1932

Abstract

Persistent viral infections require a host cell reservoir that maintains functional copies of the viral genome. To this end, several DNA viruses maintain their genomes as extrachromosomal DNA minichromosomes in actively dividing cells. These viruses typically encode a viral protein that binds specifically to viral DNA genomes and tethers them to host mitotic chromosomes, thus enabling the viral genomes to hitchhike or piggyback into daughter cells. Viruses that use this tethering mechanism include papillomaviruses and the gammaherpesviruses Epstein-Barr virus and Kaposi's sarcoma-associated herpesvirus. This review describes the advantages and consequences of persistent extrachromosomal viral genome replication.

Associated Article

There are media items related to this article:
Hitchhiking of Viral Genomes on Cellular Chromosomes: Video 1
Loading

Article metrics loading...

/content/journals/10.1146/annurev-virology-092818-015716
2019-09-29
2024-04-18
Loading full text...

Full text loading...

/deliver/fulltext/virology/6/1/annurev-virology-092818-015716.html?itemId=/content/journals/10.1146/annurev-virology-092818-015716&mimeType=html&fmt=ahah

Literature Cited

  1. 1. 
    Van Doorslaer K. 2013. Evolution of the papillomaviridae. Virology 445:11–20
    [Google Scholar]
  2. 2. 
    Mariggio G, Koch S, Schulz TF 2017. Kaposi sarcoma herpesvirus pathogenesis. Philos. Trans. R. Soc. B Biol. Sci. 372:20160275
    [Google Scholar]
  3. 3. 
    Stanley MA. 2012. Epithelial cell responses to infection with human papillomavirus. Clin. Microbiol. Rev. 25:215–22
    [Google Scholar]
  4. 4. 
    Van Doorslaer K, Li Z, Xirasagar S, Maes P, Kaminsky D et al. 2017. The Papillomavirus Episteme: a major update to the papillomavirus sequence database. Nucleic Acids Res 45:D499–506
    [Google Scholar]
  5. 5. 
    McBride AA. 2017. Oncogenic human papillomaviruses. Philos. Trans. R. Soc. B Biol. Sci. 372:20160273
    [Google Scholar]
  6. 6. 
    Thorley-Lawson DA. 2015. EBV persistence—introducing the virus. Curr. Top. Microbiol. Immunol. 390:151–209
    [Google Scholar]
  7. 7. 
    Zimmermann J, Hammerschmidt W. 1995. Structure and role of the terminal repeats of Epstein-Barr virus in processing and packaging of virion DNA. J. Virol. 69:3147–55
    [Google Scholar]
  8. 8. 
    Kranjec C, Doorbar J. 2016. Human papillomavirus infection and induction of neoplasia: a matter of fitness. Curr. Opin. Virol. 20:129–36
    [Google Scholar]
  9. 9. 
    Nanbo A, Sugden A, Sugden B 2007. The coupling of synthesis and partitioning of EBV's plasmid replicon is revealed in live cells. EMBO J 26:4252–62
    [Google Scholar]
  10. 10. 
    Chiu YF, Sugden AU, Fox K, Hayes M, Sugden B 2017. Kaposi's sarcoma-associated herpesvirus stably clusters its genomes across generations to maintain itself extrachromosomally. J. Cell Biol. 216:2745–58
    [Google Scholar]
  11. 11. 
    Ustav M, Stenlund A. 1991. Transient replication of BPV-1 requires two viral polypeptides encoded by the E1 and E2 open reading frames. EMBO J 10:449–57
    [Google Scholar]
  12. 12. 
    Ustav M, Ustav E, Szymanski P, Stenlund A 1991. Identification of the origin of replication of bovine papillomavirus and characterization of the viral origin recognition factor E1. EMBO J 10:4321–29
    [Google Scholar]
  13. 13. 
    Mohr IJ, Clark R, Sun S, Androphy EJ, MacPherson P, Botchan MR 1990. Targeting the E1 replication protein to the papillomavirus origin of replication by complex formation with the E2 transactivator. Science 250:1694–99
    [Google Scholar]
  14. 14. 
    Sanders CM, Stenlund A. 1998. Recruitment and loading of the E1 initiator protein: an ATP-dependent process catalysed by a transcription factor. EMBO J 17:7044–55
    [Google Scholar]
  15. 15. 
    DiGiuseppe S, Luszczek W, Keiffer TR, Bienkowska-Haba M, Guion LG, Sapp MJ 2016. Incoming human papillomavirus type 16 genome resides in a vesicular compartment throughout mitosis. PNAS 113:6289–94
    [Google Scholar]
  16. 16. 
    Aydin I, Villalonga-Planells R, Greune L, Bronnimann MP, Calton CM et al. 2017. A central region in the minor capsid protein of papillomaviruses facilitates viral genome tethering and membrane penetration for mitotic nuclear entry. PLOS Pathog 13:e1006308
    [Google Scholar]
  17. 17. 
    McBride AA. 2017. Mechanisms and strategies of papillomavirus replication. Biol. Chem. 398:919–27
    [Google Scholar]
  18. 18. 
    Jang MK, Kwon D, McBride AA 2009. Papillomavirus E2 proteins and the host BRD4 protein associate with transcriptionally active cellular chromatin. J. Virol. 83:2592–600
    [Google Scholar]
  19. 19. 
    Skiadopoulos MH, McBride AA. 1998. Bovine papillomavirus type 1 genomes and the E2 transactivator protein are closely associated with mitotic chromatin. J. Virol. 72:2079–88
    [Google Scholar]
  20. 20. 
    Piirsoo M, Ustav E, Mandel T, Stenlund A, Ustav M 1996. Cis and trans requirements for stable episomal maintenance of the BPV-1 replicator. EMBO J 15:1–11
    [Google Scholar]
  21. 21. 
    Kim K, Lambert PF. 2002. E1 protein of bovine papillomavirus 1 is not required for the maintenance of viral plasmid DNA replication. Virology 293:10–14
    [Google Scholar]
  22. 22. 
    Egawa N, Nakahara T, Ohno S, Narisawa-Saito M, Yugawa T et al. 2012. The E1 protein of human papillomavirus type 16 is dispensable for maintenance replication of the viral genome. J. Virol. 86:3276–83
    [Google Scholar]
  23. 23. 
    Fradet-Turcotte A, Bergeron-Labrecque F, Moody CA, Lehoux M, Laimins LA, Archambault J 2011. Nuclear accumulation of the papillomavirus E1 helicase blocks S-phase progression and triggers an ATM-dependent DNA damage response. J. Virol. 85:8996–9012
    [Google Scholar]
  24. 24. 
    Fradet-Turcotte A, Moody C, Laimins LA, Archambault J 2010. Nuclear export of human papillomavirus type 31 E1 is regulated by Cdk2 phosphorylation and required for viral genome maintenance. J. Virol. 84:11747–60
    [Google Scholar]
  25. 25. 
    Sakakibara N, Mitra R, McBride AA 2011. The papillomavirus E1 helicase activates a cellular DNA damage response in viral replication foci. J. Virol. 85:8981–95
    [Google Scholar]
  26. 26. 
    Gilbert DM, Cohen SN. 1987. Bovine papilloma virus plasmids replicate randomly in mouse fibroblasts throughout S phase of the cell cycle. Cell 50:59–68
    [Google Scholar]
  27. 27. 
    Hoffmann R, Hirt B, Bechtold V, Beard P, Raj K 2006. Different modes of human papillomavirus DNA replication during maintenance. J. Virol. 80:4431–39
    [Google Scholar]
  28. 28. 
    Moody CA, Laimins LA. 2009. Human papillomaviruses activate the ATM DNA damage pathway for viral genome amplification upon differentiation. PLOS Pathog 5:e1000605
    [Google Scholar]
  29. 29. 
    Sakakibara N, Chen D, McBride AA 2013. Papillomaviruses use recombination-dependent replication to vegetatively amplify their genomes in differentiated cells. PLOS Pathog 9:e1003321
    [Google Scholar]
  30. 30. 
    Leight ER, Sugden B. 2001. Establishment of an oriP replicon is dependent upon an infrequent, epigenetic event. Mol. Cell. Biol. 21:4149–61
    [Google Scholar]
  31. 31. 
    Yates JL, Guan N. 1991. Epstein-Barr virus-derived plasmids replicate only once per cell cycle and are not amplified after entry into cells. J. Virol. 65:483–88
    [Google Scholar]
  32. 32. 
    Yates J, Warren N, Reisman D, Sugden B 1984. A cis-acting element from the Epstein-Barr viral genome that permits stable replication of recombinant plasmids in latently infected cells. PNAS 81:3806–10
    [Google Scholar]
  33. 33. 
    Kanda T, Kamiya M, Maruo S, Iwakiri D, Takada K 2007. Symmetrical localization of extrachromosomally replicating viral genomes on sister chromatids. J. Cell Sci. 120:1529–39
    [Google Scholar]
  34. 34. 
    Chiu YF, Sugden B. 2018. Plasmid partitioning by human tumor viruses. J. Virol. 92:e02170–17
    [Google Scholar]
  35. 35. 
    Weitzman MD, Fradet-Turcotte A. 2018. Virus DNA replication and the host DNA damage response. Annu. Rev. Virol. 5:141–64
    [Google Scholar]
  36. 36. 
    Ballestas ME, Chatis PA, Kaye KM 1999. Efficient persistence of extrachromosomal KSHV DNA mediated by latency-associated nuclear antigen. Science 284:641–44
    [Google Scholar]
  37. 37. 
    Stedman W, Deng Z, Lu F, Lieberman PM 2004. ORC, MCM, and histone hyperacetylation at the Kaposi's sarcoma-associated herpesvirus latent replication origin. J. Virol. 78:12566–75
    [Google Scholar]
  38. 38. 
    Juillard F, Tan M, Li S, Kaye KM 2016. Kaposi's sarcoma herpesvirus genome persistence. Front. Microbiol. 7:1149
    [Google Scholar]
  39. 39. 
    McBride AA. 2013. The papillomavirus E2 proteins. Virology 445:57–79
    [Google Scholar]
  40. 40. 
    Hegde RS, Grossman SR, Laimins LA, Sigler PB 1992. Crystal structure at 1.7 Å of the bovine papillomavirus-1 E2 DNA-binding domain bound to its DNA target. Nature 359:505–12
    [Google Scholar]
  41. 41. 
    Bochkarev A, Barwell JA, Pfuetzner RA, Furey W Jr. Edwards AM, Frappier L 1995. Crystal structure of the DNA-binding domain of the Epstein-Barr virus origin-binding protein EBNA 1. Cell 83:39–46
    [Google Scholar]
  42. 42. 
    Hellert J, Weidner-Glunde M, Krausze J, Lunsdorf H, Ritter C et al. 2015. The 3D structure of Kaposi sarcoma herpesvirus LANA C-terminal domain bound to DNA. PNAS 112:6694–99
    [Google Scholar]
  43. 43. 
    Shire K, Ceccarelli DFJ, Avolio-Hunter TM, Frappier L 1999. EBP2, a human protein that interacts with sequences of the Epstein-Barr virus nuclear antigen 1 important for plasmid maintenance. J. Virol. 73:2587–95
    [Google Scholar]
  44. 44. 
    Marechal V, Dehee A, Chikhi-Brachet R, Piolot T, Coppey-Moisan M, Nicolas JC 1999. Mapping EBNA-1 domains involved in binding to metaphase chromosomes. J. Virol. 73:4385–92
    [Google Scholar]
  45. 45. 
    Sears J, Ujihara M, Wong S, Ott C, Middeldorp J, Aiyar A 2004. 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. 78:11487–505
    [Google Scholar]
  46. 46. 
    Kapoor P, Lavoie BD, Frappier L 2005. EBP2 plays a key role in Epstein-Barr virus mitotic segregation and is regulated by aurora family kinases. Mol. Cell. Biol. 25:4934–45
    [Google Scholar]
  47. 47. 
    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]
  48. 48. 
    Nayyar VK, Shire K, Frappier L 2009. Mitotic chromosome interactions of Epstein-Barr nuclear antigen 1 (EBNA1) and human EBNA1-binding protein 2 (EBP2). J. Cell Sci. 122:4341–50
    [Google Scholar]
  49. 49. 
    Bochkarev A, Barwell JA, Pfuetzner RA, Bochkareva E, Frappier L, Edwards AM 1996. Crystal structure of the DNA-binding domain of the Epstein-Barr virus origin-binding protein, EBNA1, bound to DNA. Cell 84:791–800
    [Google Scholar]
  50. 50. 
    Cruickshank J, Shire K, Davidson AR, Edwards AM, Frappier L 2000. Two domains of the Epstein-Barr virus origin DNA-binding protein, EBNA1, orchestrate sequence-specific DNA binding. J. Biol. Chem. 275:22273–77
    [Google Scholar]
  51. 51. 
    Murat P, Zhong J, Lekieffre L, Cowieson NP, Clancy JL et al. 2014. G-quadruplexes regulate Epstein-Barr virus-encoded nuclear antigen 1 mRNA translation. Nat. Chem. Biol. 10:358–64
    [Google Scholar]
  52. 52. 
    Barbera AJ, Chodaparambil JV, Kelley-Clarke B, Joukov V, Walter JC et al. 2006. The nucleosomal surface as a docking station for Kaposi's sarcoma herpesvirus LANA. Science 311:856–61
    [Google Scholar]
  53. 53. 
    Wong LY, Matchett GA, Wilson AC 2004. Transcriptional activation by the Kaposi's sarcoma-associated herpesvirus latency-associated nuclear antigen is facilitated by an N-terminal chromatin-binding motif. J. Virol. 78:10074–85
    [Google Scholar]
  54. 54. 
    Barbera AJ, Ballestas ME, Kaye KM 2004. The Kaposi's sarcoma-associated herpesvirus latency-associated nuclear antigen 1 N terminus is essential for chromosome association, DNA replication, and episome persistence. J. Virol. 78:294–301
    [Google Scholar]
  55. 55. 
    Piolot T, Tramier M, Coppey M, Nicolas JC, Marechal V 2001. Close but distinct regions of human herpesvirus 8 latency-associated nuclear antigen 1 are responsible for nuclear targeting and binding to human mitotic chromosomes. J. Virol. 75:3948–59
    [Google Scholar]
  56. 56. 
    Correia B, Cerqueira SA, Beauchemin C, Pires de Miranda M, Li S et al. 2013. Crystal structure of the gamma-2 herpesvirus LANA DNA binding domain identifies charged surface residues which impact viral latency. PLOS Pathog 9:e1003673
    [Google Scholar]
  57. 57. 
    Domsic JF, Chen HS, Lu F, Marmorstein R, Lieberman PM 2013. Molecular basis for oligomeric-DNA binding and episome maintenance by KSHV LANA. PLOS Pathog 9:e1003672
    [Google Scholar]
  58. 58. 
    Hellert J, Weidner-Glunde M, Krausze J, Richter U, Adler H et al. 2013. A structural basis for BRD2/4-mediated host chromatin interaction and oligomer assembly of Kaposi sarcoma-associated herpesvirus and murine gammaherpesvirus LANA proteins. PLOS Pathog 9:e1003640
    [Google Scholar]
  59. 59. 
    Li S, Tan M, Juillard F, Ponnusamy R, Correia B et al. 2015. The Kaposi sarcoma herpesvirus latency-associated nuclear antigen DNA binding domain dorsal positive electrostatic patch facilitates DNA replication and episome persistence. J. Biol. Chem. 290:28084–96
    [Google Scholar]
  60. 60. 
    Krithivas A, Fujimuro M, Weidner M, Young DB, Hayward SD 2002. Protein interactions targeting the latency-associated nuclear antigen of Kaposi's sarcoma-associated herpesvirus to cell chromosomes. J. Virol. 76:11596–604
    [Google Scholar]
  61. 61. 
    Kelley-Clarke B, Ballestas ME, Komatsu T, Kaye KM 2007. Kaposi's sarcoma herpesvirus C-terminal LANA concentrates at pericentromeric and peri-telomeric regions of a subset of mitotic chromosomes. Virology 357:149–57
    [Google Scholar]
  62. 62. 
    Kelley-Clarke B, Ballestas ME, Srinivasan V, Barbera AJ, Komatsu T et al. 2007. Determination of Kaposi's sarcoma-associated herpesvirus C-terminal latency-associated nuclear antigen residues mediating chromosome association and DNA binding. J. Virol. 81:4348–56
    [Google Scholar]
  63. 63. 
    Zaldumbide A, Ossevoort M, Wiertz EJ, Hoeben RC 2007. In cis inhibition of antigen processing by the latency-associated nuclear antigen I of Kaposi sarcoma herpes virus. Mol. Immunol. 44:1352–60
    [Google Scholar]
  64. 64. 
    Androphy EJ, Lowy DR, Schiller JT 1987. Bovine papillomavirus E2 trans-activating gene product binds to specific sites in papillomavirus DNA. Nature 325:70–73
    [Google Scholar]
  65. 65. 
    Li R, Knight J, Bream G, Stenlund A, Botchan M 1989. Specific recognition nucleotides and their DNA context determine the affinity of E2 protein for 17 binding sites in the BPV-1 genome. Genes Dev 3:510–26
    [Google Scholar]
  66. 66. 
    Van Doorslaer K, Chen D, Chapman S, Khan J, McBride AA 2017. Persistence of an oncogenic papillomavirus genome requires cis elements from the viral transcriptional enhancer. mBio 8:e01758–17
    [Google Scholar]
  67. 67. 
    Ustav M Jr., Castaneda FR, Reinson T, Mannik A, Ustav M. 2015. Human papillomavirus type 18 cis-elements crucial for segregation and latency. PLOS ONE 10:e0135770
    [Google Scholar]
  68. 68. 
    O'Connor M, Chan SY, Bernard HU 1995. Transcription factor binding sites in the long control region of genital HPVs. Human PapillomavirusesIII21–40 Los Alamos, NM: Los Alamos Natl. Lab.
    [Google Scholar]
  69. 69. 
    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]
  70. 70. 
    Reisman D, Yates J, Sugden B 1985. A putative origin of replication of plasmids derived from Epstein-Barr virus is composed of two cis-acting components. Mol. Cell. Biol. 5:1822–32
    [Google Scholar]
  71. 71. 
    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]
  72. 72. 
    Norio P, Schildkraut CL, Yates JL 2000. Initiation of DNA replication within oriP is dispensable for stable replication of the latent Epstein-Barr virus chromosome after infection of established cell lines. J. Virol. 74:8563–74
    [Google Scholar]
  73. 73. 
    Ott E, Norio P, Ritzi M, Schildkraut C, Schepers A 2011. The dyad symmetry element of Epstein-Barr virus is a dominant but dispensable replication origin. PLOS ONE 6:e18609
    [Google Scholar]
  74. 74. 
    Lupton S, Levine AJ. 1985. Mapping genetic elements of Epstein-Barr virus that facilitate extrachromosomal persistence of Epstein-Barr virus-derived plasmids in human cells. Mol. Cell. Biol. 5:2533–42
    [Google Scholar]
  75. 75. 
    Harrison S, Fisenne K, Hearing J 1994. Sequence requirements of the Epstein-Barr virus latent origin of DNA replication. J. Virol. 68:1913–25
    [Google Scholar]
  76. 76. 
    Wysokenski DA, Yates JL. 1989. Multiple EBNA1-binding sites are required to form an EBNA1-dependent enhancer and to activate a minimal replicative origin within oriP of Epstein-Barr virus. J. Virol. 63:2657–66
    [Google Scholar]
  77. 77. 
    Garber AC, Hu J, Renne R 2002. Latency-associated nuclear antigen (LANA) cooperatively binds to two sites within the terminal repeat, and both sites contribute to the ability of LANA to suppress transcription and to facilitate DNA replication. J. Biol. Chem. 277:27401–11
    [Google Scholar]
  78. 78. 
    Komatsu T, Ballestas ME, Barbera AJ, Kelley-Clarke B, Kaye KM 2004. KSHV LANA1 binds DNA as an oligomer and residues N-terminal to the oligomerization domain are essential for DNA binding, replication, and episome persistence. Virology 319:225–36
    [Google Scholar]
  79. 79. 
    Hu J, Renne R. 2005. Characterization of the minimal replicator of Kaposi's sarcoma-associated herpesvirus latent origin. J. Virol. 79:2637–42
    [Google Scholar]
  80. 80. 
    Dey A, Chitsaz F, Abbasi A, Misteli T, Ozato K 2003. The double bromodomain protein Brd4 binds to acetylated chromatin during interphase and mitosis. PNAS 100:8758–63
    [Google Scholar]
  81. 81. 
    Jang MK, Mochizuki K, Zhou M, Jeong HS, Brady JN, Ozato K 2005. The bromodomain protein Brd4 is a positive regulatory component of P-TEFb and stimulates RNA polymerase II-dependent transcription. Mol. Cell 19:523–34
    [Google Scholar]
  82. 82. 
    You J, Croyle JL, Nishimura A, Ozato K, Howley PM 2004. Interaction of the bovine papillomavirus E2 protein with Brd4 tethers the viral DNA to host mitotic chromosomes. Cell 117:349–60
    [Google Scholar]
  83. 83. 
    Baxter MK, McPhillips MG, Ozato K, McBride AA 2005. The mitotic chromosome binding activity of the papillomavirus E2 protein correlates with interaction with the cellular chromosomal protein, Brd4. J. Virol. 79:4806–18
    [Google Scholar]
  84. 84. 
    McPhillips MG, Ozato K, McBride AA 2005. Interaction of bovine papillomavirus E2 protein with Brd4 stabilizes its association with chromatin. J. Virol. 79:8920–32
    [Google Scholar]
  85. 85. 
    Oliveira JG, Colf LA, McBride AA 2006. Variations in the association of papillomavirus E2 proteins with mitotic chromosomes. PNAS 103:1047–52
    [Google Scholar]
  86. 86. 
    Abbate EA, Voitenleitner C, Botchan MR 2006. Structure of the papillomavirus DNA-tethering complex E2:Brd4 and a peptide that ablates HPV chromosomal association. Mol. Cell 24:877–89
    [Google Scholar]
  87. 87. 
    Donaldson MM, Boner W, Morgan IM 2007. TopBP1 regulates human papillomavirus type 16 E2 interaction with chromatin. J. Virol. 81:4338–42
    [Google Scholar]
  88. 88. 
    Sakakibara N, Chen D, Jang MK, Kang DW, Luecke HF et al. 2013. Brd4 is displaced from HPV replication factories as they expand and amplify viral DNA. PLOS Pathog 9:e1003777
    [Google Scholar]
  89. 89. 
    Wang X, Helfer CM, Pancholi N, Bradner JE, You J 2013. Recruitment of Brd4 to the human papillomavirus type 16 DNA replication complex is essential for replication of viral DNA. J. Virol. 87:3871–84
    [Google Scholar]
  90. 90. 
    Gauson EJ, Donaldson MM, Dornan ES, Wang X, Bristol M et al. 2015. Evidence supporting a role for TopBP1 and Brd4 in the initiation but not continuation of human papillomavirus 16 E1/E2-mediated DNA replication. J. Virol. 89:4980–91
    [Google Scholar]
  91. 91. 
    Stubenrauch F, Lim HB, Laimins LA 1998. Differential requirements for conserved E2 binding sites in the life cycle of oncogenic human papillomavirus type 31. J. Virol. 72:1071–77
    [Google Scholar]
  92. 92. 
    Mehta K, Laimins L. 2018. Human papillomaviruses preferentially recruit DNA repair factors to viral genomes for rapid repair and amplification. mBio 9:e00064–18
    [Google Scholar]
  93. 93. 
    Bentley P, Tan MJA, McBride AA, White EA, Howley PM 2018. The SMC5/6 complex interacts with the papillomavirus E2 protein and influences maintenance of viral episomal DNA. J. Virol. 92:e00356–18
    [Google Scholar]
  94. 94. 
    Samora CP, Saksouk J, Goswami P, Wade BO, Singleton MR et al. 2016. Ctf4 links DNA replication with sister chromatid cohesion establishment by recruiting the Chl1 helicase to the replisome. Mol. Cell 63:371–84
    [Google Scholar]
  95. 95. 
    Harris L, McFarlane-Majeed L, Campos-Leon K, Roberts S, Parish JL 2017. The cellular DNA helicase ChlR1 regulates chromatin and nuclear matrix attachment of the human papillomavirus 16 E2 protein and high-copy-number viral genome establishment. J. Virol. 91:e01853–16
    [Google Scholar]
  96. 96. 
    Van Tine BA, Dao LD, Wu SY, Sonbuchner TM, Lin BY et al. 2004. Human papillomavirus (HPV) origin-binding protein associates with mitotic spindles to enable viral DNA partitioning. PNAS 101:4030–35
    [Google Scholar]
  97. 97. 
    Tan CL, Teissier S, Gunaratne J, Quek LS, Bellanger S 2015. Stranglehold on the spindle assembly checkpoint: The human papillomavirus E2 protein provokes BUBR1-dependent aneuploidy. Cell Cycle 14:1459–70
    [Google Scholar]
  98. 98. 
    Yu T, Peng YC, Androphy EJ 2007. Mitotic kinesin-like protein 2 binds and colocalizes with papillomavirus E2 during mitosis. J. Virol. 81:1736–45
    [Google Scholar]
  99. 99. 
    Chakravorty A, Sugden B. 2015. The AT-hook DNA binding ability of the Epstein Barr virus EBNA1 protein is necessary for the maintenance of viral genomes in latently infected cells. Virology 484:251–58
    [Google Scholar]
  100. 100. 
    Sears J, Kolman J, Wahl GM, Aiyar A 2003. Metaphase chromosome tethering is necessary for the DNA synthesis and maintenance of oriP plasmids but is insufficient for transcription activation by Epstein-Barr nuclear antigen 1. J. Virol. 77:11767–80
    [Google Scholar]
  101. 101. 
    Hung SC, Kang MS, Kieff E 2001. Maintenance of Epstein-Barr virus (EBV) oriP-based episomes requires EBV-encoded nuclear antigen-1 chromosome-binding domains, which can be replaced by high-mobility group-I or histone H1. PNAS 98:1865–70
    [Google Scholar]
  102. 102. 
    Lin A, Wang S, Nguyen T, Shire K, Frappier L 2008. The EBNA1 protein of Epstein-Barr virus functionally interacts with Brd4. J. Virol. 82:12009–19
    [Google Scholar]
  103. 103. 
    Norseen J, Thomae A, Sridharan V, Aiyar A, Schepers A, Lieberman PM 2008. RNA-dependent recruitment of the origin recognition complex. EMBO J 27:3024–35
    [Google Scholar]
  104. 104. 
    Norseen J, Johnson FB, Lieberman PM 2009. Role for G-quadruplex RNA binding by Epstein-Barr virus nuclear antigen 1 in DNA replication and metaphase chromosome attachment. J. Virol. 83:10336–46
    [Google Scholar]
  105. 105. 
    Deschamps T, Bazot Q, Leske DM, MacLeod R, Mompelat D et al. 2017. Epstein-Barr virus nuclear antigen 1 interacts with regulator of chromosome condensation 1 dynamically throughout the cell cycle. J. Gen. Virol. 98:251–65
    [Google Scholar]
  106. 106. 
    Matsumura S, Persson LM, Wong L, Wilson AC 2010. The latency-associated nuclear antigen interacts with MeCP2 and nucleosomes through separate domains. J. Virol. 84:2318–30
    [Google Scholar]
  107. 107. 
    Si H, Verma SC, Lampson MA, Cai Q, Robertson ES 2008. Kaposi's sarcoma-associated herpesvirus-encoded LANA can interact with the nuclear mitotic apparatus protein to regulate genome maintenance and segregation. J. Virol. 82:6734–46
    [Google Scholar]
  108. 108. 
    Xiao B, Verma SC, Cai Q, Kaul R, Lu J et al. 2010. Bub1 and CENP-F can contribute to Kaposi's sarcoma-associated herpesvirus genome persistence by targeting LANA to kinetochores. J. Virol. 84:9718–32
    [Google Scholar]
  109. 109. 
    You J, Srinivasan V, Denis GV, Harrington WJ Jr., Ballestas ME et al. 2006. Kaposi's sarcoma-associated herpesvirus latency-associated nuclear antigen interacts with bromodomain protein Brd4 on host mitotic chromosomes. J. Virol. 80:8909–19
    [Google Scholar]
  110. 110. 
    Sekhar V, Reed SC, McBride AA 2010. Interaction of the betapapillomavirus E2 tethering protein with mitotic chromosomes. J. Virol. 84:543–57
    [Google Scholar]
  111. 111. 
    McPhillips MG, Oliveira JG, Spindler JE, Mitra R, McBride AA 2006. Brd4 is required for e2-mediated transcriptional activation but not genome partitioning of all papillomaviruses. J. Virol. 80:9530–43
    [Google Scholar]
  112. 112. 
    Hu J, Yang Y, Turner PC, Jain V, McIntyre LM, Renne R 2014. LANA binds to multiple active viral and cellular promoters and associates with the H3K4methyltransferase hSET1 complex. PLOS Pathog 10:e1004240
    [Google Scholar]
  113. 113. 
    Mercier A, Arias C, Madrid AS, Holdorf MM, Ganem D 2014. Site-specific association with host and viral chromatin by Kaposi's sarcoma-associated herpesvirus LANA and its reversal during lytic reactivation. J. Virol. 88:6762–77
    [Google Scholar]
  114. 114. 
    Lu F, Wikramasinghe P, Norseen J, Tsai K, Wang P et al. 2010. Genome-wide analysis of host-chromosome binding sites for Epstein-Barr virus nuclear antigen 1 (EBNA1). Virol. J. 7:262
    [Google Scholar]
  115. 115. 
    Coppotelli G, Mughal N, Callegari S, Sompallae R, Caja L et al. 2013. The Epstein-Barr virus nuclear antigen-1 reprograms transcription by mimicry of high mobility group A proteins. Nucleic Acids Res 41:2950–62
    [Google Scholar]
  116. 116. 
    Moquin SA, Thomas S, Whalen S, Warburton A, Fernandez SG et al. 2017. The Epstein-Barr virus episome maneuvers between nuclear chromatin compartments during reactivation. J. Virol. 92:e01413–17
    [Google Scholar]
  117. 117. 
    Jang MK, Shen K, McBride AA 2014. Papillomavirus genomes associate with BRD4 to replicate at fragile sites in the host genome. PLOS Pathog 10:e1004117
    [Google Scholar]
  118. 118. 
    Thorland EC, Myers SL, Persing DH, Sarkar G, McGovern RM et al. 2000. Human papillomavirus type 16 integrations in cervical tumors frequently occur in common fragile sites. Cancer Res 60:5916–21
    [Google Scholar]
  119. 119. 
    Poddar A, Reed SC, McPhillips MG, Spindler JE, McBride AA 2009. The human papillomavirus type 8 E2 tethering protein targets the ribosomal DNA loci of host mitotic chromosomes. J. Virol. 83:640–50
    [Google Scholar]
  120. 120. 
    Sekhar V, McBride AA. 2012. Phosphorylation regulates binding of the human papillomavirus type 8 E2 protein to host chromosomes. J. Virol. 86:10047–58
    [Google Scholar]
  121. 121. 
    Kobayashi T. 2008. A new role of the rDNA and nucleolus in the nucleus-rDNA instability maintains genome integrity. Bioessays 30:267–72
    [Google Scholar]
  122. 122. 
    Penrose KJ, McBride AA. 2000. Proteasome-mediated degradation of the papillomavirus E2-TA protein is regulated by phosphorylation and can modulate viral genome copy number. J. Virol. 74:6031–38
    [Google Scholar]
  123. 123. 
    McBride AA, Howley PM. 1991. Bovine papillomavirus with a mutation in the E2 serine 301 phosphorylation site replicates at a high copy number. J. Virol. 65:6528–34
    [Google Scholar]
  124. 124. 
    Chang SW, Liu WC, Liao KY, Tsao YP, Hsu PH, Chen SL 2014. Phosphorylation of HPV-16 E2 at serine 243 enables binding to Brd4 and mitotic chromosomes. PLOS ONE 9:e110882
    [Google Scholar]
  125. 125. 
    Shire K, Kapoor P, Jiang K, Hing MN, Sivachandran N et al. 2006. Regulation of the EBNA1 Epstein-Barr virus protein by serine phosphorylation and arginine methylation. J. Virol. 80:5261–72
    [Google Scholar]
  126. 126. 
    Duellman SJ, Thompson KL, Coon JJ, Burgess RR 2009. Phosphorylation sites of Epstein-Barr virus EBNA1 regulate its function. J. Gen. Virol. 90:2251–59
    [Google Scholar]
  127. 127. 
    Woodard C, Shamay M, Liao G, Zhu J, Ng AN et al. 2012. Phosphorylation of the chromatin binding domain of KSHV LANA. PLOS Pathog 8:e1002972
    [Google Scholar]
  128. 128. 
    Dreer M, van de Poel S, Stubenrauch F 2017. Control of viral replication and transcription by the papillomavirus E8∧E2 protein. Virus Res 231:96–102
    [Google Scholar]
  129. 129. 
    Dreer M, Fertey J, van de Poel S, Straub E, Madlung J et al. 2016. Interaction of NCOR/SMRT repressor complexes with papillomavirus E8∧E2C proteins inhibits viral replication. PLOS Pathog 12:e1005556
    [Google Scholar]
  130. 130. 
    Straub E, Dreer M, Fertey J, Iftner T, Stubenrauch F 2014. The viral E8∧E2C repressor limits productive replication of human papillomavirus 16. J. Virol. 88:937–47
    [Google Scholar]
  131. 131. 
    Lace MJ, Anson JR, Thomas GS, Turek LP, Haugen TH 2008. The E8∧E2 gene product of human papillomavirus type 16 represses early transcription and replication but is dispensable for viral plasmid persistence in keratinocytes. J. Virol. 82:10841–53
    [Google Scholar]
  132. 132. 
    Stubenrauch F, Hummel M, Iftner T, Laimins LA 2000. The E8∧E2C protein, a negative regulator of viral transcription and replication, is required for extrachromosomal maintenance of human papillomavirus type 31 in keratinocytes. J. Virol. 74:1178–86
    [Google Scholar]
  133. 133. 
    Cardenas-Mora J, Spindler JE, Jang MK, McBride AA 2008. Dimerization of the papillomavirus E2 protein is required for efficient mitotic chromosome association and Brd4 binding. J. Virol. 82:7298–305
    [Google Scholar]
  134. 134. 
    Kurg R, Uusen P, Vosa L, Ustav M 2010. Human papillomavirus E2 protein with single activation domain initiates HPV18 genome replication, but is not sufficient for long-term maintenance of virus genome. Virology 408:159–66
    [Google Scholar]
  135. 135. 
    Sim J, Ozgur S, Lin BY, Yu JH, Broker TR et al. 2008. Remodeling of the human papillomavirus type 11 replication origin into discrete nucleoprotein particles and looped structures by the E2 protein. J. Mol. Biol. 375:1165–77
    [Google Scholar]
  136. 136. 
    Avolio-Hunter TM, Frappier L. 1998. Mechanistic studies on the DNA linking activity of Epstein-Barr nuclear antigen 1. Nucleic Acids Res 26:4462–70
    [Google Scholar]
  137. 137. 
    Deakyne JS, Malecka KA, Messick TE, Lieberman PM 2017. Structural and functional basis for an EBNA1 hexameric ring in Epstein-Barr virus episome maintenance. J. Virol. 91:e01046–17
    [Google Scholar]
  138. 138. 
    Lieberman PM. 2016. Epigenetics and genetics of viral latency. Cell Host Microbe 19:619–28
    [Google Scholar]
  139. 139. 
    Chen HS, Lu F, Lieberman PM 2013. Epigenetic regulation of EBV and KSHV latency. Curr. Opin. Virol. 3:251–59
    [Google Scholar]
  140. 140. 
    McBride AA, Oliveira JG, McPhillips MG 2006. Partitioning viral genomes in mitosis: same idea, different targets. Cell Cycle 5:1499–1502
    [Google Scholar]
/content/journals/10.1146/annurev-virology-092818-015716
Loading
/content/journals/10.1146/annurev-virology-092818-015716
Loading

Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error