1887

Abstract

JC virus (JCV) is the aetiological agent of the demyelinating disease progressive multifocal leukoencephalopathy, an AIDS defining illness and serious complication of mAb therapies. Initial infection probably occurs in childhood. In the working model of dissemination, virus persists in the kidney and lymphoid tissues until immune suppression/modulation causes reactivation and trafficking to the brain where JCV replicates in oligodendrocytes. JCV infection is regulated through binding of host factors such as Spi-B to, and sequence variation in the non-coding control region (NCCR). Although NCCR sequences differ between sites of persistence and pathogenesis, evidence suggests that the virus that initiates infection in the brain disseminates via B-cells derived from latently infected haematopoietic precursors in the bone marrow. Spi-B binds adjacent to TATA boxes in the promoter/enhancer of the PML-associated JCV Mad-1 and Mad-4 viruses but not the non-pathogenic, kidney-associated archetype. The Spi-B-binding site of Mad-1/Mad-4 differs from that of archetype by a single nucleotide, AAAAGGGAAGGA to AAAAGGGAAGGA. Point mutation of the Mad-1 Spi-B site reduced early viral protein large T-antigen expression by up to fourfold. Strikingly, the reverse mutation in the archetype NCCR increased large T-antigen expression by 10-fold. Interestingly, Spi-B protein binds the NCCR sequence flanking the viral promoter/enhancer, but these sites are not essential for early viral gene expression. The effect of mutating Spi-B-binding sites within the JCV promoter/enhancer on early viral gene expression strongly suggests a role for Spi-B binding to the viral promoter/enhancer in the activation of early viral gene expression.

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2012-03-01
2020-01-29
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References

  1. Agostini H. T. , Ryschkewitsch C. F. , Stoner G. L. . ( 1998; ). Rearrangements of archetypal regulatory regions in JC virus genomes from urine. . Res Virol 149:, 163–170. [CrossRef] [PubMed]
    [Google Scholar]
  2. Amemiya K. , Traub R. , Durham L. , Major E. O. . ( 1989; ). Interaction of a nuclear factor-1-like protein with the regulatory region of the human polyomavirus JC virus. . J Biol Chem 264:, 7025–7032.[PubMed]
    [Google Scholar]
  3. Amemiya K. , Traub R. , Durham L. , Major E. O. . ( 1992; ). Adjacent nuclear factor-1 and activator protein binding sites in the enhancer of the neurotropic JC virus. A common characteristic of many brain-specific genes. . J Biol Chem 267:, 14204–14211.[PubMed]
    [Google Scholar]
  4. Andrews N. C. , Faller D. V. . ( 1991; ). A rapid micropreparation technique for extraction of DNA-binding proteins from limiting numbers of mammalian cells. . Nucleic Acids Res 19:, 2499. [CrossRef] [PubMed]
    [Google Scholar]
  5. Ault G. S. , Stoner G. L. . ( 1993; ). Human polyomavirus JC promoter/enhancer rearrangement patterns from progressive multifocal leukoencephalopathy brain are unique derivatives of a single archetypal structure. . J Gen Virol 74:, 1499–1507. [CrossRef] [PubMed]
    [Google Scholar]
  6. Bartel F. O. , Higuchi T. , Spyropoulos D. D. . ( 2000; ). Mouse models in the study of the Ets family of transcription factors. . Oncogene 19:, 6443–6454. [CrossRef] [PubMed]
    [Google Scholar]
  7. Bellizzi A. , Anzivino E. , Ferrari F. , Di Nardo G. , Colosimo M. T. , Fioriti D. , Mischitelli M. , Chiarini F. , Cucchiara S. , Pietropaolo V. . ( 2011; ). Polyomavirus JC reactivation and noncoding control region sequence analysis in pediatric Crohn’s disease patients treated with infliximab. . J Neurovirol 17:, 303–313. [CrossRef] [PubMed]
    [Google Scholar]
  8. Berger J. R. . ( 2010; ). Progressive multifocal leukoencephalopathy and newer biological agents. . Drug Saf 33:, 969–983. [CrossRef] [PubMed]
    [Google Scholar]
  9. Boothpur R. , Brennan D. C. . ( 2010; ). Human polyoma viruses and disease with emphasis on clinical BK and JC. . J Clin Virol 47:, 306–312. [CrossRef] [PubMed]
    [Google Scholar]
  10. Brew B. J. , Davies N. W. , Cinque P. , Clifford D. B. , Nath A. . ( 2010; ). Progressive multifocal leukoencephalopathy and other forms of JC virus disease. . Nat Rev Neurol 6:, 667–679. [CrossRef] [PubMed]
    [Google Scholar]
  11. Carvalho M. , Derse D. . ( 1993; ). The PU.1/Spi-1 proto-oncogene is a transcriptional regulator of a lentivirus promoter. . J Virol 67:, 3885–3890.[PubMed]
    [Google Scholar]
  12. Chen N. N. , Khalili K. . ( 1995; ). Transcriptional regulation of human JC polyomavirus promoters by cellular proteins YB-1 and Pur alpha in glial cells. . J Virol 69:, 5843–5848.[PubMed]
    [Google Scholar]
  13. Damania B. , Alwine J. C. . ( 1996; ). TAF-like function of SV40 large T antigen. . Genes Dev 10:, 1369–1381. [CrossRef] [PubMed]
    [Google Scholar]
  14. Daniel A. M. , Swenson J. J. , Mayreddy R. P. , Khalili K. , Frisque R. J. . ( 1996; ). Sequences within the early and late promoters of archetype JC virus restrict viral DNA replication and infectivity. . Virology 216:, 90–101. [CrossRef] [PubMed]
    [Google Scholar]
  15. Dekoninck A. , Calomme C. , Nizet S. , de Launoit Y. , Burny A. , Ghysdael J. , Van Lint C. . ( 2003; ). Identification and characterization of a PU.1/Spi-B binding site in the bovine leukemia virus long terminal repeat. . Oncogene 22:, 2882–2896. [CrossRef] [PubMed]
    [Google Scholar]
  16. Delbue S. , Sotgiu G. , Fumagalli D. , Valli M. , Borghi E. , Mancuso R. , Marchioni E. , Maserati R. , Ferrante P. . ( 2005; ). A case of a progressive multifocal leukoencephalopathy patient with four different JC virus transcriptional control region rearrangements in cerebrospinal fluid, blood, serum, and urine. . J Neurovirol 11:, 51–57. [CrossRef] [PubMed]
    [Google Scholar]
  17. Elsner C. , Dörries K. . ( 1998; ). Human polyomavirus JC control region variants in persistently infected CNS and kidney tissue. . J Gen Virol 79:, 789–799.[PubMed]
    [Google Scholar]
  18. Erselius J. R. , Jostes B. , Hatzopoulos A. K. , Mosthaf L. , Gruss P. . ( 1990; ). Cell-type-specific control elements of the lymphotropic papovavirus enhancer. . J Virol 64:, 1657–1666.[PubMed]
    [Google Scholar]
  19. Frisque R. J. . ( 1983; ). Regulatory sequences and virus-cell interactions of JC virus. . Prog Clin Biol Res 105:, 41–59.[PubMed]
    [Google Scholar]
  20. Frisque R. J. , Bream G. L. , Cannella M. T. . ( 1984; ). Human polyomavirus JC virus genome. . J Virol 51:, 458–469.[PubMed]
    [Google Scholar]
  21. Gallant S. , Gilkeson G. . ( 2006; ). ETS transcription factors and regulation of immunity. . Arch Immunol Ther Exp (Warsz) 54:, 149–163. [CrossRef] [PubMed]
    [Google Scholar]
  22. Gosert R. , Kardas P. , Major E. O. , Hirsch H. H. . ( 2010; ). Rearranged JC virus non-coding control regions found in progressive multifocal leukoencephalopathy increase virus early gene expression and replication rate. . J Virol 84:, 10448–10456. [CrossRef]
    [Google Scholar]
  23. Hagemeier C. , Bannister A. J. , Cook A. , Kouzarides T. . ( 1993; ). The activation domain of transcription factor PU.1 binds the retinoblastoma (RB) protein and the transcription factor TFIID in vitro: RB shows sequence similarity to TFIID and TFIIB. . Proc Natl Acad Sci U S A 90:, 1580–1584. [CrossRef] [PubMed]
    [Google Scholar]
  24. Hara K. , Sugimoto C. , Kitamura T. , Aoki N. , Taguchi F. , Yogo Y. . ( 1998; ). Archetype JC virus efficiently replicates in COS-7 cells, simian cells constitutively expressing simian virus 40 T antigen. . J Virol 72:, 5335–5342.[PubMed]
    [Google Scholar]
  25. Hochheimer A. , Tjian R. . ( 2003; ). Diversified transcription initiation complexes expand promoter selectivity and tissue-specific gene expression. . Genes Dev 17:, 1309–1320. [CrossRef] [PubMed]
    [Google Scholar]
  26. Jensen P. N. , Major E. O. . ( 2001; ). A classification scheme for human polyomavirus JCV variants based on the nucleotide sequence of the noncoding regulatory region. . J Neurovirol 7:, 280–287. [CrossRef] [PubMed]
    [Google Scholar]
  27. Kerr D. , Chang C. F. , Chen N. , Gallia G. , Raj G. , Schwartz B. , Khalili K. . ( 1994; ). Transcription of a human neurotropic virus promoter in glial cells: effect of YB-1 on expression of the JC virus late gene. . J Virol 68:, 7637–7643.[PubMed]
    [Google Scholar]
  28. Krebs C. J. , McAvoy M. T. , Kumar G. . ( 1995; ). The JC virus minimal core promoter is glial cell specific in vivo. . J Virol 69:, 2434–2442.[PubMed]
    [Google Scholar]
  29. Kumar K. U. , Devireddy L. R. , Tang S. C. , Pater A. , Pater M. M. . ( 1996; ). Human JC virus nuclear factor 1 binding motifs and large tumor antigen region required for transactivation of late promoter. . J Neurochem 67:, 473–481. [CrossRef] [PubMed]
    [Google Scholar]
  30. Laux G. , Dugrillon F. , Eckert C. , Adam B. , Zimber-Strobl U. , Bornkamm G. W. . ( 1994; ). Identification and characterization of an Epstein–Barr virus nuclear antigen 2-responsive cis element in the bidirectional promoter region of latent membrane protein and terminal protein 2 genes. . J Virol 68:, 6947–6958.[PubMed]
    [Google Scholar]
  31. Lindberg R. L. , Achtnichts L. , Hoffmann F. , Kuhle J. , Kappos L. . ( 2008; ). Natalizumab alters transcriptional expression profiles of blood cell subpopulations of multiple sclerosis patients. . J Neuroimmunol 194:, 153–164. [CrossRef] [PubMed]
    [Google Scholar]
  32. Major E. O. . ( 2010; ). Progressive multifocal leukoencephalopathy in patients on immunomodulatory therapies. . Annu Rev Med 61:, 35–47. [CrossRef] [PubMed]
    [Google Scholar]
  33. Major E. O. , Vacante D. A. , Traub R. G. , London W. T. , Sever J. L. . ( 1987; ). Owl monkey astrocytoma cells in culture spontaneously produce infectious JC virus which demonstrates altered biological properties. . J Virol 61:, 1435–1441.[PubMed]
    [Google Scholar]
  34. Manley K. , O’Hara B. A. , Gee G. V. , Simkevich C. P. , Sedivy J. M. , Atwood W. J. . ( 2006; ). NFAT4 is required for JC virus infection of glial cells. . J Virol 80:, 12079–12085. [CrossRef] [PubMed]
    [Google Scholar]
  35. Mao C. , Ray-Gallet D. , Tavitian A. , Moreau-Gachelin F. . ( 1996; ). Differential phosphorylations of Spi-B and Spi-1 transcription factors. . Oncogene 12:, 863–873.[PubMed]
    [Google Scholar]
  36. Marshall L. J. , Major E. O. . ( 2010; ). Molecular regulation of JC virus tropism: insights into potential therapeutic targets for progressive multifocal leukoencephalopathy. . J Neuroimmune Pharmacol 5:, 404–417. [CrossRef] [PubMed]
    [Google Scholar]
  37. Marshall L. J. , Dunham L. , Major E. O. . ( 2010; ). Transcription factor Spi-B binds unique sequences present in the tandem repeat promoter/enhancer of JC virus and supports viral activity. . J Gen Virol 91:, 3042–3052. [CrossRef] [PubMed]
    [Google Scholar]
  38. Martin J. D. , Li P. . ( 1991; ). Enhancer/promoter activities of regulatory regions of representative JC virus isolates. . Arch Virol 120:, 305–311. [CrossRef] [PubMed]
    [Google Scholar]
  39. Martin J. D. , King D. M. , Slauch J. M. , Frisque R. J. . ( 1985; ). Differences in regulatory sequences of naturally occurring JC virus variants. . J Virol 53:, 306–311.[PubMed]
    [Google Scholar]
  40. Marzocchetti A. , Wuthrich C. , Tan C. S. , Tompkins T. , Bernal-Cano F. , Bhargava P. , Ropper A. H. , Koralnik I. J. . ( 2008; ). Rearrangement of the JC virus regulatory region sequence in the bone marrow of a patient with rheumatoid arthritis and progressive multifocal leukoencephalopathy. . J Neurovirol 14:, 455–458. [CrossRef] [PubMed]
    [Google Scholar]
  41. Mayreddy R. P. , Safak M. , Razmara M. , Zoltick P. , Khalili K. . ( 1996; ). Transcription of the JC virus archetype late genome: importance of the kappa B and the 23-base-pair motifs in late promoter activity in glial cells. . J Virol 70:, 2387–2393.[PubMed]
    [Google Scholar]
  42. Messam C. A. , Hou J. , Gronostajski R. M. , Major E. O. . ( 2003; ). Lineage pathway of human brain progenitor cells identified by JC virus susceptibility. . Ann Neurol 53:, 636–646. [CrossRef] [PubMed]
    [Google Scholar]
  43. Monaco M. C. , Sabath B. F. , Durham L. C. , Major E. O. . ( 2001; ). JC virus multiplication in human hematopoietic progenitor cells requires the NF-1 class D transcription factor. . J Virol 75:, 9687–9695. [CrossRef] [PubMed]
    [Google Scholar]
  44. O’Connor P. , Miller D. , Riester K. , Yang M. , Panzara M. , Dalton C. , Miszkiel K. , Khan O. , Rice G. , Sheremata W. . International Natalizumab Trial Group ( 2005; ). Relapse rates and enhancing lesions in a phase II trial of natalizumab in multiple sclerosis. . Mult Scler 11:, 568–572. [CrossRef] [PubMed]
    [Google Scholar]
  45. Pagani E. , Delbue S. , Mancuso R. , Borghi E. , Tarantini L. , Ferrante P. . ( 2003; ). Molecular analysis of JC virus genotypes circulating among the Italian healthy population. . J Neurovirol 9:, 559–566.[PubMed] [CrossRef]
    [Google Scholar]
  46. Petterson M. , Schaffner W. . ( 1987; ). A purine-rich DNA sequence motif present in SV40 and lymphotropic papovavirus binds a lymphoid-specific factor and contributes to enhancer activity in lymphoid cells. . Genes Dev 1:, 962–972. [CrossRef] [PubMed]
    [Google Scholar]
  47. Pongubala J. M. , Nagulapalli S. , Klemsz M. J. , McKercher S. R. , Maki R. A. , Atchison M. L. . ( 1992; ). PU.1 recruits a second nuclear factor to a site important for immunoglobulin kappa 3′ enhancer activity. . Mol Cell Biol 12:, 368–378.[PubMed]
    [Google Scholar]
  48. Ranganathan P. N. , Khalili K. . ( 1993; ). The transcriptional enhancer element, kappa B, regulates promoter activity of the human neurotropic virus, JCV, in cells derived from the CNS. . Nucleic Acids Res 21:, 1959–1964. [CrossRef] [PubMed]
    [Google Scholar]
  49. Rao S. , Matsumura A. , Yoon J. , Simon M. C. . ( 1999; ). SPI-B activates transcription via a unique proline, serine, and threonine domain and exhibits DNA binding affinity differences from PU.1. . J Biol Chem 274:, 11115–11124. [CrossRef] [PubMed]
    [Google Scholar]
  50. Ray D. , Bosselut R. , Ghysdael J. , Mattei M. G. , Tavitian A. , Moreau-Gachelin F. . ( 1992; ). Characterization of Spi-B, a transcription factor related to the putative oncoprotein Spi-1/PU.1. . Mol Cell Biol 12:, 4297–4304.[PubMed]
    [Google Scholar]
  51. Ray-Gallet D. , Tavitian A. , Moreau-Gachelin F. . ( 1996; ). An alternatively spliced isoform of the Spi-B transcription factor. . Biochem Biophys Res Commun 223:, 257–263. [CrossRef] [PubMed]
    [Google Scholar]
  52. Reid C. E. , Li H. , Sur G. , Carmillo P. , Bushnell S. , Tizard R. , McAuliffe M. , Tonkin C. , Simon K. . & other authors ( 2011; ). Sequencing and analysis of JC virus DNA from natalizumab-treated PML patients. . J Infect Dis 204:, 237–244. [CrossRef] [PubMed]
    [Google Scholar]
  53. Rekvig O. . ( 1997; ). Polyoma induced autoimmunity to DNA; experimental systems and clinical observations in human SLE. . Lupus 6:, 325–326. [CrossRef] [PubMed]
    [Google Scholar]
  54. Romagnoli L. , Wollebo H. S. , Deshmane S. L. , Mukerjee R. , Del Valle L. , Safak M. , Khalili K. , White M. K. . ( 2009; ). Modulation of JC virus transcription by C/EBPβ. . Virus Res 146:, 97–106. [CrossRef] [PubMed]
    [Google Scholar]
  55. Roux D. , Bouldouyre M. A. , Mercier-Delarue S. , Seilhean D. , Zagdanski A. M. , Delaugerre C. , Simon F. , Molina J. M. , Legoff J. . ( 2011; ). JC virus variant associated with cerebellar atrophy in a patient with AIDS. . J Clin Microbiol 49:, 2196–2199. [CrossRef] [PubMed]
    [Google Scholar]
  56. Safak M. , Gallia G. L. , Ansari S. A. , Khalili K. . ( 1999; ). Physical and functional interaction between the Y-box binding protein YB-1 and human polyomavirus JC virus large T antigen. . J Virol 73:, 10146–10157.[PubMed]
    [Google Scholar]
  57. Sock E. , Enderich J. , Wegner M. . ( 1999; ). The J domain of papovaviral large tumor antigen is required for synergistic interaction with the POU-domain protein Tst-1/Oct6/SCIP. . Mol Cell Biol 19:, 2455–2464.[PubMed]
    [Google Scholar]
  58. Su G. H. , Ip H. S. , Cobb B. S. , Lu M. M. , Chen H. M. , Simon M. C. . ( 1996; ). The Ets protein Spi-B is expressed exclusively in B cells and T cells during development. . J Exp Med 184:, 203–214. [CrossRef] [PubMed]
    [Google Scholar]
  59. Tan C. S. , Dezube B. J. , Bhargava P. , Autissier P. , Wüthrich C. , Miller J. , Koralnik I. J. . ( 2009; ). Detection of JC virus DNA and proteins in the bone marrow of HIV-positive and HIV-negative patients: implications for viral latency and neurotropic transformation. . J Infect Dis 199:, 881–888. [CrossRef] [PubMed]
    [Google Scholar]
  60. Tan C. S. , Ellis L. C. , Wüthrich C. , Ngo L. , Broge T. A. Jr , Saint-Aubyn J. , Miller J. S. , Koralnik I. J. . ( 2010; ). JC virus latency in the brain and extraneural organs of patients with and without progressive multifocal leukoencephalopathy. . J Virol 84:, 9200–9209. [CrossRef] [PubMed]
    [Google Scholar]
  61. Vaz B. , Cinque P. , Pickhardt M. , Weber T. . ( 2000; ). Analysis of the transcriptional control region in progressive multifocal leukoencephalopathy. . J Neurovirol 6:, 398–409. [CrossRef] [PubMed]
    [Google Scholar]
  62. Wasylyk B. , Hahn S. L. , Giovane A. . ( 1993; ). The Ets family of transcription factors. [erratum appears in Eur J Biochem 1993 Aug 1;215(3):907]. Eur J Biochem 211:, 7–18. [CrossRef] [PubMed]
    [Google Scholar]
  63. Weintraub S. J. , Chow K. N. , Luo R. X. , Zhang S. H. , He S. , Dean D. C. . ( 1995; ). Mechanism of active transcriptional repression by the retinoblastoma protein. . Nature 375:, 812–816. [CrossRef] [PubMed]
    [Google Scholar]
  64. Yogo Y. , Kitamura T. , Sugimoto C. , Ueki T. , Aso Y. , Hara K. , Taguchi F. . ( 1990; ). Isolation of a possible archetypal JC virus DNA sequence from nonimmunocompromised individuals. . J Virol 64:, 3139–3143.[PubMed]
    [Google Scholar]
  65. Zhai W. , Tuan J. A. , Comai L. . ( 1997; ). SV40 large T antigen binds to the TBP-TAF(I) complex SL1 and coactivates ribosomal RNA transcription. . Genes Dev 11:, 1605–1617. [CrossRef] [PubMed]
    [Google Scholar]
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