1932

Abstract

Herpesvirus gene expression is dynamic and complex, with distinct complements of viral genes expressed at specific times in different infection contexts. These complex patterns of viral gene expression arise in part from the integration of multiple cellular and viral signals that affect the transcription of viral genes. The use of alternative promoters provides an increased level of control, allowing different promoters to direct the transcription of the same gene in response to distinct temporal and contextual cues. While once considered rare, herpesvirus alternative promoter usage was recently found to be far more pervasive and impactful than previously thought. Here we review several examples of promoter switching in herpesviruses and discuss the functional consequences on the transcriptional and post-transcriptional regulation of viral gene expression.

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2021-09-29
2024-06-24
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Literature Cited

  1. 1. 
    Smale ST, Kadonaga JT. 2003. The RNA polymerase II core promoter. Annu. Rev. Biochem. 72:449–79
    [Google Scholar]
  2. 2. 
    Kadonaga JT. 2012. Perspectives on the RNA polymerase II core promoter. Wiley Interdiscip. Rev. Dev. Biol. 1:40–51
    [Google Scholar]
  3. 3. 
    Pugh BF, Tjian R. 1991. Transcription from a TATA-less promoter requires a multisubunit TFIID complex. Genes Dev 5:1935–45
    [Google Scholar]
  4. 4. 
    Cianfrocco MA, Kassavetis GA, Grob P, Fang J, Juven-Gershon T et al. 2013. Human TFIID binds to core promoter DNA in a reorganized structural state. Cell 152:120–31
    [Google Scholar]
  5. 5. 
    Patel AB, Greber BJ, Nogales E. 2020. Recent insights into the structure of TFIID, its assembly, and its binding to core promoter. Curr. Opin. Struct. Biol. 61:17–24
    [Google Scholar]
  6. 6. 
    Lambert SA, Jolma A, Campitelli LF, Das PK, Yin Y et al. 2018. The human transcription factors. Cell 172:650–65
    [Google Scholar]
  7. 7. 
    Lam EW, Brosens JJ, Gomes AR, Koo CY. 2013. Forkhead box proteins: tuning forks for transcriptional harmony. Nat. Rev. Cancer 13:482–95
    [Google Scholar]
  8. 8. 
    Jacob F, Monod J. 1961. Genetic regulatory mechanisms in the synthesis of proteins. J. Mol. Biol. 3:318–56
    [Google Scholar]
  9. 9. 
    Kimura K, Wakamatsu A, Suzuki Y, Ota T, Nishikawa T et al. 2006. Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes. Genome Res 16:55–65
    [Google Scholar]
  10. 10. 
    Davuluri RV, Suzuki Y, Sugano S, Plass C, Huang TH. 2008. The functional consequences of alternative promoter use in mammalian genomes. Trends Genet 24:167–77
    [Google Scholar]
  11. 11. 
    Wright KD, Miller BS, El-Meanawy S, Tsaih SW, Banerjee A et al. 2019. The p52 isoform of SHC1 is a key driver of breast cancer initiation. Breast Cancer Res 21:74
    [Google Scholar]
  12. 12. 
    Prigent SA, Nagane M, Lin H, Huvar I, Boss GR et al. 1996. Enhanced tumorigenic behavior of glioblastoma cells expressing a truncated epidermal growth factor receptor is mediated through the Ras-Shc-Grb2 pathway. J. Biol. Chem. 271:25639–45
    [Google Scholar]
  13. 13. 
    Luzi L, Confalonieri S, Di Fiore PP, Pelicci PG. 2000. Evolution of Shc functions from nematode to human. Curr. Opin. Genet. Dev. 10:668–74
    [Google Scholar]
  14. 14. 
    Lone A, Harris RA, Singh O, Betts DH, Cumming RC. 2018. p66Shc activation promotes increased oxidative phosphorylation and renders CNS cells more vulnerable to amyloid beta toxicity. Sci. Rep. 8:17081
    [Google Scholar]
  15. 15. 
    Ventura A, Luzi L, Pacini S, Baldari CT, Pelicci PG. 2002. The p66Shc longevity gene is silenced through epigenetic modifications of an alternative promoter. J. Biol. Chem. 277:22370–76
    [Google Scholar]
  16. 16. 
    Corley M, Solem A, Phillips G, Lackey L, Ziehr B et al. 2017. An RNA structure-mediated, posttranscriptional model of human α-1-antitrypsin expression. PNAS 114:E10244–53
    [Google Scholar]
  17. 17. 
    Crystal RG. 1989. The α1-antitrypsin gene and its deficiency states. Trends Genet 5:411–17
    [Google Scholar]
  18. 18. 
    Castaldi PJ, Cho MH, Cohn M, Langerman F, Moran S et al. 2010. The COPD genetic association compendium: a comprehensive online database of COPD genetic associations. Hum. Mol. Genet. 19:526–34
    [Google Scholar]
  19. 19. 
    Eden E, Mitchell D, Mehlman B, Khouli H, Nejat M et al. 1997. Atopy, asthma, and emphysema in patients with severe α-1-antitrypysin deficiency. Am. J. Respir. Crit. Care Med. 156:68–74
    [Google Scholar]
  20. 20. 
    Gruffat H, Marchione R, Manet E. 2016. Herpesvirus late gene expression: A viral-specific pre-initiation complex is key. Front. Microbiol. 7:869
    [Google Scholar]
  21. 21. 
    Wyrwicz LS, Rychlewski L. 2007. Identification of herpes TATT-binding protein. Antivir. Res. 75:167–72
    [Google Scholar]
  22. 22. 
    Stinski MF, Thomsen DR, Stenberg RM, Goldstein LC. 1983. Organization and expression of the immediate early genes of human cytomegalovirus. J. Virol. 46:1–14
    [Google Scholar]
  23. 23. 
    Nevels M, Paulus C, Shenk T 2004. Human cytomegalovirus immediate-early 1 protein facilitates viral replication by antagonizing histone deacetylation. PNAS 101:17234–39
    [Google Scholar]
  24. 24. 
    Malone CL, Vesole DH, Stinski MF. 1990. Transactivation of a human cytomegalovirus early promoter by gene products from the immediate-early gene IE2 and augmentation by IE1: mutational analysis of the viral proteins. J. Virol. 64:1498–506
    [Google Scholar]
  25. 25. 
    Caswell R, Hagemeier C, Chiou CJ, Hayward G, Kouzarides T, Sinclair J. 1993. The human cytomegalovirus 86K immediate early (IE) 2 protein requires the basic region of the TATA-box binding protein (TBP) for binding, and interacts with TBP and transcription factor TFIIB via regions of IE2 required for transcriptional regulation. J. Gen. Virol. 74:Part 122691–98
    [Google Scholar]
  26. 26. 
    Lukac DM, Harel NY, Tanese N, Alwine JC. 1997. TAF-like functions of human cytomegalovirus immediate-early proteins. J. Virol. 71:7227–39
    [Google Scholar]
  27. 27. 
    Hermiston TW, Malone CL, Witte PR, Stinski MF. 1987. Identification and characterization of the human cytomegalovirus immediate-early region 2 gene that stimulates gene expression from an inducible promoter. J. Virol. 61:3214–21
    [Google Scholar]
  28. 28. 
    Iwamoto GK, Monick MM, Clark BD, Auron PE, Stinski MF, Hunninghake GW. 1990. Modulation of interleukin 1 beta gene expression by the immediate early genes of human cytomegalovirus. J. Clin. Invest. 85:1853–57
    [Google Scholar]
  29. 29. 
    Geist LJ, Monick MM, Stinski MF, Hunninghake GW. 1992. Cytomegalovirus immediate early genes prevent the inhibitory effect of cyclosporin A on interleukin 2 gene transcription. J. Clin. Invest. 90:2136–40
    [Google Scholar]
  30. 30. 
    Guito J, Lukac DM. 2015. KSHV reactivation and novel implications of protein isomerization on lytic switch control. Viruses 7:72–109
    [Google Scholar]
  31. 31. 
    Gradoville L, Gerlach J, Grogan E, Shedd D, Nikiforow S et al. 2000. 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. J. Virol. 74:6207–12
    [Google Scholar]
  32. 32. 
    Lukac DM, Kirshner JR, Ganem D. 1999. Transcriptional activation by the product of open reading frame 50 of Kaposi's sarcoma-associated herpesvirus is required for lytic viral reactivation in B cells. J. Virol. 73:9348–61
    [Google Scholar]
  33. 33. 
    Sun R, Lin SF, Gradoville L, Yuan Y, Zhu F, Miller G 1998. A viral gene that activates lytic cycle expression of Kaposi's sarcoma-associated herpesvirus. PNAS 95:10866–71
    [Google Scholar]
  34. 34. 
    Smith CA, Bates P, Rivera-Gonzalez R, Gu B, DeLuca NA. 1993. ICP4, the major transcriptional regulatory protein of herpes simplex virus type 1, forms a tripartite complex with TATA-binding protein and TFIIB. J. Virol. 67:4676–87
    [Google Scholar]
  35. 35. 
    Tunnicliffe RB, Lockhart-Cairns MP, Levy C, Mould AP, Jowitt TA et al. 2017. The herpes viral transcription factor ICP4 forms a novel DNA recognition complex. Nucleic Acids Res 45:8064–78
    [Google Scholar]
  36. 36. 
    DeLuca NA, McCarthy AM, Schaffer PA. 1985. Isolation and characterization of deletion mutants of herpes simplex virus type 1 in the gene encoding immediate-early regulatory protein ICP4. J. Virol. 56:558–70
    [Google Scholar]
  37. 37. 
    Godowski PJ, Knipe DM 1986. Transcriptional control of herpesvirus gene expression: gene functions required for positive and negative regulation. PNAS 83:256–60
    [Google Scholar]
  38. 38. 
    Romanowski MJ, Shenk T. 1997. Characterization of the human cytomegalovirus irs1 and trs1 genes: a second immediate-early transcription unit within irs1 whose product antagonizes transcriptional activation. J. Virol. 71:1485–96
    [Google Scholar]
  39. 39. 
    Baldick CJ Jr., Marchini A, Patterson CE, Shenk T. 1997. Human cytomegalovirus tegument protein pp71 (ppUL82) enhances the infectivity of viral DNA and accelerates the infectious cycle. J. Virol. 71:4400–8
    [Google Scholar]
  40. 40. 
    Cristea IM, Moorman NJ, Terhune SS, Cuevas CD, O'Keefe ES et al. 2010. Human cytomegalovirus pUL83 stimulates activity of the viral immediate-early promoter through its interaction with the cellular IFI16 protein. J. Virol. 84:7803–14
    [Google Scholar]
  41. 41. 
    Stasiak PC, Mocarski ES. 1992. Transactivation of the cytomegalovirus ICP36 gene promoter requires the α gene product TRS1 in addition to IE1 and IE2. J. Virol. 66:1050–58
    [Google Scholar]
  42. 42. 
    Dalrymple MA, McGeoch DJ, Davison AJ, Preston CM. 1985. DNA sequence of the herpes simplex virus type 1 gene whose product is responsible for transcriptional activation of immediate early promoters. Nucleic Acids Res 13:7865–79
    [Google Scholar]
  43. 43. 
    Rice SA, Knipe DM. 1990. Genetic evidence for two distinct transactivation functions of the herpes simplex virus α protein ICP27. J. Virol. 64:1704–15
    [Google Scholar]
  44. 44. 
    Wang F, Gregory CD, Rowe M, Rickinson AB, Wang D et al. 1987. Epstein-Barr virus nuclear antigen 2 specifically induces expression of the B-cell activation antigen CD23. PNAS 84:3452–56
    [Google Scholar]
  45. 45. 
    Chevallier-Greco A, Manet E, Chavrier P, Mosnier C, Daillie J, Sergeant A. 1986. Both Epstein-Barr virus (EBV)-encoded trans-acting factors, EB1 and EB2, are required to activate transcription from an EBV early promoter. EMBO J 5:3243–49
    [Google Scholar]
  46. 46. 
    Kalamvoki M, Roizman B. 2010. Role of herpes simplex virus ICP0 in the transactivation of genes introduced by infection or transfection: a reappraisal. J. Virol. 84:4222–28
    [Google Scholar]
  47. 47. 
    Takada K, Shimizu N, Sakuma S, Ono Y. 1986. trans activation of the latent Epstein-Barr virus (EBV) genome after transfection of the EBV DNA fragment. J. Virol. 57:1016–22
    [Google Scholar]
  48. 48. 
    Ragoczy T, Heston L, Miller G. 1998. The Epstein-Barr virus Rta protein activates lytic cycle genes and can disrupt latency in B lymphocytes. J. Virol. 72:7978–84
    [Google Scholar]
  49. 49. 
    Dittmer DP, Damania B. 2016. Kaposi sarcoma-associated herpesvirus: immunobiology, oncogenesis, and therapy. J. Clin. Invest. 126:3165–75
    [Google Scholar]
  50. 50. 
    Bechtel JT, Liang Y, Hvidding J, Ganem D. 2003. Host range of Kaposi's sarcoma-associated herpesvirus in cultured cells. J. Virol. 77:6474–81
    [Google Scholar]
  51. 51. 
    Broussard G, Damania B. 2020. Regulation of KSHV latency and lytic reactivation. Viruses 12:1034
    [Google Scholar]
  52. 52. 
    Wakeman BS, Izumiya Y, Speck SH. 2017. Identification of novel Kaposi's sarcoma-associated herpesvirus Orf50 transcripts: discovery of new RTA isoforms with variable transactivation potential. J. Virol. 91:e01434-16
    [Google Scholar]
  53. 53. 
    Gray KS, Allen RD 3rd, Farrell ML, Forrest JC, Speck SH 2009. Alternatively initiated gene 50/RTA transcripts expressed during murine and human gammaherpesvirus reactivation from latency. J. Virol. 83:314–28
    [Google Scholar]
  54. 54. 
    Wakeman BS, Johnson LS, Paden CR, Gray KS, Virgin HW, Speck SH. 2014. Identification of alternative transcripts encoding the essential murine gammaherpesvirus lytic transactivator RTA. J. Virol. 88:5474–90
    [Google Scholar]
  55. 55. 
    Reese TA, Wakeman BS, Choi HS, Hufford MM, Huang SC et al. 2014. Helminth infection reactivates latent gamma-herpesvirus via cytokine competition at a viral promoter. Science 345:573–77
    [Google Scholar]
  56. 56. 
    Whitehouse A, Carr IM, Griffiths JC, Meredith DM. 1997. The herpesvirus saimiri ORF50 gene, encoding a transcriptional activator homologous to the Epstein-Barr virus R protein, is transcribed from two distinct promoters of different temporal phases. J. Virol. 71:2550–54
    [Google Scholar]
  57. 57. 
    Manet E, Gruffat H, Trescol-Biemont MC, Moreno N, Chambard P et al. 1989. Epstein-Barr virus bicistronic mRNAs generated by facultative splicing code for two transcriptional trans-activators. EMBO J 8:1819–26
    [Google Scholar]
  58. 58. 
    Kedes DH, Lagunoff M, Renne R, Ganem D. 1997. Identification of the gene encoding the major latency-associated nuclear antigen of the Kaposi's sarcoma-associated herpesvirus. J. Clin. Invest. 100:2606–10
    [Google Scholar]
  59. 59. 
    Raab-Traub N. 2012. Novel mechanisms of EBV-induced oncogenesis. Curr. Opin. Virol. 2:453–58
    [Google Scholar]
  60. 60. 
    Tierney RJ, Steven N, Young LS, Rickinson AB. 1994. Epstein-Barr virus latency in blood mononuclear cells: analysis of viral gene transcription during primary infection and in the carrier state. J. Virol. 68:7374–85
    [Google Scholar]
  61. 61. 
    Sample J, Kieff E. 1990. Transcription of the Epstein-Barr virus genome during latency in growth-transformed lymphocytes. J. Virol. 64:1667–74
    [Google Scholar]
  62. 62. 
    Schaefer BC, Strominger JL, Speck SH 1995. Redefining the Epstein-Barr virus-encoded nuclear antigen EBNA-1 gene promoter and transcription initiation site in group I Burkitt lymphoma cell lines. PNAS 92:10565–69
    [Google Scholar]
  63. 63. 
    Babcock GJ, Hochberg D, Thorley-Lawson AD. 2000. The expression pattern of Epstein-Barr virus latent genes in vivo is dependent upon the differentiation stage of the infected B cell. Immunity 13:497–506
    [Google Scholar]
  64. 64. 
    Kempkes B, Robertson ES. 2015. Epstein-Barr virus latency: current and future perspectives. Curr. Opin. Virol. 14:138–44
    [Google Scholar]
  65. 65. 
    Yates JL, Warren N, Sugden B. 1985. Stable replication of plasmids derived from Epstein-Barr virus in various mammalian cells. Nature 313:812–15
    [Google Scholar]
  66. 66. 
    Mackey D, Sugden B. 1999. The linking regions of EBNA1 are essential for its support of replication and transcription. Mol. Cell. Biol. 19:3349–59
    [Google Scholar]
  67. 67. 
    Kang MS, Kieff E. 2015. Epstein-Barr virus latent genes. Exp. Mol. Med. 47:e131
    [Google Scholar]
  68. 68. 
    Woisetschlaeger M, Strominger JL, Speck SH 1989. Mutually exclusive use of viral promoters in Epstein-Barr virus latently infected lymphocytes. PNAS 86:6498–502
    [Google Scholar]
  69. 69. 
    Bell A, Skinner J, Kirby H, Rickinson A. 1998. Characterisation of regulatory sequences at the Epstein–Barr virus BamHI W promoter. Virology 252:149–61
    [Google Scholar]
  70. 70. 
    Tierney R, Kirby H, Nagra J, Rickinson A, Bell A. 2000. The Epstein-Barr virus promoter initiating B-cell transformation is activated by RFX proteins and the B-cell-specific activator protein BSAP/Pax5. J. Virol. 74:10458–67
    [Google Scholar]
  71. 71. 
    Tsai CN, Liu ST, Chang YS. 1995. Identification of a novel promoter located within the Bam HI Q region of the Epstein-Barr virus genome for the EBNA 1 gene. DNA Cell Biol 14:767–76
    [Google Scholar]
  72. 72. 
    Tao Q, Robertson KD, Manns A, Hildesheim A, Ambinder RF. 1998. The Epstein-Barr virus major latent promoter Qp is constitutively active, hypomethylated, and methylation sensitive. J. Virol. 72:7075–83
    [Google Scholar]
  73. 73. 
    Nonkwelo C, Ruf IK, Sample J. 1997. The Epstein-Barr virus EBNA-1 promoter Qp requires an initiator-like element. J. Virol. 71:354–61
    [Google Scholar]
  74. 74. 
    Nonkwelo C, Skinner J, Bell A, Rickinson A, Sample J. 1996. Transcription start sites downstream of the Epstein-Barr virus (EBV) Fp promoter in early-passage Burkitt lymphoma cells define a fourth promoter for expression of the EBV EBNA-1 protein. J. Virol. 70:623–27
    [Google Scholar]
  75. 75. 
    Sung NS, Wilson J, Davenport M, Sista ND, Pagano JS. 1994. Reciprocal regulation of the Epstein-Barr virus BamHI-F promoter by EBNA-1 and an E2F transcription factor. Mol. Cell. Biol. 14:7144–52
    [Google Scholar]
  76. 76. 
    Sung NS, Kenney S, Gutsch D, Pagano JS. 1991. EBNA-2 transactivates a lymphoid-specific enhancer in the BamHI C promoter of Epstein-Barr virus. J. Virol. 65:2164–69
    [Google Scholar]
  77. 77. 
    Rawlins DR, Milman G, Hayward SD, Hayward GS. 1985. Sequence-specific DNA binding of the Epstein-Barr virus nuclear antigen (EBNA-1) to clustered sites in the plasmid maintenance region. Cell 42:859–68
    [Google Scholar]
  78. 78. 
    Ceccarelli DF, Frappier L. 2000. Functional analyses of the EBNA1 origin DNA binding protein of Epstein-Barr virus. J. Virol. 74:4939–48
    [Google Scholar]
  79. 79. 
    Davenport MG, Pagano JS. 1999. Expression of EBNA-1 mRNA is regulated by cell cycle during Epstein-Barr virus type I latency. J. Virol. 73:3154–61
    [Google Scholar]
  80. 80. 
    Schaefer BC, Paulson E, Strominger JL, Speck SH. 1997. Constitutive activation of Epstein-Barr virus (EBV) nuclear antigen 1 gene transcription by IRF1 and IRF2 during restricted EBV latency. Mol. Cell. Biol. 17:873–86
    [Google Scholar]
  81. 81. 
    Zhang L, Pagano JS. 1999. Interferon regulatory factor 2 represses the Epstein-Barr virus BamHI Q latency promoter in type III latency. Mol. Cell. Biol. 19:3216–23
    [Google Scholar]
  82. 82. 
    Bertzbach LD, Conradie AM, You Y, Kaufer BB. 2020. Latest insights into Marek's disease virus pathogenesis and tumorigenesis. Cancers 12:647
    [Google Scholar]
  83. 83. 
    Strassheim S, Gennart I, Muylkens B, Andre M, Rasschaert D, Laurent S 2016. Oncogenic Marek's disease herpesvirus encodes an isoform of the conserved regulatory immediate early protein ICP27 generated by alternative promoter usage. J. Gen. Virol. 97:2399–410
    [Google Scholar]
  84. 84. 
    Rasschaert P, Gennart I, Boumart I, Dambrine G, Muylkens B et al. 2018. Specific transcriptional and post-transcriptional regulation of the major immediate early ICP4 gene of GaHV-2 during the lytic, latent and reactivation phases. J. Gen. Virol. 99:355–68
    [Google Scholar]
  85. 85. 
    Amor S, Strassheim S, Dambrine G, Remy S, Rasschaert D, Laurent S 2011. ICP27 protein of Marek's disease virus interacts with SR proteins and inhibits the splicing of cellular telomerase chTERT and viral vIL8 transcripts. J. Gen. Virol. 92:1273–78
    [Google Scholar]
  86. 86. 
    Gilden DH, Vafai A, Shtram Y, Becker Y, Devlin M, Wellish M. 1983. Varicella-zoster virus DNA in human sensory ganglia. Nature 306:478–80
    [Google Scholar]
  87. 87. 
    Mueller NH, Gilden DH, Cohrs RJ, Mahalingam R, Nagel MA. 2008. Varicella zoster virus infection: clinical features, molecular pathogenesis of disease, and latency. Neurol. Clin. 26:675–97
    [Google Scholar]
  88. 88. 
    Depledge DP, Ouwendijk WJD, Sadaoka T, Braspenning SE, Mori Y et al. 2018. A spliced latency-associated VZV transcript maps antisense to the viral transactivator gene 61. Nat. Commun. 9:1167
    [Google Scholar]
  89. 89. 
    Ouwendijk WJD, Depledge DP, Rajbhandari L, Lenac Rovis T, Jonjic S et al. 2020. Varicella-zoster virus VLT-ORF63 fusion transcript induces broad viral gene expression during reactivation from neuronal latency. Nat. Commun. 11:6324
    [Google Scholar]
  90. 90. 
    Nogalski MT, Collins-McMillen D, Yurochko AD. 2014. Overview of human cytomegalovirus pathogenesis. Methods Mol. Biol. 1119:15–28
    [Google Scholar]
  91. 91. 
    Britt WJ. 2018. Maternal immunity and the natural history of congenital human cytomegalovirus infection. Viruses 10:405
    [Google Scholar]
  92. 92. 
    Razonable RR, Hayden RT. 2013. Clinical utility of viral load in management of cytomegalovirus infection after solid organ transplantation. Clin. Microbiol. Rev. 26:703–27
    [Google Scholar]
  93. 93. 
    Stern-Ginossar N, Weisburd B, Michalski A, Le VT, Hein MY et al. 2012. Decoding human cytomegalovirus. Science 338:1088–93
    [Google Scholar]
  94. 94. 
    Parida M, Nilson KA, Li M, Ball CB, Fuchs HA et al. 2019. Nucleotide resolution comparison of transcription of human cytomegalovirus and host genomes reveals universal use of RNA polymerase II elongation control driven by dissimilar core promoter elements. mBio 10:e02047-18
    [Google Scholar]
  95. 95. 
    Leach FS, Mocarski ES. 1989. Regulation of cytomegalovirus late-gene expression: differential use of three start sites in the transcriptional activation of ICP36 gene expression. J. Virol. 63:1783–91
    [Google Scholar]
  96. 96. 
    Weiland KL, Oien NL, Homa F, Wathen MW. 1994. Functional analysis of human cytomegalovirus polymerase accessory protein. Virus Res 34:191–206
    [Google Scholar]
  97. 97. 
    Ripalti A, Boccuni MC, Campanini F, Landini MP. 1995. Cytomegalovirus-mediated induction of antisense mRNA expression to UL44 inhibits virus replication in an astrocytoma cell line: identification of an essential gene. J. Virol. 69:2047–57
    [Google Scholar]
  98. 98. 
    Isomura H, Stinski MF, Kudoh A, Nakayama S, Iwahori S et al. 2007. The late promoter of the human cytomegalovirus viral DNA polymerase processivity factor has an impact on delayed early and late viral gene products but not on viral DNA synthesis. J. Virol. 81:6197–206
    [Google Scholar]
  99. 99. 
    Isomura H, Stinski MF, Kudoh A, Murata T, Nakayama S et al. 2008. Noncanonical TATA sequence in the UL44 late promoter of human cytomegalovirus is required for the accumulation of late viral transcripts. J. Virol. 82:1638–46
    [Google Scholar]
  100. 100. 
    Isomura H, Stinski MF, Murata T, Yamashita Y, Kanda T et al. 2011. The human cytomegalovirus gene products essential for late viral gene expression assemble into prereplication complexes before viral DNA replication. J. Virol. 85:6629–44
    [Google Scholar]
  101. 101. 
    Perng YC, Campbell JA, Lenschow DJ, Yu D 2014. Human cytomegalovirus pUL79 is an elongation factor of RNA polymerase II for viral gene transcription. PLOS Pathog 10:e1004350
    [Google Scholar]
  102. 102. 
    Greaves RF, Mocarski ES. 1998. Defective growth correlates with reduced accumulation of a viral DNA replication protein after low-multiplicity infection by a human cytomegalovirus ie1 mutant. J. Virol. 72:366–79
    [Google Scholar]
  103. 103. 
    Sinclair JH, Baillie J, Bryant LA, Taylor-Wiedeman JA, Sissons JG. 1992. Repression of human cytomegalovirus major immediate early gene expression in a monocytic cell line. J. Gen. Virol. 73:Part 2433–35
    [Google Scholar]
  104. 104. 
    Goodrum F. 2016. Human cytomegalovirus latency: approaching the Gordian knot. Annu. Rev. Virol. 3:333–57
    [Google Scholar]
  105. 105. 
    Keller MJ, Wu AW, Andrews JI, McGonagill PW, Tibesar EE, Meier JL. 2007. Reversal of human cytomegalovirus major immediate-early enhancer/promoter silencing in quiescently infected cells via the cyclic AMP signaling pathway. J. Virol. 81:6669–81
    [Google Scholar]
  106. 106. 
    Yuan J, Liu X, Wu AW, McGonagill PW, Keller MJ et al. 2009. 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. 83:6391–403
    [Google Scholar]
  107. 107. 
    Liu X, Yuan J, Wu AW, McGonagill PW, Galle CS, Meier JL. 2010. Phorbol ester-induced human cytomegalovirus major immediate-early (MIE) enhancer activation through PKC-delta, CREB, and NF-κB desilences MIE gene expression in quiescently infected human pluripotent NTera2 cells. J. Virol. 84:8495–508
    [Google Scholar]
  108. 108. 
    Collins-McMillen D, Buehler J, Peppenelli M, Goodrum F. 2018. Molecular determinants and the regulation of human cytomegalovirus latency and reactivation. Viruses 10:44
    [Google Scholar]
  109. 109. 
    Boshart M, Weber F, Jahn G, Dorsch-Hasler K, Fleckenstein B, Schaffner W. 1985. A very strong enhancer is located upstream of an immediate early gene of human cytomegalovirus. Cell 41:521–30
    [Google Scholar]
  110. 110. 
    Wilkinson GW, Akrigg A. 1992. Constitutive and enhanced expression from the CMV major IE promoter in a defective adenovirus vector. Nucleic Acids Res 20:2233–39
    [Google Scholar]
  111. 111. 
    Thomsen DR, Stenberg RM, Goins WF, Stinski MF 1984. Promoter-regulatory region of the major immediate early gene of human cytomegalovirus. PNAS 81:659–63
    [Google Scholar]
  112. 112. 
    Sambucetti LC, Cherrington JM, Wilkinson GW, Mocarski ES. 1989. NF-κB activation of the cytomegalovirus enhancer is mediated by a viral transactivator and by T cell stimulation. EMBO J 8:4251–58
    [Google Scholar]
  113. 113. 
    Hunninghake GW, Monick MM, Liu B, Stinski MF. 1989. The promoter-regulatory region of the major immediate-early gene of human cytomegalovirus responds to T-lymphocyte stimulation and contains functional cyclic AMP-response elements. J. Virol. 63:3026–33
    [Google Scholar]
  114. 114. 
    Lang D, Fickenscher H, Stamminger T. 1992. Analysis of proteins binding to the proximal promoter region of the human cytomegalovirus IE-1/2 enhancer/promoter reveals both consensus and aberrant recognition sequences for transcription factors Sp1 and CREB. Nucleic Acids Res 20:3287–95
    [Google Scholar]
  115. 115. 
    Wade EJ, Klucher KM, Spector DH. 1992. An AP-1 binding site is the predominant cis-acting regulatory element in the 1.2-kilobase early RNA promoter of human cytomegalovirus. J. Virol. 66:2407–17
    [Google Scholar]
  116. 116. 
    Angulo A, Suto C, Heyman RA, Ghazal P. 1996. Characterization of the sequences of the human cytomegalovirus enhancer that mediate differential regulation by natural and synthetic retinoids. Mol. Endocrinol. 10:781–93
    [Google Scholar]
  117. 117. 
    Liu R, Baillie J, Sissons JG, Sinclair JH. 1994. The transcription factor YY1 binds to negative regulatory elements in the human cytomegalovirus major immediate early enhancer/promoter and mediates repression in non-permissive cells. Nucleic Acids Res 22:2453–59
    [Google Scholar]
  118. 118. 
    Pizzorno MC, Hayward GS. 1990. The IE2 gene products of human cytomegalovirus specifically down-regulate expression from the major immediate-early promoter through a target sequence located near the cap site. J. Virol. 64:6154–65
    [Google Scholar]
  119. 119. 
    Liu B, Hermiston TW, Stinski MF. 1991. A cis-acting element in the major immediate-early (IE) promoter of human cytomegalovirus is required for negative regulation by IE2. J. Virol. 65:897–903
    [Google Scholar]
  120. 120. 
    Kondo K, Xu J, Mocarski ES 1996. Human cytomegalovirus latent gene expression in granulocyte-macrophage progenitors in culture and in seropositive individuals. PNAS 93:11137–42
    [Google Scholar]
  121. 121. 
    Arend KC, Ziehr B, Vincent HA, Moorman NJ. 2016. Multiple transcripts encode full-length human cytomegalovirus IE1 and IE2 proteins during lytic infection. J. Virol. 90:8855–65
    [Google Scholar]
  122. 122. 
    Collins-McMillen D, Rak M, Buehler JC, Igarashi-Hayes S, Kamil JP et al. 2019. Alternative promoters drive human cytomegalovirus reactivation from latency. PNAS 116:17492–97
    [Google Scholar]
  123. 123. 
    Mao G, Marotta F, Yu J, Zhou L, Yu Y et al. 2008. DNA context and promoter activity affect gene expression in lentiviral vectors. Acta Biomed 79:192–96
    [Google Scholar]
  124. 124. 
    Wang R, Liang J, Jiang H, Qin LJ, Yang HT. 2008. Promoter-dependent EGFP expression during embryonic stem cell propagation and differentiation. Stem Cells Dev 17:279–89
    [Google Scholar]
  125. 125. 
    Mason R, Groves IJ, Wills MR, Sinclair JH, Reeves MB. 2020. Human cytomegalovirus major immediate early transcripts arise predominantly from the canonical major immediate early promoter in reactivating progenitor-derived dendritic cells. J. Gen. Virol. 101:635–44
    [Google Scholar]
  126. 126. 
    Ibanez CE, Schrier R, Ghazal P, Wiley C, Nelson JA. 1991. Human cytomegalovirus productively infects primary differentiated macrophages. J. Virol. 65:6581–88
    [Google Scholar]
  127. 127. 
    Miyamoto K, Araki KY, Naka K, Arai F, Takubo K et al. 2007. Foxo3a is essential for maintenance of the hematopoietic stem cell pool. Cell Stem Cell 1:101–12
    [Google Scholar]
  128. 128. 
    Zheng QF, Wang HM, Wang ZF, Liu JY, Zhang Q et al. 2017. Reprogramming of histone methylation controls the differentiation of monocytes into macrophages. FEBS J 284:1309–23
    [Google Scholar]
  129. 129. 
    Buehler J, Zeltzer S, Reitsma J, Petrucelli A, Umashankar M et al. 2016. Opposing regulation of the EGF receptor: a molecular switch controlling cytomegalovirus latency and replication. PLOS Pathog 12:e1005655
    [Google Scholar]
  130. 130. 
    Hale AE, Collins-McMillen D, Lenarcic EM, Igarashi S, Kamil JP et al. 2020. FOXO transcription factors activate alternative major immediate early promoters to induce human cytomegalovirus reactivation. PNAS 117:18764–70
    [Google Scholar]
  131. 131. 
    Krishna BA, Wass AB, O'Connor CM 2020. Activator protein-1 transactivation of the major immediate early locus is a determinant of cytomegalovirus reactivation from latency. PNAS 117:20860–67
    [Google Scholar]
  132. 132. 
    Bertzbach LD, Pfaff F, Pauker VI, Kheimar AM, Hoper D et al. 2019. The transcriptional landscape of Marek's disease virus in primary chicken B cells reveals novel splice variants and genes. Viruses 11:264
    [Google Scholar]
  133. 133. 
    O'Grady T, Feswick A, Hoffman BA, Wang Y, Medina EM et al. 2019. Genome-wide transcript structure resolution reveals abundant alternate isoform usage from murine gammaherpesvirus 68. Cell Rep 27:3988–4002.e5
    [Google Scholar]
  134. 134. 
    Djavadian R, Hayes M, Johannsen E. 2018. CAGE-seq analysis of Epstein-Barr virus lytic gene transcription: 3 kinetic classes from 2 mechanisms. PLOS Pathog 14:e1007114
    [Google Scholar]
  135. 135. 
    Erhard F, Halenius A, Zimmermann C, L'Hernault A, Kowalewski DJ et al. 2018. Improved Ribo-seq enables identification of cryptic translation events. Nat. Methods 15:363–66
    [Google Scholar]
  136. 136. 
    Arias C, Weisburd B, Stern-Ginossar N, Mercier A, Madrid AS et al. 2014. KSHV 2.0: a comprehensive annotation of the Kaposi's sarcoma-associated herpesvirus genome using next-generation sequencing reveals novel genomic and functional features. PLOS Pathog 10:e1003847
    [Google Scholar]
  137. 137. 
    Whisnant AW, Jurges CS, Hennig T, Wyler E, Prusty B et al. 2020. Integrative functional genomics decodes herpes simplex virus 1. Nat. Commun. 11:2038
    [Google Scholar]
  138. 138. 
    Depledge DP, Srinivas KP, Sadaoka T, Bready D, Mori Y et al. 2019. Direct RNA sequencing on nanopore arrays redefines the transcriptional complexity of a viral pathogen. Nat. Commun. 10:754
    [Google Scholar]
  139. 139. 
    Braspenning SE, Sadaoka T, Breuer J, Verjans G, Ouwendijk WJD, Depledge DP. 2020. Decoding the architecture of the varicella-zoster virus transcriptome. mBio 11:e01568-20
    [Google Scholar]
  140. 140. 
    Aubry V, Mure F, Mariame B, Deschamps T, Wyrwicz LS et al. 2014. Epstein-Barr virus late gene transcription depends on the assembly of a virus-specific preinitiation complex. J. Virol. 88:12825–38
    [Google Scholar]
  141. 141. 
    Chapa TJ, Perng YC, French AR, Yu D 2014. Murine cytomegalovirus protein pM92 is a conserved regulator of viral late gene expression. J. Virol. 88:131–42
    [Google Scholar]
  142. 142. 
    Gruffat H, Kadjouf F, Mariame B, Manet E. 2012. The Epstein-Barr virus BcRF1 gene product is a TBP-like protein with an essential role in late gene expression. J. Virol. 86:6023–32
    [Google Scholar]
  143. 143. 
    Omoto S, Mocarski ES. 2013. Cytomegalovirus UL91 is essential for transcription of viral true late (γ2) genes. J. Virol. 87:8651–64
    [Google Scholar]
  144. 144. 
    Weekes MP, Tomasec P, Huttlin EL, Fielding CA, Nusinow D et al. 2014. Quantitative temporal viromics: an approach to investigate host-pathogen interaction. Cell 157:1460–72
    [Google Scholar]
  145. 145. 
    Price AM, Luftig MA. 2014. Dynamic Epstein-Barr virus gene expression on the path to B-cell transformation. Adv. Virus Res. 88:279–313
    [Google Scholar]
  146. 146. 
    Gu W, Lee HC, Chaves D, Youngman EM, Pazour GJ et al. 2012. CapSeq and CIP-TAP identify Pol II start sites and reveal capped small RNAs as C. elegans piRNA precursors. Cell 151:1488–500
    [Google Scholar]
  147. 147. 
    Murata M, Nishiyori-Sueki H, Kojima-Ishiyama M, Carninci P, Hayashizaki Y, Itoh M. 2014. Detecting expressed genes using CAGE. Methods Mol. Biol. 1164:67–85
    [Google Scholar]
  148. 148. 
    Tan K, Wong KH. 2019. RNA polymerase II ChIP-seq—a powerful and highly affordable method for studying fungal genomics and physiology. Biophys. Rev. 11:79–82
    [Google Scholar]
  149. 149. 
    Hinnebusch AG, Ivanov IP, Sonenberg N. 2016. Translational control by 5′-untranslated regions of eukaryotic mRNAs. Science 352:1413–16
    [Google Scholar]
  150. 150. 
    Pyhtila B, Zheng T, Lager PJ, Keene JD, Reedy MC, Nicchitta CV. 2008. Signal sequence- and translation-independent mRNA localization to the endoplasmic reticulum. RNA 14:445–53
    [Google Scholar]
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