson RL: Herpes simplex virus type 1 latency-associated transcription unit promotes anatomical site-dependent establishment and reactivation from latency. J Virol. 1992, 66: 2157-2169. Speck PG, Simmons A: Synchronous appearance of antigen-positive and latently infected neurons in spinal ganglia of mice infected with a virulent strain of herpes simplex virus. J Gen Virol. 1992, 73 (Pt 5): 1281-1285. 10.1099/0022-1317-73-5-1281. Lachmann RH, Sadarangani M, Atkinson HR, Efstathiou S: An analysis of herpes simplex virus gene expression during latency establishment and reactivation. J Gen Virol. 1999, 80 (Pt 5): 1271-1282. Sawtell NM: Comprehensive quantification of herpes simplex virus latency at the single-cell level. J Virol. 1997, 71: 5423-5431. Thompson RL, Sawtell NM: Replication of herpes simplex virus type 1 within trigeminal ganglia is required for high frequency but not high viral genome copy number latency. J Virol. 2000, 74: 965-974. 10.1128/JVI.74.2.965-974.2000. Coen DM, Kosz-Vnenchak M, Jacobson JG, Leib DA, Bogard CL, Schaffer PA, Tyler KL, Knipe DM: Thymidine kinase-negative herpes simplex virus mutants establish latency in mouse trigeminal ganglia but do not reactivate. Proc Natl Acad Sci USA. 1989, 86: 4736-4740. 10.1073/pnas.86.12.4736. Speck PG, Simmons A: Divergent molecular pathways of productive and latent infection with a virulent strain of herpes simplex virus type 1. J Virol. 1991, 65: 4001-4005. Katan M, Haigh A, Verrijzer CP, van der Vliet PC, O'Hare P: Characterization of a cellular factor which interacts functionally with Oct-1 in the assembly of a multicomponent transcription complex. Nucleic Acids Res. 1990, 18: 6871-6880. 10.1093/nar/18.23.6871. Wilson AC, LaMarco K, Peterson MG, Herr W: The VP16 accessory protein HCF is a family of polypeptides processed from a large precursor protein. Cell. 1993, 74: 115-125. 10.1016/0092-8674(93)90299-6. Xiao P, Capone JP: A cellular factor binds to the herpes simplex virus type 1 transactivator Vmw65 and is required for Vmw65-dependent protein-DNA complex assembly with Oct-1. Mol Cell Biol. 1990, 10: 4974-4977. Stern S, Tanaka M, Herr W: The Oct-1 homoeodomain directs formation of a multiprotein-DNA complex with the HSV transactivator VP16. Nature. 1989, 341: 624-630. 10.1038/341624a0. O'Hare P, Goding CR, Haigh A: Direct combinatorial interaction between a herpes simplex virus regulatory protein and a cellular octamer-binding factor mediates specific induction of virus immediate-early gene expression. Embo J. 1988, 7: 4231-4238. O'Hare P, Goding CR: Herpes simplex virus regulatory elements and the immunoglobulin octamer domain bind a common factor and are both targets for virion transactivation. Cell. 1988, 52: 435-445. La Boissiere S, Hughes T, O'Hare P: HCF-dependent nuclear import of VP16. Embo J. 1999, 18: 480-489. 10.1093/emboj/18.2.480. Preston CM, Frame MC, Campbell ME: A complex formed between cell components and an HSV structural polypeptide binds to a viral immediate early gene regulatory DNA sequence. Cell. 1988, 52: 425-434. 10.1016/S0092-8674(88)80035-7. Herrera FJ, Triezenberg SJ: VP16-dependent association of chromatin-modifying coactivators and underrepresentation of histones at immediate-early gene promoters during herpes simplex virus infection. J Virol. 2004, 78: 9689-9696. 10.1128/JVI.78.18.9689-9696.2004. Triezenberg SJ, Kingsbury RC, McKnight SL: Functional dissection of VP16, the trans-activator of herpes simplex virus immediate early gene expression. Genes Dev. 1988, 2: 718-729. 10.1101/gad.2.6.718. Goodrich JA, Hoey T, Thut CJ, Admon A, Tjian R: Drosophila TAFII40 interacts with both a VP16 activation domain and the basal transcription factor TFIIB. Cell. 1993, 75: 519-530. 10.1016/0092-8674(93)90386-5. Ingles CJ, Shales M, Cress WD, Triezenberg SJ, Greenblatt J: Reduced binding of TFIID to transcriptionally compromised mutants of VP16. Nature. 1991, 351: 588-590. 10.1038/351588a0. Klemm RD, Goodrich JA, Zhou S, Tjian R: Molecular cloning and expression of the 32-kDa subunit of human TFIID reveals interactions with VP16 and TFIIB that mediate transcriptional activation. Proc Natl Acad Sci USA. 1995, 92: 5788-5792. 10.1073/pnas.92.13.5788. Lin YS, Ha I, Maldonado E, Reinberg D, Green MR: Binding of general transcription factor TFIIB to an acidic activating region. Nature. 1991, 353: 569-571. 10.1038/353569a0. Uesugi M, Nyanguile O, Lu H, Levine AJ, Verdine GL: Induced alpha helix in the VP16 activation domain upon binding to a human TAF. Science. 1997, 277: 1310-1313. 10.1126/science.277.5330.1310. Tal-Singer R, Pichyangkura R, Chung E, Lasner TM, Randazzo BP, Trojanowski JQ, Fraser NW, Triezenberg SJ: The transcriptional activation domain of VP16 is required for efficient infection and establishment of latency by HSV-1 in the murine peripheral and central nervous systems. Virology. 1999, 259: 20-33. 10.1006/viro.1999.9756. Hancock MH, Cliffe AR, Knipe DM, Smiley JR: Herpes simplex virus VP16, but not ICP0, is required to reduce histone occupancy and enhance histone acetylation on viral genomes in U2OS osteosarcoma cells. J Virol. 2010, 84: 1366-1375. 10.1128/JVI.01727-09. Peng H, Nogueira ML, Vogel JL, Kristie TM: Transcriptional coactivator HCF-1 couples the histone chaperone Asf1b to HSV-1 DNA replication components. Proc Natl Acad Sci USA. 2010, 107: 2461-2466. 10.1073/pnas.0911128107. Oh J, Fraser NW: Temporal association of the herpes simplex virus genome with histone proteins during a lytic infection. J Virol. 2008, 82: 3530-3537. 10.1128/JVI.00586-07. Leinbach SS, Summers WC: The structure of herpes simplex virus type 1 DNA as probed by micrococcal nuclease digestion. J Gen Virol. 1980, 51: 45-59. 10.1099/0022-1317-51-1-45. Placek BJ, Berger SL: Chromatin dynamics during herpes simplex virus-1 lytic infection. Biochim Biophys Acta. 2010, 1799: 223-227. Paulus C, Nitzsche A, Nevels M: Chromatinisation of herpesvirus genomes. Rev Med Virol. 2010, 20: 34-50. 10.1002/rmv.632. Kent JR, Zeng PY, Atanasiu D, Gardner J, Fraser NW, Berger SL: During lytic infection herpes simplex virus type 1 is associated with histones bearing modifications that correlate with active transcription. J Virol. 2004, 78: 10178-10186. 10.1128/JVI.78.18.10178-10186.2004. Huang J, Kent JR, Placek B, Whelan KA, Hollow CM, Zeng PY, Fraser NW, Berger SL: Trimethylation of histone H3 lysine 4 by Set1 in the lytic infection of human herpes simplex virus 1. J Virol. 2006, 80: 5740-5746. 10.1128/JVI.00169-06. Memedula S, Belmont AS: Sequential recruitment of HAT and SWI/SNF components to condensed chromatin by VP16. Curr Biol. 2003, 13: 241-246. 10.1016/S0960-9822(03)00048-4. Neely KE, Hassan AH, Wallberg AE, Steger DJ, Cairns BR, Wright AP, Workman JL: Activation domain-mediated targeting of the SWI/SNF complex to promoters stimulates transcription from nucleosome arrays. Mol Cell. 1999, 4: 649-655. 10.1016/S1097-2765(00)80216-6. Utley RT, Ikeda K, Grant PA, Cote J, Steger DJ, Eberharter A, John S, Workman JL: Transcriptional activators direct histone acetyltransferase complexes to nucleosomes. Nature. 1998, 394: 498-502. 10.1038/28886. Kundu TK, Palhan VB, Wang Z, An W, Cole PA, Roeder RG: Activator-dependent transcription from chromatin in vitro involving targeted histone acetylation by p300. Mol Cell. 2000, 6: 551-561. 10.1016/S1097-2765(00)00054-X. Kraus WL, Manning ET, Kadonaga JT: Biochemical analysis of distinct activation functions in p300 that enhance transcription initiation with chromatin templates. Mol Cell Biol. 1999, 19: 8123-8135. Barlev NA, Candau R, Wang L, Darpino P, Silverman N, Berger SL: Characterization of physical interactions of the putative transcriptional adaptor, ADA2, with acidic activation domains and TATA-binding protein. J Biol Chem. 1995, 270: 19337-19344. 10.1074/jbc.270.33.19337. Kutluay SB, DeVos SL, Klomp JE, Triezenberg SJ: Transcriptional coactivators are not required for herpes simplex virus type 1 immediate-early gene expression in vitro. J Virol. 2009, 83: 3436-3449. 10.1128/JVI.02349-08. Roizman B, Sears AE: An inquiry into the mechanisms of herpes simplex virus latency. Annu Rev Microbiol. 1987, 41: 543-571. 10.1146/annurev.mi.41.100187.002551. Kristie TM, Vogel JL, Sears AE: Nuclear localization of the C1 factor (host cell factor) in sensory neurons correlates with reactivation of herpes simplex virus from latency. Proc Natl Acad Sci USA. 1999, 96: 1229-1233. 10.1073/pnas.96.4.1229. LaBoissiere S, O'Hare P: Analysis of HCF, the cellular cofactor of VP16, in herpes simplex virus-infected cells. J Virol. 2000, 74: 99-109. 10.1128/JVI.74.1.99-109.2000. Lu R, Misra V: Zhangfei: a second cellular protein interacts with herpes simplex virus accessory factor HCF in a manner similar to Luman and VP16. Nucleic Acids Res. 2000, 28: 2446-2454. 10.1093/nar/28.12.2446. Akhova O, Bainbridge M, Misra V: The neuronal host cell factor-binding protein Zhangfei inhibits herpes simplex virus replication. J Virol. 2005, 79: 14708-14718. 10.1128/JVI.79.23.14708-14718.2005. Lu R, Yang P, O'Hare P, Misra V: Luman, a new member of the CREB/ATF family, binds to herpes simplex virus VP16-associated host cellular factor. Mol Cell Biol. 1997, 17: 5117-5126. Lu R, Misra V: Potential role for luman, the cellular homologue of herpes simplex virus VP16 (alpha gene trans-inducing factor), in herpesvirus latency. J Virol. 2000, 74: 934-943. 10.1128/JVI.74.2.934-943.2000. Kolb G, Kristie TM: Association of the cellular coactivator HCF-1 with the Golgi apparatus in sensory neurons. J Virol. 2008, 82: 9555-9563. 10.1128/JVI.01174-08. Cliffe AR, Garber DA, Knipe DM: Transcription of the herpes simplex virus latency-associated transcript promotes the formation of facultative heterochromatin on lytic promoters. J Virol. 2009, 83: 8182-8190. 10.1128/JVI.00712-09. Wang QY, Zhou C, Johnson KE, Colgrove RC, Coen DM, Knipe DM: Herpesviral latency-associated transcript gene promotes assembly of heterochromatin on viral lytic-gene promoters in latent infection. Proc Natl Acad Sci USA. 2005, 102: 16055-16059. 10.1073/pnas.0505850102. Deshmane SL, Fraser NW: During latency, herpes simplex virus type 1 DNA is associated with nucleosomes in a chromatin structure. J Virol. 1989, 63: 943-947. Nogueira ML, Wang VE, Tantin D, Sharp PA, Kristie TM: Herpes simplex virus infections are arrested in Oct-1-deficient cells. Proc Natl Acad Sci USA. 2004, 101: 1473-1478. 10.1073/pnas.0307300101. He X, Treacy MN, Simmons DM, Ingraham HA, Swanson LW, Rosenfeld MG: Expression of a large family of POU-domain regulatory genes in mammalian brain development. Nature. 1989, 340: 35-41. 10.1038/340035a0. Stevens JG, Wagner EK, Devi-Rao GB, Cook ML, Feldman LT: RNA complementary to a herpesvirus alpha gene mRNA is prominent in latently infected neurons. Science. 1987, 235: 1056-1059. 10.1126/science.2434993. Batchelor AH, O'Hare P: Regulation and cell-type-specific activity of a promoter located upstream of the latency-associated transcript of herpes simplex virus type 1. J Virol. 1990, 64: 3269-3279. Zwaagstra JC, Ghiasi H, Slanina SM, Nesburn AB, Wheatley SC, Lillycrop K, Wood J, Latchman DS, Patel K, Wechsler SL: Activity of herpes simplex virus type 1 latency-associated transcript (LAT) promoter in neuron-derived cells: evidence for neuron specificity and for a large LAT transcript. J Virol. 1990, 64: 5019-5028. Kubat NJ, Amelio AL, Giordani NV, Bloom DC: The herpes simplex virus type 1 latency-associated transcript (LAT) enhancer/rcr is hyperacetylated during latency independently of LAT transcription. J Virol. 2004, 78: 12508-12518. 10.1128/JVI.78.22.12508-12518.2004. Drolet BS, Perng GC, Cohen J, Slanina SM, Yukht A, Nesburn AB, Wechsler SL: The region of the herpes simplex virus type 1 LAT gene involved in spontaneous reactivation does not encode a functional protein. Virology. 1998, 242: 221-232. 10.1006/viro.1997.9020. Umbach JL, Kramer MF, Jurak I, Karnowski HW, Coen DM, Cullen BR: MicroRNAs expressed by herpes simplex virus 1 during latent infection regulate viral mRNAs. Nature. 2008, 454: 780-783. Umbach JL, Nagel MA, Cohrs RJ, Gilden DH, Cullen BR: Analysis of human alphaherpesvirus microRNA expression in latently infected human trigeminal ganglia. J Virol. 2009, 83: 10677-10683. 10.1128/JVI.01185-09. Jurak I, Kramer MF, Mellor JC, van Lint AL, Roth FP, Knipe DM, Coen DM: Numerous conserved and divergent microRNAs expressed by herpes simplex viruses 1 and 2. J Virol. 2010, 84: 4659-4672. 10.1128/JVI.02725-09. Cui C, Griffiths A, Li G, Silva LM, Kramer MF, Gaasterland T, Wang XJ, Coen DM: Prediction and identification of herpes simplex virus 1-encoded microRNAs. J Virol. 2006, 80: 5499-5508. 10.1128/JVI.00200-06. Tang S, Bertke AS, Patel A, Wang K, Cohen JI, Krause PR: An acutely and latently expressed herpes simplex virus 2 viral microRNA inhibits expression of ICP34.5, a viral neurovirulence factor. Proc Natl Acad Sci USA. 2008, 105: 10931-10936. 10.1073/pnas.0801845105. Tang S, Patel A, Krause PR: Novel less-abundant viral microRNAs encoded by herpes simplex virus 2 latency-associated transcript and their roles in regulating ICP34.5 and ICP0 mRNAs. J Virol. 2009, 83: 1433-1442. 10.1128/JVI.01723-08. Everett RD: Trans activation of transcription by herpes virus products: requirement for two HSV-1 immediate-early polypeptides for maximum activity. Embo J. 1984, 3: 3135-3141. Gelman IH, Silverstein S: Identification of immediate early genes from herpes simplex virus that transactivate the virus thymidine kinase gene. Proc Natl Acad Sci USA. 1985, 82: 5265-5269. 10.1073/pnas.82.16.5265. O'Hare P, Hayward GS: Evidence for a direct role for both the 175,000- and 110,000-molecular-weight immediate-early proteins of herpes simplex virus in the transactivation of delayed-early promoters. J Virol. 1985, 53: 751-760. Quinlan MP, Knipe DM: Stimulation of expression of a herpes simplex virus DNA-binding protein by two viral functions. Mol Cell Biol. 1985, 5: 957-963. Grewal SI, Jia S: Heterochromatin revisited. Nat Rev Genet. 2007, 8: 35-46. 10.1038/nrg2008. Lomonte P, Thomas J, Texier P, Caron C, Khochbin S, Epstein AL: Functional interaction between class II histone deacetylases and ICP0 of herpes simplex virus type 1. J Virol. 2004, 78: 6744-6757. 10.1128/JVI.78.13.6744-6757.2004. Gu H, Liang Y, Mandel G, Roizman B: Components of the REST/CoREST/histone deacetylase repressor complex are disrupted, modified, and translocated in HSV-1-infected cells. Proc Natl Acad Sci USA. 2005, 102: 7571-7576. 10.1073/pnas.0502658102. Gu H, Roizman B: Herpes simplex virus-infected cell protein 0 blocks the silencing of viral DNA by dissociating histone deacetylases from the CoREST-REST complex. Proc Natl Acad Sci USA. 2007, 104: 17134-17139. 10.1073/pnas.0707266104. Perng GC, Jones C, Ciacci-Zanella J, Stone M, Henderson G, Yukht A, Slanina SM, Hofman FM, Ghiasi H, Nesburn AB, Wechsler SL: Virus-induced neuronal apoptosis blocked by the herpes simplex virus latency-associated transcript. Science. 2000, 287: 1500-1503. 10.1126/science.287.5457.1500. Thompson RL, Sawtell NM: The herpes simplex virus type 1 latency-associated transcript gene regulates the establishment of latency. J Virol. 1997, 71: 5432-5440. Leib DA, Bogard CL, Kosz-Vnenchak M, Hicks KA, Coen DM, Knipe DM, Schaffer PA: A deletion mutant of the latency-associated transcript of herpes simplex virus type 1 reactivates from the latent state with reduced frequency. J Virol. 1989, 63: 2893-2900. Kosz-Vnenchak M, Jacobson J, Coen DM, Knipe DM: Evidence for a novel regulatory pathway for herpes simplex virus gene expression in trigeminal ganglion neurons. J Virol. 1993, 67: 5383-5393. Cai WZ, Schaffer PA: Herpes simplex virus type 1 ICP0 plays a critical role in the de novo synthesis of infectious virus following transfection of viral DNA. J Virol. 1989, 63: 4579-4589. Leib DA, Coen DM, Bogard CL, Hicks KA, Yager DR, Knipe DM, Tyler KL, Schaffer PA: Immediate-early regulatory gene mutants define different stages in the establishment and reactivation of herpes simplex virus latency. J Virol. 1989, 63: 759-768. Jordan R, Schaffer PA: Activation of gene expression by herpes simplex virus type 1 ICP0 occurs at the level of mRNA synthesis. J Virol. 1997, 71: 6850-6862. Pesola JM, Zhu J, Knipe DM, Coen DM: Herpes simplex virus 1 immediate-early and early gene expression during reactivation from latency under conditions that prevent infectious virus production. J Virol. 2005, 79: 14516-14525. 10.1128/JVI.79.23.14516-14525.2005. Cai W, Astor TL, Liptak LM, Cho C, Coen DM, Schaffer PA: The herpes simplex virus type 1 regulatory protein ICP0 enhances virus replication during acute infection and reactivation from latency. J Virol. 1993, 67: 7501-7512. Halford WP, Schaffer PA: ICP0 is required for efficient reactivation of herpes simplex virus type 1 from neuronal latency. J Virol. 2001, 75: 3240-3249. 10.1128/JVI.75.7.3240-3249.2001. Stow ND, Stow EC: Isolation and characterization of a herpes simplex virus type 1 mutant containing a deletion within the gene encoding the immediate early polypeptide Vmw110. J Gen Virol. 1986, 67 (Pt 12): 2571-2585. 10.1099/0022-1317-67-12-2571. Sacks WR, Schaffer PA: Deletion mutants in the gene encoding the herpes simplex virus type 1 immediate-early protein ICP0 exhibit impaired growth in cell culture. J Virol. 1987, 61: 829-839. Thompson RL, Sawtell NM: Evidence that the herpes simplex virus type 1 ICP0 protein does not initiate reactivation from latency in vivo. J Virol. 2006, 80: 10919-10930. 10.1128/JVI.01253-06. Thompson RL, Preston CM, Sawtell NM: De novo synthesis of VP16 coordinates the exit from HSV latency in vivo. PLoS Pathog. 2009, 5: e1000352-10.1371/journal.ppat.1000352. Steiner I, Spivack JG, Deshmane SL, Ace CI, Preston CM, Fraser NW: A herpes simplex virus type 1 mutant containing a nontransinducing Vmw65 protein establishes latent infection in vivo in the absence of viral replication and reactivates efficiently from explanted trigeminal ganglia. J Virol. 1990, 64: 1630-1638. Ecob-Prince MS, Rixon FJ, Preston CM, Hassan K, Kennedy PG: Reactivation in vivo and in vitro of herpes simplex virus from mouse dorsal root ganglia which contain different levels of latency-associated transcripts. J Gen Virol. 1993, 74 (Pt 6): 995-1002. 10.1099/0022-1317-74-6-995. Sawtell NM: Quantitative analysis of herpes simplex virus reactivation in vivo demonstrates that reactivation in the nervous system is not inhibited at early times postinoculation. J Virol. 2003, 77: 4127-4138. 10.1128/JVI.77.7.4127-4138.2003. Sawtell NM, Thompson RL, Haas RL: Herpes simplex virus DNA synthesis is not a decisive regulatory event in the initiation of lytic viral protein expression in neurons in vivo during primary infection or reactivation from latency. J Virol. 2006, 80: 38-50. 10.1128/JVI.80.1.38-50.2006. Petrucelli A, Rak M, Grainger L, Goodrum F: Characterization of a novel Golgi apparatus-localized latency determinant encoded by human cytomegalovirus. J Virol. 2009, 83: 5615-5629. 10.1128/JVI.01989-08. Cheung AK, Abendroth A, Cunningham AL, Slobedman B: Viral gene expression during the establishment of human cytomegalovirus latent infection in myeloid progenitor cells. Blood. 2006, 108: 3691-3699. 10.1182/blood-2005-12-026682. Jenkins C, Abendroth A, Slobedman B: A novel viral transcript with homology to human interleukin-10 is expressed during latent human cytomegalovirus infection. J Virol. 2004, 78: 1440-1447. 10.1128/JVI.78.3.1440-1447.2004. Bego M, Maciejewski J, Khaiboullina S, Pari G, St Jeor S: Characterization of an antisense transcript spanning the UL81-82 locus of human cytomegalovirus. J Virol. 2005, 79: 11022-11034. 10.1128/JVI.79.17.11022-11034.2005. Goodrum FD, Jordan CT, High K, Shenk T: Human cytomegalovirus gene expression during infection of primary hematopoietic progenitor cells: a model for latency. Proc Natl Acad Sci USA. 2002, 99: 16255-16260. 10.1073/pnas.252630899. Schierling K, Stamminger T, Mertens T, Winkler M: Human cytomegalovirus tegument proteins ppUL82 (pp71) and ppUL35 interact and cooperatively activate the major immediate-early enhancer. J Virol. 2004, 78: 9512-9523. 10.1128/JVI.78.17.9512-9523.2004. Stamminger T, Gstaiger M, Weinzierl K, Lorz K, Winkler M, Schaffner W: Open reading frame UL26 of human cytomegalovirus encodes a novel tegument protein that contains a strong transcriptional activation domain. J Virol. 2002, 76: 4836-4847. 10.1128/JVI.76.10.4836-4847.2002. Cristea IM, Moorman NJ, Terhune SS, Cuevas CD, O'Keefe ES, Rout MP, Chait BT, Shenk T: Human cytomegalovirus pUL83 stimulates activity of the viral immediate-early promoter through its interaction with the cellular IFI16 protein. J Virol. 2010, 84: 7803-7814. 10.1128/JVI.00139-10. Terhune SS, Moorman NJ, Cristea IM, Savaryn JP, Cuevas-Bennett C, Rout MP, Chait BT, Shenk T: Human cytomegalovirus UL29/28 protein interacts with components of the NuRD complex which promote accumulation of immediate-early RNA. PLoS Pathog. 2010, 6: e1000965-10.1371/journal.ppat.1000965. Liu B, Stinski MF: Human cytomegalovirus contains a tegument protein that enhances transcription from promoters with upstream ATF and AP-1 cis-acting elements. J Virol. 1992, 66: 4434-4444. Saffert RT, Kalejta RF: Inactivating a cellular intrinsic immune defense mediated by Daxx is the mechanism through which the human cytomegalovirus pp71 protein stimulates viral immediate-early gene expression. J Virol. 2006, 80: 3863-3871. 10.1128/JVI.80.8.3863-3871.2006. Preston CM, Nicholl MJ: Role of the cellular protein hDaxx in human cytomegalovirus immediate-early gene expression. J Gen Virol. 2006, 87: 1113-1121. 10.1099/vir.0.81566-0. Saffert R, Kalejta R: Promyelocytic leukemia-nuclear body proteins: herpesvirus enemies, accomplices, or both?. Future Virology. 2008, 3: 265-277. 10.2217/17460794.3.3.265. Tavalai N, Papior P, Rechter S, Leis M, Stamminger T: Evidence for a role of the cellular ND10 protein PML in mediating intrinsic immunity against human cytomegalovirus infections. J Virol. 2006, 80: 8006-8018. 10.1128/JVI.00743-06. Tavalai N, Papior P, Rechter S, Stamminger T: Nuclear domain 10 components promyelocytic leukemia protein and hDaxx independently contribute to an intrinsic antiviral defense against human cytomegalovirus infection. J Virol. 2008, 82: 126-137. 10.1128/JVI.01685-07. Tavalai N, Stamminger T: Intrinsic cellular defense mechanisms targeting human cytomegalovirus. Virus Res. Ishov AM, Vladimirova OV, Maul GG: Daxx-mediated accumulation of human cytomegalovirus tegument protein pp71 at ND10 facilitates initiation of viral infection at these nuclear domains. J Virol. 2002, 76: 7705-7712. 10.1128/JVI.76.15.7705-7712.2002. Saffert RT, Kalejta RF: Human cytomegalovirus gene expression is silenced by Daxx-mediated intrinsic immune defense in model latent infections established in vitro. J Virol. 2007, 81: 9109-9120. 10.1128/JVI.00827-07. Saffert RT, Penkert RR, Kalejta RF: Cellular and viral control over the initial events of human cytomegalovirus experimental latency in CD34+ cells. J Virol. 2010, 84: 5594-5604. 10.1128/JVI.00348-10. Cantrell SR, Bresnahan WA: Interaction between the human cytomegalovirus UL82 gene product (pp71) and hDaxx regulates immediate-early gene expression and viral replication. J Virol. 2005, 79: 7792-7802. 10.1128/JVI.79.12.7792-7802.2005. Hwang J, Kalejta RF: Proteasome-dependent, ubiquitin-independent degradation of Daxx by the viral pp71 protein in human cytomegalovirus-infected cells. Virology. 2007, 367: 334-338. 10.1016/j.virol.2007.05.037. Hwang J, Kalejta RF: Human cytomegalovirus protein pp71 induces Daxx SUMOylation. J Virol. 2009, 83: 6591-6598. 10.1128/JVI.02639-08. Woodhall DL, Groves IJ, Reeves MB, Wilkinson G, Sinclair JH: Human Daxx-mediated repression of human cytomegalovirus gene expression correlates with a repressive chromatin structure around the major immediate early promoter. J Biol Chem. 2006, 281: 37652-37660. 10.1074/jbc.M604273200. Maxwell KL, Frappier L: Viral proteomics. Microbiol Mol Biol Rev. 2007, 71: 398-411. 10.1128/MMBR.00042-06. Groves IJ, Reeves MB, Sinclair JH: Lytic infection of permissive cells with human cytomegalovirus is regulated by an intrinsic 'pre-immediate-early' repression of viral gene expression mediated by histone post-translational modification. J Gen Virol. 2009, 90: 2364-2374. 10.1099/vir.0.012526-0. Nitzsche A, Paulus C, Nevels M: Temporal dynamics of cytomegalovirus chromatin assembly in productively infected human cells. J Virol. 2008, 82: 11167-11180. 10.1128/JVI.01218-08. Murphy JC, Fischle W, Verdin E, Sinclair JH: Control of cytomegalovirus lytic gene expression by histone acetylation. Embo J. 2002, 21: 1112-1120. 10.1093/emboj/21.5.1112. Reeves MB, Lehner PJ, Sissons JG, Sinclair JH: An in vitro model for the regulation of human cytomegalovirus latency and reactivation in dendritic cells by chromatin remodelling. J Gen Virol. 2005, 86: 2949-2954. 10.1099/vir.0.81161-0. Reeves MB, MacAry PA, Lehner PJ, Sissons JG, Sinclair JH: Latency, chromatin remodeling, and reactivation of human cytomegalovirus in the dendritic cells of healthy carriers. Proc Natl Acad Sci USA. 2005, 102: 4140-4145. 10.1073/pnas.0408994102. Ioudinkova E, Arcangeletti MC, Rynditch A, De Conto F, Motta F, Covan S, Pinardi F, Razin SV, Chezzi C: Control of human cytomegalovirus gene expression by differential histone modifications during lytic and latent infection of a monocytic cell line. Gene. 2006, 384: 120-128. 10.1016/j.gene.2006.07.021. Cuevas-Bennett C, Shenk T: Dynamic histone H3 acetylation and methylation at human cytomegalovirus promoters during replication in fibroblasts. J Virol. 2008, 82: 9525-9536. 10.1128/JVI.00946-08. Dosa R, Burian K, Gonczol E: Human cytomegalovirus latency is associated with the state of differentiation of the host cells: an in vitro model in teratocarcinoma cells. Acta Microbiol Immunol Hung. 2005, 52: 397-406. 10.1556/AMicr.52.2005.3-4.11. Lukashchuk V, McFarlane S, Everett RD, Preston CM: Human cytomegalovirus protein pp71 displaces the chromatin-associated factor ATRX from nuclear domain 10 at early stages of infection. J Virol. 2008, 82: 12543-12554. 10.1128/JVI.01215-08. Gibbons RJ, McDowell TL, Raman S, O'Rourke DM, Garrick D, Ayyub H, Higgs DR: Mutations in ATRX, encoding a SWI/SNF-like protein, cause diverse changes in the pattern of DNA methylation. Nat Genet. 2000, 24: 368-371. 10.1038/74191. Xue Y, Gibbons R, Yan Z, Yang D, McDowell TL, Sechi S, Qin J, Zhou S, Higgs D, Wang W: The ATRX syndrome protein forms a chromatin-remodeling complex with Daxx and localizes in promyelocytic leukemia nuclear bodies. Proc Natl Acad Sci USA. 2003, 100: 10635-10640. 10.1073/pnas.1937626100. Yuan J, Liu X, Wu AW, McGonagill PW, Keller MJ, Galle CS, Meier JL: Breaking human cytomegalovirus major immediate-early gene silence by vasoactive intestinal peptide stimulation of the protein kinase A-CREB-TORC2 signaling cascade in human pluripotent embryonal NTera2 cells. J Virol. 2009, 83: 6391-6403. 10.1128/JVI.00061-09. Liu X, Yuan J, Wu AW, McGonagill PW, Galle CS, Meier JL: Phorbol ester-induced human cytomegalovirus major immediate-early (MIE) enhancer activation through PKC-delta, CREB, and NF-kappaB desilences MIE gene expression in quiescently infected human pluripotent NTera2 cells. J Virol. 2010, 84: 8495-8508. 10.1128/JVI.00416-10. Penkert RR, Kalejta RF: Nuclear localization of tegument-delivered pp71 in human cytomegalovirus-infected cells is facilitated by one or more factors present in terminally differentiated fibroblasts. J Virol. 2010, 84: 9853-9863. 10.1128/JVI.00500-10. Cha TA, Tom E, Kemble GW, Duke GM, Mocarski ES, Spaete RR: Human cytomegalovirus clinical isolates carry at least 19 genes not found in laboratory strains. J Virol. 1996, 70: 78-83. Dolan A, Cunningham C, Hector RD, Hassan-Walker AF, Lee L, Addison C, Dargan DJ, McGeoch DJ, Gatherer D, Emery VC, et al: Genetic content of wild-type human cytomegalovirus. J Gen Virol. 2004, 85: 1301-1312. 10.1099/vir.0.79888-0. Murphy E, Yu D, Grimwood J, Schmutz J, Dickson M, Jarvis MA, Hahn G, Nelson JA, Myers RM, Shenk TE: Coding potential of laboratory and clinical strains of human cytomegalovirus. Proc Natl Acad Sci USA. 2003, 100: 14976-14981. 10.1073/pnas.2136652100. Morissette G, Flamand L: Herpesviruses and chromosomal integration. J Virol. 2010, 84: 12100-12109. 10.1128/JVI.01169-10. Luppi M, Barozzi P, Morris CM, Merelli E, Torelli G: Integration of human herpesvirus 6 genome in human chromosomes. Lancet. 1998, 352: 1707-1708. 10.1016/S0140-6736(05)61483-3. Arbuckle JH, Medveczky MM, Luka J, Hadley SH, Luegmayr A, Ablashi D, Lund TC, Tolar J, De Meirleir K, Montoya JG, et al: The latent human herpesvirus-6A genome specifically integrates in telomeres of human chromosomes in vivo and in vitro. Proc Natl Acad Sci USA. 2010, 107: 5563-5568. 10.1073/pnas.0913586107. Bolovan-Fritts CA, Mocarski ES, Wiedeman JA: Peripheral blood CD14(+) cells from healthy subjects carry a circular conformation of latent cytomegalovirus genome. Blood. 1999, 93: 394-398. Kondo K, Xu J, Mocarski ES: Human cytomegalovirus latent gene expression in granulocyte-macrophage progenitors in culture and in seropositive individuals. Proc Natl Acad Sci USA. 1996, 93: 11137-11142. 10.1073/pnas.93.20.11137. Kondo K, Mocarski ES: Cytomegalovirus latency and latency-specific transcription in hematopoietic progenitors. Scand J Infect Dis Suppl. 1995, 99: 63-67. Landini MP, Lazzarotto T, Xu J, Geballe AP, Mocarski ES: Humoral immune response to proteins of human cytomegalovirus latency-associated transcripts. Biol Blood Marrow Transplant. 2000, 6: 100-108. 10.1016/S1083-8791(00)70072-3. White KL, Slobedman B, Mocarski ES: Human cytomegalovirus latency-associated protein pORF94 is dispensable for productive and latent infection. J Virol. 2000, 74: 9333-9337. 10.1128/JVI.74.19.9333-9337.2000. Chee MS, Bankier AT, Beck S, Bohni R, Brown CM, Cerny R, Horsnell T, Hutchison CA, Kouzarides T, Martignetti JA, et al: Analysis of the protein-coding content of the sequence of human cytomegalovirus strain AD169. Curr Top Microbiol Immunol. 1990, 154: 125-169. Zipeto D, Bodaghi B, Laurent L, Virelizier JL, Michelson S: Kinetics of transcription of human cytomegalovirus chemokine receptor US28 in different cell types. J Gen Virol. 1999, 80 (Pt 3): 543-547. Jenkins C, Garcia W, Godwin MJ, Spencer JV, Stern JL, Abendroth A, Slobedman B: Immunomodulatory properties of a viral homolog of human interleukin-10 expressed by human cytomegalovirus during the latent phase of infection. J Virol. 2008, 82: 3736-3750. 10.1128/JVI.02173-07. Cheung AK, Gottlieb DJ, Plachter B, Pepperl-Klindworth S, Avdic S, Cunningham AL, Abendroth A, Slobedman B: The role of the human cytomegalovirus UL111A gene in down-regulating CD4+ T-cell recognition of latently infected cells: implications for virus elimination during latency. Blood. 2009, 114: 4128-4137. 10.1182/blood-2008-12-197111. Reeves MB, Sinclair JH: Analysis of latent viral gene expression in natural and experimental latency models of human cytomegalovirus and its correlation with histone modifications at a latent promoter. J Gen Virol. 2010, 91: 599-604. 10.1099/vir.0.015602-0. Goodrum F, Reeves M, Sinclair J, High K, Shenk T: Human cytomegalovirus sequences expressed in latently infected individuals promote a latent infection in vitro. Blood. 2007, 110: 937-945. 10.1182/blood-2007-01-070078. Murphy E, Vanicek J, Robins H, Shenk T, Levine AJ: Suppression of immediate-early viral gene expression by herpesvirus-coded microRNAs: implications for latency. Proc Natl Acad Sci USA. 2008, 105: 5453-5458. 10.1073/pnas.0711910105. Grey F, Meyers H, White EA, Spector DH, Nelson J: A human cytomegalovirus-encoded microRNA regulates expression of multiple viral genes involved in replication. PLoS Pathog. 2007, 3: e163-10.1371/journal.ppat.0030163. Hertel L, Lacaille VG, Strobl H, Mellins ED, Mocarski ES: Susceptibility of immature and mature Langerhans cell-type dendritic cells to infection and immunomodulation by human cytomegalovirus. J Virol. 2003, 77: 7563-7574. 10.1128/JVI.77.13.7563-7574.2003. Soderberg-Naucler C, Fish KN, Nelson JA: Reactivation of latent human cytomegalovirus by allogeneic stimulation of blood cells from healthy donors. Cell. 1997, 91: 119-126. 10.1016/S0092-8674(01)80014-3. Maciejewski JP, St Jeor SC: Human cytomegalovirus infection of human hematopoietic progenitor cells. Leuk Lymphoma. 1999, 33: 1-13. Soderberg-Naucler C, Streblow DN, Fish KN, Allan-Yorke J, Smith PP, Nelson JA: Reactivation of latent human cytomegalovirus in CD14(+) monocytes is differentiation dependent. J Virol. 2001, 75: 7543-7554. 10.1128/JVI.75.16.7543-7554.2001. Kuppers R: B cells under influence: transformation of B cells by Epstein-Barr virus. Nat Rev Immunol. 2003, 3: 801-812. 10.1038/nri1201. Jiang R, Scott RS, Hutt-Fletcher LM: Epstein-Barr virus shed in saliva is high in B-cell-tropic glycoprotein gp42. J Virol. 2006, 80: 7281-7283. 10.1128/JVI.00497-06. Cohen JI: Epstein-Barr virus infection. N Engl J Med. 2000, 343: 481-492. 10.1056/NEJM200008173430707. Shannon-Lowe CD, Neuhierl B, Baldwin G, Rickinson AB, Delecluse HJ: Resting B cells as a transfer vehicle for Epstein-Barr virus infection of epithelial cells. Proc Natl Acad Sci USA. 2006, 103: 7065-7070. 10.1073/pnas.0510512103. Shannon-Lowe C, Adland E, Bell AI, Delecluse HJ, Rickinson AB, Rowe M: Features distinguishing Epstein-Barr virus infections of epithelial cells and B cells: viral genome expression, genome maintenance, and genome amplification. J Virol. 2009, 83: 7749-7760. 10.1128/JVI.00108-09. Li QX, Young LS, Niedobitek G, Dawson CW, Birkenbach M, Wang F, Rickinson AB: Epstein-Barr virus infection and replication in a human epithelial cell system. Nature. 1992, 356: 347-350. 10.1038/356347a0. Altmann M, Hammerschmidt W: Epstein-Barr virus provides a new paradigm: a requirement for the immediate inhibition of apoptosis. PLoS Biol. 2005, 3: e404-10.1371/journal.pbio.0030404. Kalla M, Schmeinck A, Bergbauer M, Pich D, Hammerschmidt W: AP-1 homolog BZLF1 of Epstein-Barr virus has two essential functions dependent on the epigenetic state of the viral genome. Proc Natl Acad Sci USA. 2010, 107: 850-855. 10.1073/pnas.0911948107. Wen W, Iwakiri D, Yamamoto K, Maruo S, Kanda T, Takada K: Epstein-Barr virus BZLF1 gene, a switch from latency to lytic infection, is expressed as an immediate-early gene after primary infection of B lymphocytes. J Virol. 2007, 81: 1037-1042. 10.1128/JVI.01416-06. Kelly GL, Long HM, Stylianou J, Thomas WA, Leese A, Bell AI, Bornkamm GW, Mautner J, Rickinson AB, Rowe M: An Epstein-Barr virus anti-apoptotic protein constitutively expressed in transformed cells and implicated in burkitt lymphomagenesis: the Wp/BHRF1 link. PLoS Pathog. 2009, 5: e1000341-10.1371/journal.ppat.1000341. Halder S, Murakami M, Verma SC, Kumar P, Yi F, Robertson ES: Early events associated with infection of Epstein-Barr virus infection of primary B-cells. PLoS One. 2009, 4: e7214-10.1371/journal.pone.0007214. Farrell PJ, Rowe DT, Rooney CM, Kouzarides T: Epstein-Barr virus BZLF1 trans-activator specifically binds to a consensus AP-1 site and is related to c-fos. Embo J. 1989, 8: 127-132. Hong GK, Gulley ML, Feng WH, Delecluse HJ, Holley-Guthrie E, Kenney SC: Epstein-Barr virus lytic infection contributes to lymphoproliferative disease in a SCID mouse model. J Virol. 2005, 79: 13993-14003. 10.1128/JVI.79.22.13993-14003.2005. Chipuk JE, Moldoveanu T, Llambi F, Parsons MJ, Green DR: The BCL-2 family reunion. Mol Cell. 2010, 37: 299-310. 10.1016/j.molcel.2010.01.025. Bellows DS, Howell M, Pearson C, Hazlewood SA, Hardwick JM: Epstein-Barr virus BALF1 is a BCL-2-like antagonist of the herpesvirus antiapoptotic BCL-2 proteins. J Virol. 2002, 76: 2469-2479. 10.1128/jvi.76.5.2469-2479.2002. Oudejans JJ, van den Brule AJ, Jiwa NM, de Bruin PC, Ossenkoppele GJ, van der Valk P, Walboomers JM, Meijer CJ: BHRF1, the Epstein-Barr virus (EBV) homologue of the BCL-2 protooncogene, is transcribed in EBV-associated B-cell lymphomas and in reactive lymphocytes. Blood. 1995, 86: 1893-1902. Seto E, Moosmann A, Gromminger S, Walz N, Grundhoff A, Hammerschmidt W: Micro RNAs of Epstein-Barr virus promote cell cycle progression and prevent apoptosis of primary human B cells. PLoS Pathog. 2010, 6: e1001063-10.1371/journal.ppat.1001063. pii Swaminathan S: Noncoding RNAs produced by oncogenic human herpesviruses. J Cell Physiol. 2008, 216: 321-326. 10.1002/jcp.21480. Speck SH, Chatila T, Flemington E: Reactivation of Epstein-Barr virus: regulation and function of the BZLF1 gene. Trends Microbiol. 1997, 5: 399-405. 10.1016/S0966-842X(97)01129-3. Bergbauer M, Kalla M, Schmeinck A, Gobel C, Rothbauer U, Eck S, Benet-Pages A, Strom TM, Hammerschmidt W: CpG-methylation regulates a class of Epstein-Barr virus promoters. PLoS Pathog. 2010, 6: e1001114-10.1371/journal.ppat.1001114. pii Bhende PM, Seaman WT, Delecluse HJ, Kenney SC: The EBV lytic switch protein, Z, preferentially binds to and activates the methylated viral genome. Nat Genet. 2004, 36: 1099-1104. 10.1038/ng1424. Dickerson SJ, Xing Y, Robinson AR, Seaman WT, Gruffat H, Kenney SC: Methylation-dependent binding of the epstein-barr virus BZLF1 protein to viral promoters. PLoS Pathog. 2009, 5: e1000356-10.1371/journal.ppat.1000356. Baldick CJ, Marchini A, Patterson CE, Shenk T: Human cytomegalovirus tegument protein pp71 (ppUL82) enhances the infectivity of viral DNA and accelerates the infectious cycle. J Virol. 1997, 71: 4400-4408. Werstuck G, Bilan P, Capone JP: Enhanced infectivity of herpes simplex virus type 1 viral DNA in a cell line expressing the trans-inducing factor Vmw65. J Virol. 1990, 64: 984-991. Feederle R, Neuhierl B, Baldwin G, Bannert H, Hub B, Mautner J, Behrends U, Delecluse HJ: Epstein-Barr virus BNRF1 protein allows efficient transfer from the endosomal compartment to the nucleus of primary B lymphocytes. J Virol. 2006, 80: 9435-9443. 10.1128/JVI.00473-06. Yates JL, Warren N, Sugden B: Stable replication of plasmids derived from Epstein-Barr virus in various mammalian cells. Nature. 1985, 313: 812-815. 10.1038/313812a0. Kirchmaier AL, Sugden B: Plasmid maintenance of derivatives of oriP of Epstein-Barr virus. J Virol. 1995, 69: 1280-1283. Lindner SE, Sugden B: The plasmid replicon of Epstein-Barr virus: mechanistic insights into efficient, licensed, extrachromosomal replication in human cells. Plasmid. 2007, 58: 1-12. 10.1016/j.plasmid.2007.01.003. Nanbo A, Sugden A, Sugden B: The coupling of synthesis and partitioning of EBV's plasmid replicon is revealed in live cells. Embo J. 2007, 26: 4252-4262. 10.1038/sj.emboj.7601853. Wang J, Lindner SE, Leight ER, Sugden B: Essential elements of a licensed, mammalian plasmid origin of DNA synthesis. Mol Cell Biol. 2006, 26: 1124-1134. 10.1128/MCB.26.3.1124-1134.2006. Speck S: Regulation of EBV Latency-Associated Gene Expression. Epstein-Barr Virus. Edited by: Robertson E. 2005, Portland: Caister Academic Press, 403-427. Speck SH, Ganem D: Viral latency and its regulation: lessons from the gamma-herpesviruses. Cell Host Microbe. 2010, 8: 100-115. 10.1016/j.chom.2010.06.014. Thorley-Lawson DA, Duca KA, Shapiro M: Epstein-Barr virus: a paradigm for persistent infection - for real and in virtual reality. Trends Immunol. 2008, 29: 195-201. 10.1016/j.it.2008.01.006. Kieff E, Rickinson A: Epstein-Barr Virus and Its Replication. Fields Virology. Edited by: Howley P. 2007, Philadelphia: Lippincott, 2603-2654. Bornkamm GW, Hammerschmidt W: Molecular virology of Epstein-Barr virus. Philos Trans R Soc Lond B Biol Sci. 2001, 356: 437-459. 10.1098/rstb.2000.0781. Reisman D, Yates J, Sugden B: A putative origin of replication of plasmids derived from Epstein-Barr virus is composed of two cis-acting components. Mol Cell Biol. 1985, 5: 1822-1832. Sears J, Ujihara M, Wong S, Ott C, Middeldorp J, Aiyar A: The amino terminus of Epstein-Barr Virus (EBV) nuclear antigen 1 contains AT hooks that facilitate the replication and partitioning of latent EBV genomes by tethering them to cellular chromosomes. J Virol. 2004, 78: 11487-11505. 10.1128/JVI.78.21.11487-11505.2004. Iwakiri D, Takada K: Role of EBERs in the pathogenesis of EBV infection. Adv Cancer Res. 2010, 107: 119-136. full_text. Nanbo A, Takada K: The role of Epstein-Barr virus-encoded small RNAs (EBERs) in oncogenesis. Rev Med Virol. 2002, 12: 321-326. 10.1002/rmv.363. Lo AK, To KF, Lo KW, Lung RW, Hui JW, Liao G, Hayward SD: Modulation of LMP1 protein expression by EBV-encoded microRNAs. Proc Natl Acad Sci USA. 2007, 104: 16164-16169. 10.1073/pnas.0702896104. Xia T, O'Hara A, Araujo I, Barreto J, Carvalho E, Sapucaia JB, Ramos JC, Luz E, Pedroso C, Manrique M, et al: EBV microRNAs in primary lymphomas and targeting of CXCL-11 by ebv-mir-BHRF1-3. Cancer Res. 2008, 68: 1436-1442. 10.1158/0008-5472.CAN-07-5126. Takacs M, Banati F, Koroknai A, Segesdi J, Salamon D, Wolf H, Niller HH, Minarovits J: Epigenetic regulation of latent Epstein-Barr virus promoters. Biochim Biophys Acta. 2010, 1799: 228-235. Chau CM, Lieberman PM: Dynamic chromatin boundaries delineate a latency control region of Epstein-Barr virus. J Virol. 2004, 78: 12308-12319. 10.1128/JVI.78.22.12308-12319.2004. Day L, Chau CM, Nebozhyn M, Rennekamp AJ, Showe M, Lieberman PM: Chromatin profiling of Epstein-Barr virus latency control region. J Virol. 2007, 81: 6389-6401. 10.1128/JVI.02172-06. Alazard N, Gruffat H, Hiriart E, Sergeant A, Manet E: Differential hyperacetylation of histones H3 and H4 upon promoter-specific recruitment of EBNA2 in Epstein-Barr virus chromatin. J Virol. 2003, 77: 8166-8172. 10.1128/JVI.77.14.8166-8172.2003. Tempera I, Wiedmer A, Dheekollu J, Lieberman PM: CTCF prevents the epigenetic drift of EBV latency promoter Qp. PLoS Pathog. 2010, 6: e1001048-10.1371/journal.ppat.1001048. pii Chau CM, Zhang XY, McMahon SB, Lieberman PM: Regulation of Epstein-Barr virus latency type by the chromatin boundary factor CTCF. J Virol. 2006, 80: 5723-5732. 10.1128/JVI.00025-06. Yu X, Wang Z, Mertz JE: ZEB1 regulates the latent-lytic switch in infection by Epstein-Barr virus. PLoS Pathog. 2007, 3: e194-10.1371/journal.ppat.0030194. Kraus RJ, Perrigoue JG, Mertz JE: ZEB negatively regulates the lytic-switch BZLF1 gene promoter of Epstein-Barr virus. J Virol. 2003, 77: 199-207. 10.1128/JVI.77.1.199-207.2003. Rodriguez A, Jung EJ, Flemington EK: Cell cycle analysis of Epstein-Barr virus-infected cells following treatment with lytic cycle-inducing agents. J Virol. 2001, 75: 4482-4489. 10.1128/JVI.75.10.4482-4489.2001. Takada K: Cross-linking of cell surface immunoglobulins induces Epstein-Barr virus in Burkitt lymphoma lines. Int J Cancer. 1984, 33: 27-32. 10.1002/ijc.2910330106. Bhende PM, Dickerson SJ, Sun X, Feng WH, Kenney SC: X-box-binding protein 1 activates lytic Epstein-Barr virus gene expression in combination with protein kinase D. J Virol. 2007, 81: 7363-7370. 10.1128/JVI.00154-07. Sun CC, Thorley-Lawson DA: Plasma cell-specific transcription factor XBP-1s binds to and transactivates the Epstein-Barr virus BZLF1 promoter. J Virol. 2007, 81: 13566-13577. 10.1128/JVI.01055-07. Leucci E, Onnis A, Cocco M, De Falco G, Imperatore F, Giuseppina A, Costanzo V, Cerino G, Mannucci S, Cantisani R, et al: B-cell differentiation in EBV-positive Burkitt lymphoma is impaired at posttranscriptional level by miRNA-altered expression. Int J Cancer. 2010, 126: 1316-1326. Biggin M, Bodescot M, Perricaudet M, Farrell P: Epstein-Barr virus gene expression in P3HR1-superinfected Raji cells. J Virol. 1987, 61: 3120-3132. Laux G, Freese UK, Fischer R, Polack A, Kofler E, Bornkamm GW: TPA-inducible Epstein-Barr virus genes in Raji cells and their regulation. Virology. 1988, 162: 503-507. 10.1016/0042-6822(88)90496-5. Adamson AL, Kenney SC: Rescue of the Epstein-Barr virus BZLF1 mutant, Z(S186A), early gene activation defect by the BRLF1 gene product. Virology. 1998, 251: 187-197. 10.1006/viro.1998.9396. Francis AL, Gradoville L, Miller G: Alteration of a single serine in the basic domain of the Epstein-Barr virus ZEBRA protein separates its functions of transcriptional activation and disruption of latency. J Virol. 1997, 71: 3054-3061. Rooney CM, Rowe DT, Ragot T, Farrell PJ: The spliced BZLF1 gene of Epstein-Barr virus (EBV) transactivates an early EBV promoter and induces the virus productive cycle. J Virol. 1989, 63: 3109-3116. Shimizu N, Takada K: Analysis of the BZLF1 promoter of Epstein-Barr virus: identification of an anti-immunoglobulin response sequence. J Virol. 1993, 67: 3240-3245. Ye J, Gradoville L, Miller G: Cellular immediate-early gene expression occurs kinetically upstream of Epstein-Barr virus bzlf1 and brlf1 following cross-linking of the B cell antigen receptor in the Akata Burkitt lymphoma cell line. J Virol. 2010, 84: 12405-12418. 10.1128/JVI.01415-10. Reeves MB: Chromatin-mediated regulation of cytomegalovirus gene expression. Virus Res. Knickelbein JE, Khanna KM, Yee MB, Baty CJ, Kinchington PR, Hendricks RL: Noncytotoxic lytic granule-mediated CD8+ T cell inhibition of HSV-1 reactivation from neuronal latency. Science. 2008, 322: 268-271. 10.1126/science.1164164. van Domselaar R, Philippen LE, Quadir R, Wiertz EJ, Kummer JA, Bovenschen N: Noncytotoxic Inhibition of Cytomegalovirus Replication through NK Cell Protease Granzyme M-Mediated Cleavage of Viral Phosphoprotein 71. J Immunol. 2010, 185: 7605-7613. 10.4049/jimmunol.1001503. Everett RD, Rechter S, Papior P, Tavalai N, Stamminger T, Orr A: PML contributes to a cellular mechanism of repression of herpes simplex virus type 1 infection that is inactivated by ICP0. J Virol. 2006, 80: 7995-8005. 10.1128/JVI.00734-06. Wilkinson GW, Kelly C, Sinclair JH, Rickards C: Disruption of PML-associated nuclear bodies mediated by the human cytomegalovirus major immediate early gene product. J Gen Virol. 1998, 79 (Pt 5): 1233-1245. Korioth F, Maul GG, Plachter B, Stamminger T, Frey J: The nuclear domain 10 (ND10) is disrupted by the human cytomegalovirus gene product IE1. Exp Cell Res. 1996, 229: 155-158. 10.1006/excr.1996.0353. Adamson AL, Kenney S: Epstein-barr virus immediate-early protein BZLF1 is SUMO-1 modified and disrupts promyelocytic leukemia bodies. J Virol. 2001, 75: 2388-2399. 10.1128/JVI.75.5.2388-2399.2001.