The Polyomavirus, JCV, and Its Involvement in Human Disease

  • Kamel Khalili
  • Jennifer Gordon
  • Martyn K. White
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 577)


The human neurotropic polyomavirus, JC virus (JCV), is the etiologic agent of progressive multifocal leukoencephalopathy (PML), a fatal demyelinating disease of the central nervous system that occurs mainly in immunosuppressed patients. JCV has also been found to be associated with human tumors of the brain and other organs. In this chapter, we describe JC virus and its role in human diseases.


Malignant Peripheral Nerve Sheath Tumor Progressive Multifocal Leukoencephalopathy Human Immune Deficiency Virus Human Polyomavirus Cellular Nucleic Acid Binding Protein 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Cole CN. Polyomavirinae: The viruses and their replication. In: Fields BN, Knipe DM, Howley PM, eds. Fundamental Virology. 3rd ed. Lippincott, Williams & Wilkins, Philadelphia, 917–946.Google Scholar
  2. 2.
    Imperiale MJ. The human polyoma viruses: An overview. In: Khalili K, Stoner GL, eds. Human polyomaviruses: Molecular and clinical perspective. New York: Wiley-Liss Inc., 2001:53–71.Google Scholar
  3. 3.
    Stewart SE, Eddy BE, Borgese NG. Neoplasms in mice inoculated with a tumor agent carried in tissue culture. J Natl Cancer Inst 1958; 20:1223–1243.PubMedGoogle Scholar
  4. 4.
    Sweet BH, Hilleman MR. The vacuolating virus, SV40. Proc Soc Exp Biol Med 1960; 105:420–427.PubMedGoogle Scholar
  5. 5.
    Gardner SD, Field AM, Coleman DV et al. New human papovavirus (B.K.) isolated from urine after renal transplantation. Lancet 1971; 1:1253–1257.PubMedCrossRefGoogle Scholar
  6. 6.
    Padgett BL, Walker DL, ZuRhein GM et al. Cultivation of papova-like virus from human brain with progressive mutifocal leucoencephalopathy. Lancet 1971; 1:1257–1260.PubMedCrossRefGoogle Scholar
  7. 7.
    Komagome R, Sawa H, Suzuki T et al. Oligosaccharides as receptors for JC virus. J Virol 2002; 76:12992–13000.PubMedCrossRefGoogle Scholar
  8. 8.
    Liu CK, Wei G, Atwood WJ. Infection of glial cells by the human polyomavirus JC is mediated by an N-linked glycoprotein containing terminal alpha(2-6)-linked sialic acids. J Virol 1998; 72:4643–4649.PubMedGoogle Scholar
  9. 9.
    Norkin LC. Simian virus 40 infection via MHC class I molecules and caveolae. Immunol Rev 1999; 168:13–22.PubMedCrossRefGoogle Scholar
  10. 10.
    Suzuki S, Sawa H, Komagome R et al. Broad distribution of the JC virus receptor contrasts with a marked cellular restriction of virus replication. Virology 2001; 286:100–112.PubMedCrossRefGoogle Scholar
  11. 11.
    Eash S, Tavares R, Stopa EG et al. Differential distribution of the JC virus receptor-type sialic acid in normal human tissues. Am J Pathol 2004; 164:419–428.PubMedGoogle Scholar
  12. 12.
    Wei G, Liu CK, Atwood WJ. JC virus binds to primary human glial cells, tonsillar stromal cells and B-lymphocytes, but not to T-lymphocytes. J Neurovirol 2000; 6:127–136.PubMedCrossRefGoogle Scholar
  13. 13.
    Anderson HA, Chen Y, Norkin LC. Bound simian virus 40 translocates to caveolin-enriched membrane domains, and its entry is inhibited by drugs that selectively disrupt caveolae. Mol Biol Cell 1996; 7:1825–1834.PubMedGoogle Scholar
  14. 14.
    Pho MT, Ashok A, Atwood WJ. JC virus enters human glial cells by clathrin-dependent receptor-mediated endocytosis. J Virol 2000; 74:2288–2292.PubMedCrossRefGoogle Scholar
  15. 15.
    Querbes W, Benmerah A, Tosoni D et al. A JC virus-induced signal is required for infection of glial cells by a clathrin-and eps15-dependent pathway. J Virol 2004; 78:250–256.PubMedCrossRefGoogle Scholar
  16. 16.
    Qu Q, Sawa H, Suzuki T et al. Nuclear entry mechanism of the human polyomavirus JC virus like particle: Role of importins and the nuclear pore complex. J Biol Chem 2004; 279:27735–27742.PubMedCrossRefGoogle Scholar
  17. 17.
    Henson JW, Schnitker BL, Lee T-S et al. Cell-specific activation of the glial-specific JC virus early promoter by large T antigen. J Biol Chem 1995; 270:13240–13245.PubMedCrossRefGoogle Scholar
  18. 18.
    Kim H-S, Henson JW, Frisque RJ. Transcription and replication in the human polyomaviruses. In: Khalili K, Stoner GL, eds. Human polyomaviruses: Molecular and clinical perspective. New York: Wiley-Liss Inc., 2001:73–126.Google Scholar
  19. 19.
    Kenny S, Natarajan V, Strike D et al. JC virus enhancer-promoter activity in human brain cells. Science 1984; 226:1337–1339.CrossRefGoogle Scholar
  20. 20.
    Trapp BD, Small JA, Pulley M et al. Dysmyelination in transgenic mice containing JC virus early region. Ann Neurol 1988; 23:38–48.PubMedCrossRefGoogle Scholar
  21. 21.
    Feigenbaum L, Hinrichs SH, Jay G. JC virus and SV40 enhancers and transforming proteins: Role in determining tissue specificity and pathogenicity in transgenic mice. J Virol 1992; 66:1176–1182.PubMedGoogle Scholar
  22. 22.
    Ahmed S, Chowdhury M, Khalili K. Regulation of a human neurotropic virus promoter, JCV(E): Identification of a novel activator domain located upstream from the 98 bp enhancer promoter region. Nucleic Acids Res 1990; 18:7417–7423.PubMedCrossRefGoogle Scholar
  23. 23.
    Ahmed S, Rappaport J, Tada H et al. A nuclear protein derived from brain cells stimulates transcription of the human neurotropic virus promoter JCVE, in vitro. J Biol Chem 1990; 265:13899–13905.PubMedGoogle Scholar
  24. 24.
    Raj G, Khalili K. Transcriptional regulation: Lessons from the human neurotropic polyomavirus, JCV. Virology 1995; 213:283–291.PubMedCrossRefGoogle Scholar
  25. 25.
    Major EO, Amemiya K, Tornatore CS et al. Pathogenesis and molecular biology of progressive multifocal leukoencephalopathy, the JC virus-induced demyelinating disease of the human brain. Clin Microbiol Rev 1992; 5:49–73.PubMedGoogle Scholar
  26. 26.
    Monaco MC, Jensen PN, Hou J et al. Detection of JC virus DNA in human tonsil tissue: Evidence for site of initial viral infection. J Virol 1998; 72:9918–9923.PubMedGoogle Scholar
  27. 27.
    Bofill-Mas S, Girones R. Excretion and transmission of JCV in human populations. J Neurovirol 2001; 7:345–349.PubMedCrossRefGoogle Scholar
  28. 28.
    Bofill-Mas S, Formiga-Cruz M, Clemente-Casares P et al. Potential transmission of human polyomaviruses through the gastrointestinal tract after exposure to virions or viral DNA. J Virol 2001; 75:10290–10299.PubMedCrossRefGoogle Scholar
  29. 29.
    Bofill-Mas S, Clemente-Casares P, Major EO et al. Analysis of the excreted JC virus strains and their potential oral transmission. J Neurovirol 2003; 9:498–507.PubMedCrossRefGoogle Scholar
  30. 30.
    Laghi L, Randolph AE, Chauhan DP et al. JC virus DNA is present in the mucosa of the human colon and in colorectal cancers. Proc Natl Acad Sci USA 1999; 96:7484–7489.PubMedCrossRefGoogle Scholar
  31. 31.
    Ricciardiello L, Laghi L, Ramamirtham P et al. JC virus DNA sequences are frequently present in the human upper and lower gastrointestinal tract. Gastroenterology 2000; 119:1228–1235.PubMedCrossRefGoogle Scholar
  32. 32.
    Chesters PM, Heritage J, McCance DJ. Persistence of DNA sequences of BK virus and JC virus in normal human tissues and in diseased tissues. J Infect Dis 1983; 147:676–684.PubMedGoogle Scholar
  33. 33.
    Weber F, Goldmann C, Kramer M et al. Cellular and humoral immune response in progressive multifocal leukoencephalopathy. Ann Neurol 2001; 49:636–642.PubMedCrossRefGoogle Scholar
  34. 34.
    Gordon J, Khalili K. The human polyomavirus, JCV, and neurological diseases (review). Int J Mol Med 1998; 1:647–655.PubMedGoogle Scholar
  35. 35.
    Safak M, Khalili K. An overview: Human polyomavirus JC virus and its associated disorders. J Neurovirol 2003; 9(Suppl 1):3–9.PubMedCrossRefGoogle Scholar
  36. 36.
    Berger JR. Progressive multifocal leukoencephalopathy in acquired immuno-deficiency syndrome: Explaining the high incidence and disproportionate frequency of the illness relative to other immunosuppressive conditions. J Neurovirol 2003; 9(Suppl 1):38–41.PubMedCrossRefGoogle Scholar
  37. 37.
    Berger JR, Concha M. Progressive multifocal leukoencephalopathy: The evolution of a disease once considered rare. J Neurovirol 1995; 1:5–18.PubMedCrossRefGoogle Scholar
  38. 38.
    Berger JR, Kaszovitz B, Post MJ et al. Progressive multifocal leukoencephalopathy associated with human immunodeficiency virus infection. A review of the literature with a report of sixteen cases. Ann Intern Med 1987; 107:78–87.PubMedGoogle Scholar
  39. 39.
    Berger JR, Chauhan A, Galey D et al. Epidemiological evidence and molecular basis of interactions between HIV and JC virus. J Neurovirol 2001; 7:329–338.PubMedCrossRefGoogle Scholar
  40. 40.
    Brooks BR, Walker DL. Progressive multifocal leukoencephalopathy. Neurol Clin 1984; 2:299–313.PubMedGoogle Scholar
  41. 41.
    Gasnault J, Kahraman M, de Goer de Herve MG et al. Critical role of JC virus-specific CD4 T-cell responses in preventing progressive multifocal leukoencephalopathy. AIDS 2003; 17:1443–1449.PubMedCrossRefGoogle Scholar
  42. 42.
    Power C, Kong PA, Crawford TO et al. Cerebral white matter changes in acquired immunodeficiency syndrome dementia: Alterations of the blood-brain barrier. Ann Neurol 1993; 34:339–350.PubMedCrossRefGoogle Scholar
  43. 43.
    Gallia GL, Houff SA, Major EO et al. Review: JC virus infection of lymphocytes—revisited. J Infect Dis 1997; 176:1603–1609.PubMedGoogle Scholar
  44. 44.
    Chowdhury M, Taylor JP, Tada H et al. Regulation of the human neurotropic virus promoter by JCV-T antigen and HIV-1 tat protein. Oncogene 1990; 5:1737–1742.PubMedGoogle Scholar
  45. 45.
    Tada H, Rappaport J, Lashgari M et al. Trans-activation of the JC virus late promoter by the tat protein of type 1 human immunodeficiency virus in glial cells. Proc Natl Acad Sci USA 1990; 87:3479–3483.PubMedCrossRefGoogle Scholar
  46. 46.
    Chowdhury M, Kundu M, Khalili K. GA/GC-rich sequence confers Tat responsiveness to human neurotropic virus promoter, JCVL, in cells derived from central nervous system. Oncogene 1993; 8:887–892.PubMedGoogle Scholar
  47. 47.
    Krachmarov CP, Chepenik LG, Barr-Vagell S et al. Activation of the JC virus Tat-responsive transcriptional control element by association of the Tat protein of human immunodeficiency virus 1 with cellular protein Pur alpha. Proc Natl Acad Sci USA 1996; 93:14112–14117.PubMedCrossRefGoogle Scholar
  48. 48.
    Daniel DC, Wortman MJ, Schiller RJ et al. Coordinate effects of human immunodeficiency virus type 1 protein Tat and cellular protein Puralpha on DNA replication initiated at the JC virus origin. J Gen Virol 2001; 82:1543–1553.PubMedGoogle Scholar
  49. 49.
    Del Valle L, Croul S, Morgello S et al. Detection of HIV-1 Tat and JCV capsid protein, VP1, in AIDS brain with progressive multifocal leukoencephalopathy. J Neurovirol 2000; 6:221–228.PubMedCrossRefGoogle Scholar
  50. 50.
    Ensoli B, Buonaguro L, Barillari G et al. Release, uptake, and effects of extracellular human immunodeficiency virus type 1 Tat protein on cell growth and viral transactivation. J Virol 1993; 67:277–287.PubMedGoogle Scholar
  51. 51.
    Frankel AD, Pabo CO. Cellular uptake of the tat protein from human immunodeficiency virus. Cell 1988; 55:1189–1193.PubMedCrossRefGoogle Scholar
  52. 52.
    Chepenik LG, Tretiakova AP, Krachmarov CP et al. The single-stranded DNA binding protein, Purα, binds HIV-1 TAR RNA and activates HIV-1 transcription. Gene 1998; 210:37–44.PubMedCrossRefGoogle Scholar
  53. 53.
    Gallia GL, Darbinian N, Tretiakova A et al. Association of HIV-1 Tat with the cellular protein, Puralpha, is mediated by RNA. Proc Natl Acad Sci USA 1999; 96:11572–11577.PubMedCrossRefGoogle Scholar
  54. 54.
    Wortman MJ, Krachmarov CP, Kim JH et al. Interaction of HIV-1 Tat with Puralpha in nuclei of human glial cells: Characterization of RNA-mediated protein-protein binding. J Cell Biochem 2000; 77:65–74.PubMedCrossRefGoogle Scholar
  55. 55.
    Darbinian N, Sawaya BE, Khalili K et al. Functional interaction between cyclin T1/cdk9 and Puralpha determines the level of TNFalpha promoter activation by Tat in glial cells. J Neuroimmunol 2001; 121:3–11.PubMedCrossRefGoogle Scholar
  56. 56.
    Rappaport J, Joseph J, Croul S et al. Molecular pathway involved in HIV-1-induced CNS pathology: Role of viral regulatory protein, Tat. J Leukoc Biol 1999; 65:458–465.PubMedGoogle Scholar
  57. 57.
    Bonwetsch R, Croul S, Richardson MW et al. Role of HIV-1 Tat and CC chemokine MIP-1alpha in the pathogenesis of HIV associated central nervous system disorders. J Neurovirol 1999; 5:685–694.PubMedCrossRefGoogle Scholar
  58. 58.
    Enam S, Sweet TM, Amini S et al. Evidence for involvement of transforming growth factor betal signaling pathway in activation of JC virus in human immunodeficiency virus 1-associated progress sive multifocal leukoencephalopathy. Arch Pathol Lab Med 2004; 128:282–291.PubMedGoogle Scholar
  59. 59.
    Richardson-Burns SM, Kleinschmidt-DeMasters BK, DeBiasi RL et al. Progressive multifocal leukoencephalopathy and apoptosis of infected oligodendrocytes in the central nervous system of patients with and without AIDS. Arch Neurol 2004; 59:1930–1936.CrossRefGoogle Scholar
  60. 60.
    Ariza A, Mate JL, Serrano S et al. DNA amplification in glial cells of progressive multifocal leukoencephalopathy: An image analysis study. J Neuropathol Exp Neurol 1996; 55:729–733.PubMedCrossRefGoogle Scholar
  61. 61.
    Ariza A, Mate JL, Fernandez-Vasalo A et al. p53 and proliferating cell nuclear antigen expression in JC virus-infected cells of progressive multifocal leukoencephalopathy. Hum Pathol 1994; 25:1341–1345.PubMedCrossRefGoogle Scholar
  62. 62.
    Lammie GA, Beckett A, Courtney R et al. An immunohistochemical study of p53 and proliferating cell nuclear antigen expression in progressive multifocal leukoencephalopathy. Acta Neuropathol 1994; 88:465–471.PubMedCrossRefGoogle Scholar
  63. 63.
    Del Valle L, Gordon J, Ferrante P et al. JC virus in experimental and clinical brain tumorigenesis. In: Khalili K, Stoner GL, eds. Human polyomaviruses: Molecular and clinical perspective. New York: Wiley-Liss Inc., 2001:409–430.Google Scholar
  64. 64.
    London WT, Houff SA, Madden DL et al. Brain tumors in owl monkeys inoculated with a human polyomavirus (JC virus). Science 1978; 201:1246–1249.PubMedCrossRefGoogle Scholar
  65. 65.
    London WT, Houff SA, McKeever PE et al. Viral-induced astrocytomas in squirrel monkeys. In: Sever JL, Madden DL, eds. Polyomaviruses and human neurological diseases. New York: Alan R Liss Inc., 1983:227–237.Google Scholar
  66. 66.
    Miller NR, McKeever PE, London W et al. Brain tumors of owl monkeys inoculated with JC virus contain the JC virus genome. J Virol 1984; 49:848–856.PubMedGoogle Scholar
  67. 67.
    Khalili K, Del Valle L, Otte J et al. Human neurotropic polyomavirus, JCV, and its role in carcinogenesis. Oncogene 2003; 22:5181–5191.PubMedCrossRefGoogle Scholar
  68. 68.
    Small JA, Khoury G, Jay G et al. Early regions of JC virus and BK virus induce distinct and tissue-specific tumors in transgenic mice. Proc Natl Acad Sci USA 1986; 83:8288–8292.PubMedCrossRefGoogle Scholar
  69. 69.
    Small JA, Scangos GA, Cork L et al. The early region of human papovavirus JC induces dysmyelination in transgenic mice. Cell 1986; 46:13–18.PubMedCrossRefGoogle Scholar
  70. 70.
    Franks RR, Rencic A, Gordon J et al. Formation of undifferentiated mesenteric tumors in transgenic mice expressing human neurotropic polyomavirus early protein T-antigen. Oncogene 1996; 12:2573–2578.PubMedGoogle Scholar
  71. 71.
    Gordon J, Del Valle L, Otte J et al. Pituitary neoplasia induced by expression of human neurotropic polyomavirus, JCV, early genome in transgenic mice. Oncogene 2000; 19:4840–4846.PubMedCrossRefGoogle Scholar
  72. 72.
    Shollar D, Valle LD, Khalili K et al. JCV T-antigen interacts with the neurofibromatosis type 2 gene product in a transgenic mouse model of malignant peripheral nerve sheath tumors. Oncogene 2004; 23:5459–5467.PubMedCrossRefGoogle Scholar
  73. 73.
    Krynska B, Otte J, Franks R et al. Human ubiquitous JCV•CY T-antigen gene induces brain tumors in experimental animals. Oncogene 1999; 18:39–46.PubMedCrossRefGoogle Scholar
  74. 74.
    Gallia GL, Safak M, Khalili K. Interaction of single-stranded DNA binding protein, Purα, with human polyomavirus, JCV, early protein, T-antigen. J Biol Chem 1998; 273:32662–32669.PubMedCrossRefGoogle Scholar
  75. 75.
    Rencic A, Gordon J, Otte J et al. Detection of JC virus DNA sequence and expression of the viral oncoprotein, tumor antigen, in brain of immunocompetent patient with oligoastrocytoma. Proc Natl Acad Sci USA 1996; 93:7352–7357.PubMedCrossRefGoogle Scholar
  76. 76.
    Del Valle L, Gordon J, Assimakopolou M et al. Detection of JC virus DNA sequences and expression of the viral regulatory protein, T-antigen, in tumors of the central nervous system. Cancer Res 2001; 61:4287–4293.PubMedGoogle Scholar
  77. 77.
    Krynska B, Del Valle L, Croul S et al. Detection of human neurotropic JC virus DNA sequence and expression of the viral oncogenic protein in pediatric medulloblastomas. Proc Natl Acad Sci USA 1999; 96:11519–11524.PubMedCrossRefGoogle Scholar
  78. 78.
    Del Valle L, Gordon J, Enam S et al. Expression of human neurotropic polyomavirus JCV late gene product Agnoprotein in human medulloblastoma. J Natl Cancer Inst 2002; 94:267–273.PubMedGoogle Scholar
  79. 79.
    Boldorini R, Caldarelli-Stefano R, Monga G et al. PCR detection of JC virus DNA in the brain tissue of a 9-year-old child with pleomorphic xanthoastrocytoma. J Neurovirol 1998; 4:242–245.PubMedCrossRefGoogle Scholar
  80. 80.
    Enam S, Del Valle L, Lara C et al. Association of human polyomavirus JCV with colon cancer: Evidence for interaction of viral T-antigen and beta-catenin. Cancer Res 2002; 62:7093–7101.PubMedGoogle Scholar
  81. 81.
    Caldarelli-Stefano R, Boldorini R, Monga G et al. JC virus in human glial-derived tumors. Hum Pathol 2000; 31:394–395.PubMedCrossRefGoogle Scholar
  82. 82.
    Del Valle L, Enam S, Lara C et al. Detection of JC polyomavirus DNA sequences and cellular localization of T-antigen and agnoprotein in oligodendrogliomas. Clin Cancer Res 200b; 8:3332–3340.Google Scholar
  83. 83.
    Del Valle L, Delbue S, Gordon J et al. Expression of JC virus T-antigen in a patient with multiple sclerosis and glioblastoma multiforme. Neurology 2002; 58:895–900.PubMedGoogle Scholar
  84. 84.
    Del Valle L, Enam S, Lara C et al. Primary central nervous system lymphoma expressing the human neurotropic polyomavirus, JC virus, genome. J Virol 2004; 78:3462–3469.PubMedCrossRefGoogle Scholar
  85. 85.
    Gan DD, Khalili K. Interaction between JCV large T-antigen and beta-catenin. Oncogene 2004; 23:483–490.PubMedCrossRefGoogle Scholar
  86. 86.
    zur Hausen H. Viruses in human cancers. Eur J Cancer 1999; 35:1878–1885.PubMedCrossRefGoogle Scholar
  87. 87.
    White MK, Khalili K. Signaling pathways and polyomavirus oncoproteins: Importance in malign nant transformation. Gene Ther Mol Biol 2004; 8:19–30.Google Scholar
  88. 88.
    White MK, Khalili K. Polyomaviruses and human cancer: Molecular mechanisms underlying patterns of tumorigenesis. Virology 2004; 324:1–16.PubMedCrossRefGoogle Scholar
  89. 89.
    Cress WD, Nevins JR. Use of the E2F transcription factor by DNA tumor virus regulatory proteins. Curr Top Microbiol Immunol 1996; 208:63–78.PubMedGoogle Scholar
  90. 90.
    Krynska B, Gordon J, Otte J et al. Role of cell cycle regulators in tumor formation in transgenic mice expressing the human neurotropic virus, JCV, early protein. J Cell Biochem 1997; 67:223–230.PubMedCrossRefGoogle Scholar
  91. 91.
    Tavis JE, Trowbridge PW, Frisque RJ. Converting the JCV T antigen Rb binding domain to that of SV40 does not alter JCVs limited transforming activity but does eliminate viral viability. Virology 1994; 199:384–392.PubMedCrossRefGoogle Scholar
  92. 92.
    Bollag B, Chuke WF, Frisque RJ. Hybrid genomes of the polyomaviruses JC virus, BK virus, and simian virus 40: Identification of sequences important for efficient transformation. J Virol 1989; 63:863–872.PubMedGoogle Scholar
  93. 93.
    Lassak A, Del Valle L, Peruzzi F et al. Insulin receptor substrate 1 translocation to the nucleus by the human JC virus T-antigen. J Biol Chem 2002; 277:17231–17238.PubMedCrossRefGoogle Scholar
  94. 94.
    Theile M, Grabowski G. Mutagenic activity of BKV and JCV in human and other mammalian cells. Arch Virol 1990; 113:221–233.PubMedCrossRefGoogle Scholar
  95. 95.
    Ricciardiello L, Baglioni M, Giovannini C et al. Induction of chromosomal instability in colonic cells by the human polyomavirus JC virus. Cancer Res 2003; 63:7256–7262.PubMedGoogle Scholar
  96. 96.
    Trojanek J, Ho T, Del Valle L et al. T-antigen from human polyomavirus JC attenuates faithful DNA repair by forcing nuclear interaction between IRS-1 and Rad51. Mol Cell 2004; in press.Google Scholar
  97. 97.
    Ray FA, Peabody DS, Cooper JL et al. SV40 T antigen alone drives karyotype instability that precedes neoplastic transformation of human diploid fibroblasts. J Cell Biochem 1990; 42:13–31.PubMedCrossRefGoogle Scholar
  98. 98.
    Ray FA, Meyne J, Kraemer PM. SV40 T antigen induced chromosomal changes reflect a process that is both clastogenic and aneuploidogenic and is ongoing throughout neoplastic progression of human fibroblasts. Mutat Res 1992; 284:265–273.PubMedGoogle Scholar
  99. 99.
    Digweed M, Demuth I, Rothe S et al. SV40 large T-antigen disturbs the formation of nuclear DNA-repair foci containing MRE11. Oncogene 2002; 21:4873–4878.PubMedCrossRefGoogle Scholar
  100. 100.
    Darbinyan A, Darbinian N, Safak M et al. Evidence for dysregulation of cell cycle by human polyomavirus, JCV, late auxiliary protein. Oncogene 2002; 21:5574–5581.PubMedCrossRefGoogle Scholar
  101. 101.
    Darbinyan A, Siddiqui K, Slonina D et al. Role of JCV agnoprotein in DNA repair. J Virol 2004; 78:8593–8600.PubMedCrossRefGoogle Scholar
  102. 102.
    Martin RG, Setlow VP, Edwards CA et al. The roles of the simian virus 40 tumor antigens in transformation of Chinese hamster lung cells. Cell 1979; 17:635–643.PubMedCrossRefGoogle Scholar
  103. 103.
    Sleigh MJ, Topp WC, Hanich R et al. Mutants of SV40 with an altered small t protein are reduced in their ability to transform cells. Cell 1978; 14:79–88.PubMedCrossRefGoogle Scholar
  104. 104.
    Pallas DC, Shahrik LK, Martin BL et al. Polyoma small and middle T antigens and SV40 small tantigen form stable complexes with protein phosphatase 2A. Cell 1990; 12:167–176.CrossRefGoogle Scholar
  105. 105.
    Radhakrishnan S, Otte J, Enam S et al. JC virus-induced changes in cellular gene expression in primary human astrocytes. J Virol 2003; 77:10638–10644.PubMedCrossRefGoogle Scholar
  106. 106.
    Carbone M, Rudzinski J, Bocchetta M. High throughput testing of the SV40 large T antigen binding to cellular p53 identifies putative drugs for the treatment of SV40-related cancers. Virology 2003; 315:409–414.PubMedCrossRefGoogle Scholar
  107. 107.
    Waheed I, Guo ZS, Chen GA et al. Antisense to SV40 early gene region induces growth arrest and apoptosis in T-antigen-positive human pleural mesothelioma cells. Cancer Res 1999; 59:6068–6073.PubMedGoogle Scholar
  108. 108.
    Radhakrishnan S, Gordon J, Del Valle L et al. Intracellular approach for blocking JCV gene expression using RNA interference during viral infection. J Virol 2004; 78:7264–7269.PubMedCrossRefGoogle Scholar

Copyright information

© and Springer Science+Business Media 2006

Authors and Affiliations

  • Kamel Khalili
    • 1
  • Jennifer Gordon
    • 1
  • Martyn K. White
    • 1
  1. 1.Center for Neurovirology and Cancer BiologyTemple UniversityPhiladelphiaUSA

Personalised recommendations