Pharmacotherapeutic Options for the Management of Human Polyomaviruses

  • Julie Roskopf
  • Jennifer Trofe
  • Robert J. Stratta
  • Nasimul Ahsan
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 577)


Polyomaviruses [BK virus (BKV), JC virus (JCV) and simian virus 40 (SV40)] have been known to be associated with diseases in humans for over thirty years. BKV-associated nephropathy and JCV-induced progressive multifocal leukoencephalopathy (PML) were for many years rare diseases occurring only in patients with underlying severe impaired immunity. Over the past decade, the use of more potent immunosuppression (IS) in transplantation, and the Acquired Immune Deficiency Syndrome (AIDS) epidemic, have coincided with a significant increase in the prevalence of these viral complications. Prophylactic and therapeutic interventions for human polyomavirus diseases are limited by our current understanding of polyomaviral pathogenesis. Clinical trials are limited by small numbers of patients affected with clinically significant diseases, lack of defined risk factors and disease definitions, no proven effective treatment and the overall significant morbidity and mortality associated with these diseases. This chapter will focus on a review of the current and future research related to therapeutic targets and interventions for polyomavirus-associated diseases.


Acute Rejection Progressive Multifocal Leukoen Graft Loss Progressive Multifocal Leukoencephalopathy Hemorrhagic Cystitis 
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.
    Shah KV. Polyomaviruses. In: Fields BN, Knipe DM, eds. Fields Virology. 3rd ed. Philadelphia: Lippincott-Raven, 1996:2027–43.Google Scholar
  2. 2.
    Gardner SD, Field AM, Coleman DV et al. New human papovavirus (B.K.) isolated from urine after renal transplantation. Lancet 1971; 1(7712):1253–7.PubMedGoogle Scholar
  3. 3.
    Padgett BL, Walker DL, ZuRhein GM et al. Cultivation of papova-like virus from human brain with progressive multifocal leucoencephalopathy. Lancet 1971; 1(7712):1257–60.PubMedGoogle Scholar
  4. 4.
    Knowles W. The epidemiology of BK virus and the occurence of antigenic and genomic subtypes. In: Khalili K, Stoner GL, eds. Human Polyomaviruses: Molecular and Clinical Perspectives. New York: Wiley-Liss, 2001:527–60.Google Scholar
  5. 5.
    Major EO. Human polyomavirus. In: Knipe DM, Howley PM, eds. Fields Virology. 4th ed. Philadelphia: Lippincott Williams and Wilkins, 2001:2:2175–96.Google Scholar
  6. 6.
    Houff SA, Major EO, Katz DA et al. Involvement of JC virus-infected mononuclear cells from the bone marrow and spleen in the pathogenesis of progressive multifocal leukoencephalopathy. N Engl J Med 1988; 318(5):301–5.PubMedGoogle Scholar
  7. 7.
    Kahan AV, Coleman DV, Koss LG. Activation of human polyomavirus infection — detection by cytologic techniques. Am J Clin Pathol 1980; 74:326–32.PubMedGoogle Scholar
  8. 8.
    Coleman DV, Wolfendale MR, Daniel RA et al. A prospective study of human polyomavirus infection in pregnancy. J Infect Dis 1980; 142(1):1–8.PubMedGoogle Scholar
  9. 9.
    Agha IA, Brennan DC. BK virus and current immunosuppressive therapy. Graft 2002; 5(Suppl):S65–72.Google Scholar
  10. 10.
    Hirsch HH, Knowles W, Dickenmann M et al. Prospective study of polyomavirus type BK replication and nephropathy in renal-transplant recipients. N Engl J Med 2002; 347(7):488–96.PubMedGoogle Scholar
  11. 11.
    Mylonakis E, Goes N, Rubin RH et al. BK virus in solid organ transplant recipients: An emerging syndrome. Transplantation 2001; 72(10):1587–92.PubMedGoogle Scholar
  12. 12.
    Domes K, Loeber G, Meixensberger J. Association of polyomaviruses JC, SV40, and BK with human brain tumors. Virology 1987; 160(1):268–70.Google Scholar
  13. 13.
    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(4):267–73.PubMedGoogle Scholar
  14. 14.
    Khalili K. Human neurotropic JC virus and its association with brain tumors. Dis Markers 2001; 17(3):143–7.PubMedGoogle Scholar
  15. 15.
    Boldorini R, Pagani E, Car PG et al. Molecular characterisation of JC virus strains detected in human brain tumours. Pathology 2003; 35(3):248–53.PubMedGoogle Scholar
  16. 16.
    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(13):7484–9.PubMedGoogle Scholar
  17. 17.
    Safak M, Khalili K. An overview: Human polyomavirus JC virus and its associated disorders. J Neurovirol 2003; 9(Suppl 1):3–9.PubMedGoogle Scholar
  18. 18.
    Corral I, Quereda C, Hellin T et al. Relapsing and remitting leukoencephalopathy associated with chronic HIV infection. Eur Neurol 2002; 48(1):39–41.PubMedGoogle Scholar
  19. 19.
    White FA, Ishaq M, Stoner GL et al. JC virus DNA is present in many human brain samples from patients without progressive multifocal leukoencephalopathy. J Virol 1992; 66(10):5726–34.PubMedGoogle Scholar
  20. 20.
    Joseph J, Major EO. Basic, clinical, and epidemiological studies of progressive multifocal leukoencephalopathy: Implications for therapy. J Neurovirol 2003; 9(Suppl 1):1–2.PubMedGoogle Scholar
  21. 21.
    Atwood WJ. Cellular receptors for the polyomaviruses. In: Khalili K, Stoner G, eds. Human Polyomaviruses: Molecular and Clinical Perspectives. New York: Wiley-Liss, 2001:53–72.Google Scholar
  22. 22.
    Mahmut S, Khalili K. An overview: Human polyomavirus JC virus and its associated disorders. J Neurovirol 2003; 9(Suppl 1):3–9.Google Scholar
  23. 23.
    Berger JR, Nath A. Clinical progressive multifocal leukoencephalopathy: Diagnosis and treatment. In: Khalili K, Stoner G, eds. Human Polyomaviruses: Molecular and Clinical Perspectives. New York: Wiley-Liss, 2001:237–56.Google Scholar
  24. 24.
    Koralnik IJ, Du Pasquier RA, Kuroda MJ et al. Association of prolonged survival in HLA-A2+ progressive multifocal leukoencephalopathy patients with a CTL response specific for a commonly recognized JC virus epitope. J Immunol 2002; 168(1):499–504.PubMedGoogle Scholar
  25. 25.
    Du Pasquier RA, Kuroda MJ, Schmitz JE et al. Low frequency of cytotoxic T lymphocytes against the novel HLA-A*0201-restricted JC virus epitope VP1(p36) in patients with proven or possible progressive multifocal leukoencephalopathy. J Virol 2003; 77(22):11918–26.PubMedGoogle Scholar
  26. 26.
    Clifford DB, Yiannoutsos C, Glicksman M et al. HAART improves prognosis in HIV-associated progressive multifocal leukoencephalopathy. Neurology 1999; 52(3):623–5.PubMedGoogle Scholar
  27. 27.
    Berger JR, Levy RM, Flomenhoft D et al. Predictive factors for prolonged survival in acquired immunodeficiency syndrome-associated progressive multifocal leukoencephalopathy. Ann Neurol 1998; 44(3):341–9.PubMedGoogle Scholar
  28. 28.
    Weber F, Goldmann C, Kramer M et al. Cellular and humoral immune response in progressive multifocal leukoencephalopathy. Ann Neurol 2001; 49(5):636–42.PubMedGoogle Scholar
  29. 29.
    Du Pasquier RA, Koralnik IJ. Inflammatory reaction in progressive multifocal leukoencephalopathy: Harmful or beneficial? J Neurovirol 2003; 9(Suppl 1):25–31.PubMedGoogle Scholar
  30. 30.
    Cinque P, Pierotti C, Vigano MG et al. The good and evil of HAART in HIV-related progressive multifocal leukoencephalopathy. J Neurovirol 2001; 7(4):358–63.PubMedGoogle Scholar
  31. 31.
    Cinque P, Bossolasco S, Brambilla AM et al. The effect of highly active antiretroviral theapy-induced immune reconstitution on development and outcome of progressive multifocal leukoencephalopathy: Study of 43 cases with reveiw of the literature. J Neurovirol 2003; 9(Suppl 1):73–80.PubMedGoogle Scholar
  32. 32.
    Berger JR, Concha M. Progressive multifocal leukoencephalopathy: The evolution of a disease once considered rare. J Neurovirol 1995; 1(1):5–18.PubMedGoogle Scholar
  33. 33.
    Berger JR. Progressive multifocal leukoencephalopathy in acquired immunodeficiency syndrome: Explaining the high incidence and disproportionate frequency of the illness relative to other immunosuppressive conditions. J Neurovirol 2003; 9(Suppl 1):38–41.PubMedGoogle Scholar
  34. 34.
    Berger JR, Chauhan A, Galey D et al. Epidemiological evidence and molecular basis of interactions between HIV and JC virus. J Neurovirol 2001; 7(4):329–38.PubMedGoogle Scholar
  35. 35.
    Seth P, Diaz F, Major EO. Advances in the biology of JC virus and induction of progressive multifocal leukoencephalopathy. J Neurovirol 2003; 9(2):236–46.PubMedGoogle Scholar
  36. 36.
    Royal W, Dupont B, McGuire D et al. Topotecan in the treatment of acquired immunodeficiency syndrome-related progressive multifocal leukoencephalopathy. J Neurovirol 2003; 9(3):411–9.PubMedGoogle Scholar
  37. 37.
    Marra CM, Rajicic N, Barker DE et al. A pilot study of cidofovir for progressive multifocal leukoencephalopathy in AIDS. Aids 2002; 16(13):1791–7.PubMedGoogle Scholar
  38. 38.
    Hall CD, Dafni U, Simpson D et al. Failure of cytarabine in progressive multifocal leukoencephalopathy associated with human immunodeficiency virus infection. AIDS Clinical Trials Group 243 Team. N Engl J Med 1998; 338(19):1345–51.PubMedGoogle Scholar
  39. 39.
    Geschwind MD, Skolasky RI, Royal WS et al. The relative contributions of HAART and alpha-interferon for therapy of progressive multifocal leukoencephalopathy in AIDS. J Neurovirol 2001; 7(4):353–7.PubMedGoogle Scholar
  40. 40.
    Gasnault J, Kousignian P, Kahraman M et al. Cidofovir in AIDS-associated progressive multifocal leukoencephalopathy: A monocenter observational study with clinical and JC virus load monitoring. J Neurovirol 2001; 7(4):375–81.PubMedGoogle Scholar
  41. 41.
    De Luca A, Giancola ML, Ammassari A et al. The effect of potent antiretroviral therapy and JC virus load in cerebrospinal fluid on clinical outcome of patients with AIDS-associated progressive multifocal leukoencephalopathy. J Infect Dis 2000; 182(4):1077–83.PubMedGoogle Scholar
  42. 42.
    De Luca A, Ammassari A, Cingolani A et al. Disease progression and poor survival of AIDS-associated progressive multifocal leukoencephalopathy despite highly active antiretroviral therapy. Aids 1998; 12(14):1937–8.PubMedGoogle Scholar
  43. 43.
    Cinque P, Koralnik IJ, Clifford DB. The evolving face of human immunodeficiency virus-related progressive multifocal leukoencephalopathy: Defining a consensus terminology. J Neurovirol 2003; 9(Suppl 1):88–92.PubMedGoogle Scholar
  44. 44.
    Yiannoutsos C, De Luca A. Designs for clinical trials to test the efficacy of therapeutics in progressive multifocal leukoencephalopathy. J Neurovirol 2001; 7:369–74.PubMedGoogle Scholar
  45. 45.
    Reploeg MD, Storch GA, Clifford DB. BK virus: A clinical review. Clin Infect Dis 2001; 33(2):191–202.PubMedGoogle Scholar
  46. 46.
    Hirsch HH, Mohaupt M, Klimkait T. Prospective monitoring of BK virus load after discontinuing sirolimus treatment in a renal transplant patient with BK virus nephropathy. J Infect Dis 2001; 184(11):1494–5, author reply 5–6.PubMedGoogle Scholar
  47. 47.
    Randhawa PS, Finkelstein S, Scantlebury V et al. Human polyoma virus-associated interstitial nephritis in the allograft kidney. Transplantation 1999; 67(1):103–9.PubMedGoogle Scholar
  48. 48.
    Haririan A, Klassen D. BK virus infection after nonrenal transplantation. Graft 2002; 5(Suppl):S58–S64.Google Scholar
  49. 49.
    Arthur RR, Shah KV, Baust SJ et al. Association of BK viruria with hemorrhagic cystitis in recipients of bone marrow transplants. N Engl J Med 1986; 315(4):230–4.PubMedGoogle Scholar
  50. 50.
    Leung AY, Mak R, Lie AK, et al. Clinicopathological features and risk factors of clinically overt haemorrhagic cystitis complicating bone marrow transplantation. Bone Marrow Transplant 2002; 29(6):509–13.PubMedGoogle Scholar
  51. 51.
    Gonzalez-Fraile MI, Canizo C, Caballero D, et al. Cidofovir treatment of human polyomavirus-associated acute haemorrhagic cystitis. Transpl Infect Dis 2001; 3(1):44–6.PubMedGoogle Scholar
  52. 52.
    Garderet L, Bittencourt H, Sebe P et al. Cystectomy for severe hemorrhagic cystitis in allogeneic stem cell transplant recipients. Transplantation 2000; 70(12):1807–11.PubMedGoogle Scholar
  53. 53.
    Kawakami M, Ueda S, Maeda T et al. Vidarabine therapy for virus-associated cystitis after allogeneic bone marrow transplantation. Bone Marrow Transplant 1997; 20(6):485–90.PubMedGoogle Scholar
  54. 54.
    Goddard AG, Saha V. Late-onset hemorrhagic cystitis following bone marrow transplantation: A case report. Pediatr Hematol Oncol 1997; 14(3):273–5.PubMedGoogle Scholar
  55. 55.
    Laszlo D, Bosi A, Guidi S et al. Prostaglandin E2 bladder instillation for the treatment of hemorrhagic cystitis after allogeneic bone marrow transplantation. Haematologica 1995; 80(5):421–5.PubMedGoogle Scholar
  56. 56.
    Randhawa P, Baksh F, Aoki N et al. JC virus infection in allograft kidneys: Analysis by polymerase chain reaction and immunohistochemistry. Transplantation 2001; 71(9):1300–3.PubMedGoogle Scholar
  57. 57.
    Li RM, Mannon RB, Kleiner D et al. BK virus and SV40 coinfection in polyomavirus nephropathy. Transplantation 2002; 74(11):1497–504.PubMedGoogle Scholar
  58. 58.
    Trofe J, Cavallo T, First MR et al. Polyomavirus in kidney and kidney-pancreas transplantation: A defined protocol for immunosuppression reduction and histologic monitoring. Transplant Proc 2002; 34(5):1788–9.PubMedGoogle Scholar
  59. 59.
    Randhawa PS, Demetris AJ. Nephropathy due to polyomavirus type BK. N Engl J Med 2000; 342(18):1361–3.PubMedGoogle Scholar
  60. 60.
    Trofe J, Gaber LW, Stratta RJ et al. Polyomavirus in kidney and kidney-pancreas transplant recipe ents. Transpl Infect Dis 2003; 5(1):21–8.PubMedGoogle Scholar
  61. 61.
    Ginevri F, De Santis R, Comoli P et al. Polyomavirus BK infection in pediatric kidney-allograft recipients: A single-center analysis of incidence, risk factors, and novel therapeutic approaches. Trans plantation 2003; 75(8):1266–70.Google Scholar
  62. 62.
    Howell DN, Smith SR, Butterly DW et al. Diagnosis and management of BK polyomavirus interstitial nephritis in renal transplant recipients. Transplantation 1999; 68(9):1279–88.PubMedGoogle Scholar
  63. 63.
    Binet I, Nickeleit V, Hirsch HH et al. Polyomavirus disease under new immunosuppressive drugs: A cause of renal graft dysfunction and graft loss. Transplantation 1999; 67(6):918–22.PubMedGoogle Scholar
  64. 64.
    Nickeleit V, Hirsch HH, Binet IF et al. Polyomavirus infection of renal allograft recipients: From latent infection to manifest disease. J Am Soc Nephrol 1999; 10(5):1080–9.PubMedGoogle Scholar
  65. 65.
    Nickeleit V, Hirsch HH, Zeiler M et al. BK-virus nephropathy in renal transplants-tubular necrosis, MHC-class II expression and rejection in a puzzling game. Nephrol Dial Transplant 2000; 15(3):324–32.PubMedGoogle Scholar
  66. 66.
    Nickeleit V, Klimkait T, Binet IF et al. Testing for polyomavirus type BK DNA in plasma to identify renal-allograft recipients with viral nephropathy. N Engl J Med 2000; 342(18):1309–15.PubMedGoogle Scholar
  67. 67.
    Binet I, Nickeleit V, Hirsch HH. Polyomavirus infections in transplant recipients. Current Opin ions in Organ Transplantation 2000; 5:210–16.Google Scholar
  68. 68.
    Ahuja M, Cohen EP, Dayer AM et al. Polyoma virus infection after renal transplantation. Use of immunostaining as a guide to diagnosis. Transplantation 2001; 71(7):896–9.PubMedGoogle Scholar
  69. 69.
    Barri YM, Ahmad I, Ketel BL et al. Polyoma viral infection in renal transplantation: The role of immunosuppressive therapy. Clin Transplant 2001; 15(4):240–6.PubMedGoogle Scholar
  70. 70.
    Buehrig CK, Lager DJ, Stegall MD et al. Influence of surveillance renal allograft biopsy on diagnosis and prognosis of polyomavirus-associated nephropathy. Kidney Int 2003; 64(2):665–73.PubMedGoogle Scholar
  71. 71.
    Poduval RD, Kadambi P, Javaid B et al. Leflunomide-a potential new therapeutic agent for BK nephropathy. Am J Transplant 2003; 3(Suppl 5):189, (Abstract 44).Google Scholar
  72. 72.
    Mengel M, Marwedel M, Radermacher J et al. Incidence of polyomavirus-nephropathy in renal allografts: Influence of modern immunosuppressive drugs. Nephrol Dial Transplant 2003; 18(6):1190–6.PubMedGoogle Scholar
  73. 73.
    Fishman JA. BK virus nephropathy—polyomavirus adding insult to injury. N Engl J Med 2002; 347(7):527–30.PubMedGoogle Scholar
  74. 74.
    Hirsch HH, Steiger J. Polyomavirus BK. The Lancet Infectious Diseases 2003; 3(10):611–23.PubMedGoogle Scholar
  75. 75.
    Kazory A, Ducloux D. Renal transplantation and polyomavirus infection: Recent clinical facts and controversies. Transpl Infect Dis 2003; 5(2):65–71.PubMedGoogle Scholar
  76. 76.
    Nickeleit V, Steiger J, Mihatsch MJ. BK virus infection after kidney transplantation. Graft 2002; 5(Suppl):S46–57.Google Scholar
  77. 77.
    Nickeleit V, Singh H, Mihatsch M. Polyomavirus nephropathy: Morphology, pathophysiology, and clinical management. Curr Opin Nephrol Hypertens 2003; 12(6):599–605.PubMedGoogle Scholar
  78. 78.
    Ramos E, Drachenberg CB, Papadimitriou JC et al. Clinical course of polyoma virus nephropathy in 67 renal transplant patients. J Am Soc Nephrol 2002; 13(8):2145–51.PubMedGoogle Scholar
  79. 79.
    Drachenberg RC, Drachenberg CB, Papadimitriou JC et al. Morphological spectrum of polyoma virus disease in renal allografts: Diagnostic accuracy of urine cytology. Am J Transplant 2001; 1(4):373–81.PubMedGoogle Scholar
  80. 80.
    Celik B, Shapiro R, Vats A et al. Polyomavirus allograft nephropathy: Sequential assessment of histologic viral load, tubulitis, and graft function following changes in immunosuppression. Am J Transplant 2003; 3(11):1378–82.PubMedGoogle Scholar
  81. 81.
    Drachenberg CB, Beskow CO, Cangro CB et al. Human polyoma virus in renal allograft biopsies: Morphological findings and correlation with urine cytology. Hum Pathol 1999; 30(8):970–7.PubMedGoogle Scholar
  82. 82.
    Hussain S, Bresnahan BA, Cohen EP et al. Rapid kidney allograft failure in patients with polyoma virus nephritis with prior treatment with antilymphocyte agents. Clin Transplant 2002; 16(1):43–7.PubMedGoogle Scholar
  83. 83.
    Hurault de Ligny B, Etienne I, Francois A et al. Polyomavirus-induced acute tubulo-interstitial nephritis in renal allograft recipients. Transplant Proc 2000; 32(8):2760–1.PubMedGoogle Scholar
  84. 84.
    Rahamimov R, Lustiga S, Tovar A et al. BK polyoma virus nephropathy in kidney transplant recipient: The role of new immunosuppressive agents. Transplant Proc 2003; 35(2):604–5.PubMedGoogle Scholar
  85. 85.
    Atwood WJ, Norkin LC. Class I major histocompatibility proteins as cell surface receptors for simian virus 40. J Virol 1989; 63(10):4474–7.PubMedGoogle Scholar
  86. 86.
    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(6):4643–9.PubMedGoogle Scholar
  87. 87.
    Liu CK, Hope AP, Atwood WJ. The human polyomavirus, JCV, does not share receptor specificity with SV40 on human glial cells. J Neurovirol 1998; 4(1):49–58.PubMedGoogle Scholar
  88. 88.
    Drachenberg CB, Papadimitriou JC, Wali R et al. BK polyoma virus allograft nephropathy: Ultrastructural features from viral cell entry to lysis. Am J Transplant 2003; 3(11):1383–92.PubMedGoogle Scholar
  89. 89.
    Schweighardt B, Atwood WJ. Virus receptors in the human central nervous system. J Neurovirol 2001; 7(3):187–95.PubMedGoogle Scholar
  90. 90.
    Atwood WJ. A combination of low-dose chlorpromazine and neutralizing antibodies inhibits the spread of JC virus (JCV) in a tissue culture model: Implications for prophylactic and therapeutic treatment of progressive multifocal leukencephalopathy. J Neurovirol 2001; 7(4):307–10.PubMedGoogle Scholar
  91. 91.
    Baum S, Ashok A, Gee G et al. Early events in the life cycle of JC virus as potential therapeutic targets for the treatment of progressive multifocal leukoencephalopathy. J Neurovirol 2003; 9(Suppl 1):32–7.PubMedGoogle Scholar
  92. 92.
    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(11):1825–34.PubMedGoogle Scholar
  93. 93.
    Chen Y, Norkin LC. Extracellular simian virus 40 transmits a signal that promotes virus enclosure within caveolae. Exp Cell Res 1999; 246(1):83–90.PubMedGoogle Scholar
  94. 94.
    Gilbert JM, Goldberg IG, Benjamin TL. Cell penetration and trafficking of polyomavirus. J Virol 2003; 77(4):2615–22.PubMedGoogle Scholar
  95. 95.
    Portolani M, Pietrosemoli P, Cermelli C et al. Suppression of BK virus replication and cytopathic effect by inhibitors of prokaryotic DNA gyrase. Antiviral Res 1988; 9(3):205–18.PubMedGoogle Scholar
  96. 96.
    Chen Y, Freund R, Listerud M et al. Retinoic acid inhibits transformation by preventing phosphatidylinositol 3-kinase dependent activation of the c-fos promoter. Oncogene 1999; 18(1):139–48.PubMedGoogle Scholar
  97. 97.
    Talmage DA, Listerud M. Retinoic acid suppresses polyoma virus transformation by inhibiting transcription of the c-fos proto-oncogene. Oncogene 1994; 9(12):3557–63.PubMedGoogle Scholar
  98. 98.
    Ferrazzi E, Peracchi M, Biasolo MA et al. Antiviral activity of gyrase inhibitors norfloxacin, coumermycin A1 and nalidixic acid. Biochem Pharmacol 1988; 37(9):1885–6.PubMedGoogle Scholar
  99. 99.
    Tarabek J, Zemla J, Bacik I. Northern blot hybridization analysis of polyoma virus-specific RNA synthesized under the block of virus replication by 5-bromo-2′-deoxyuridine. Acta Virol 1991; 35(4):305–12.PubMedGoogle Scholar
  100. 100.
    Andrei G, Snoeck R, Vandeputte M et al. Activities of various compounds against murine and primate polyomaviruses. Antimicrob Agents Chemother 1997; 41(3):587–93.PubMedGoogle Scholar
  101. 101.
    De Clercq E. Acyclic nucleoside phosphonates in the chemotherapy of DNA virus and retrovirus infections. Intervirology 1997; 40(5–6):295–303.PubMedGoogle Scholar
  102. 102.
    De Clercq E. In search of a selective antiviral chemotherapy. Clin Microbiol Rev 1997; 10(4):674–93.PubMedGoogle Scholar
  103. 103.
    Foster PF, Wright F, McLean D et al. Leflunomide administration as an adjunct in treatment of BK-polyoma viral disease in kidney allografts [abstract]. Am J Transplant 2003; 3(Suppl 5):421.Google Scholar
  104. 104.
    Snoeck R, Andrei G, Lilja H et al. Activity of malononitrilamide compounds against murine and simian polyomavirus. Geneva, Switzerland: Paper presented at: 5th International Conference on New Trends in Clinical and Experimental Immunosuppression 2002, [abstract].Google Scholar
  105. 105.
    Ma DD, Doan TL. Antisense oligonudeotide therapies: Are they the “magic bullets”? Ann Intern Med 1994; 120(2):161–3.PubMedGoogle Scholar
  106. 106.
    Levy RM, Ward S, Schalgeter K et al. Alternative delivery systems for antiviral nucleosides and antisense oligonucleotides to the brain. J Neurovirol 1997; 3(Suppl 1):S74–5.PubMedGoogle Scholar
  107. 107.
    Package insert. Vistide® (cidofovir injection). Foster City, CA: Gilead Sciences Inc., 2000.Google Scholar
  108. 108.
    Portilla J, Boix V, Roman F et al. Progressive multifocal leukoencephalopathy treated with cidofovir in HIV-infected patients receiving highly active anti-retroviral therapy. J Infect 2000; 41(2):182–4.PubMedGoogle Scholar
  109. 109.
    Cundy KC. Clinical pharmacokinetics of the antiviral nucleotide analogues cidofovir and adefovir. Clin Pharmacokinet 1999; 36(2):127–43.PubMedGoogle Scholar
  110. 110.
    Cassady KA, Whitley RJ. New therapeutic approaches to the alphaherpesvirus infections. J Antimicrob Chemother 1997; 39(2):119–28.PubMedGoogle Scholar
  111. 111.
    Package insert. Arava® Tablets (leflunomide). Kansas City, MO: Aventis Pharmaceuticals Inc., 2003.Google Scholar
  112. 112.
    Hou J, Major EO. The efficacy of nucleoside analogs against JC virus multiplication in a persis tently infected human fetal brain cell line. J Neurovirol 1998; 4(4):451–6.PubMedGoogle Scholar
  113. 113.
    Houston S, Roberts N, Mashinter L. Failure of cidofovir therapy in progressive multifocal leukoencephalopathy unrelated to human immunodeficiency virus. Clin Infect Dis 2001; 32(1):150–2.PubMedGoogle Scholar
  114. 114.
    Dodge RT. A case study: The use of cidofovir for the management of progressive multifocal leukoencephalopathy. J Assoc Nurses AIDS Care 1999; 10(4):70–4.PubMedGoogle Scholar
  115. 115.
    Cardenas RL, Cheng KH, Sack K. The effects of cidofovir on progressive multifocal leukoencephalopathy: An MRI case study. Neuroradiology 2001; 43(5):379–82.PubMedGoogle Scholar
  116. 116.
    Salmaggi A, Maccagnano E, Castagna A et al. Reversal of CSF positivity for JC virus genome by cidofovir in a patient with systemic lupus erythematosus and progressive multifocal leukoencephalopathy. Neurol Sci 2001; 22(1):17–20.PubMedGoogle Scholar
  117. 117.
    Razonablc RR, Aksamit AJ, Wright AJ et al. Cidofovir treatment of progressive multifocal leukoencephalopathy in a patient receiving highly active antiretroviral therapy. Mayo Clin Proc 2001; 76(11):1171–5.Google Scholar
  118. 118.
    Haider S, Nafziger D, Gutierrez JA et al. Progressive multifocal leukoencephalopathy and idiopathic CD4+lymphocytopenia: A case report and review of reported cases. Clin Infect Dis 2000; 31(4):E20–2.PubMedGoogle Scholar
  119. 119.
    Zimmermann T, Stingele K, Hartmann M et al. Successful treatment of aids related PML with HAART and cidofovir. Eur J Med Res 2001; 6(5):190–62.PubMedGoogle Scholar
  120. 120.
    Roberts MT, Carmichael A, Lever AM. Prolonged survival in AIDS-related progressive multifocal leucoencephalopathy following anti-retroviral therapy and cidofovir. Int J Antimicrob Agents 2003; 21(4):347–9.PubMedGoogle Scholar
  121. 121.
    Antinori A, Cingolani A, Lorenzini P et al. Clinical epidemiology and survival of progressive multifocal leukoencephalopathy in the era of highly active antiretroviral therapy: Data from the Italian Registry Investigative Neuro AIDS (IRINA). J Neurovirol 2003; 9(Suppl 1):47–53.PubMedGoogle Scholar
  122. 122.
    Kiewe P, Seyfert S, Korper S et al. Progressive multifocal leukoencephalopathy with detection of JC virus in a patient with chronic lymphocytic leukemia parallel to onset of fludarabine therapy. Leuk Lymphoma 2003; 44(10):1815–8.PubMedGoogle Scholar
  123. 123.
    De Luca A, Giancola ML, Ammassari A et al. Cidofovir added to HAART improves virological and clinical outcome in AIDS-associated progressive multifocal leukoencephalopathy. Aids 2000; 14(14):F117–21.PubMedGoogle Scholar
  124. 124.
    De Luca A, Giancola ML, Ammassari A et al. Potent anti-retroviral therapy with or without cidofovir for AIDS-associated progressive multifocal leukoencephalopathy: Extended follow-up of an observational study. J Neurovirol 2001; 7(4):364–8.PubMedGoogle Scholar
  125. 125.
    Taoufik Y, Delfraissy JF, Gasnault J. Highly active antiretroviral therapy does not improve survival of patients with high JC virus load in the cerebrospinal fluid at progressive multifocal leukoencephalopathy diagnosis. Aids 2000; 14(6):758–9.PubMedGoogle Scholar
  126. 126.
    Held TK, Biel SS, Nitsche A et al. Treatment of BK virus-associated hemorrhagic cystitis and simultaneous CMV reactivation with cidofovir. Bone Marrow Transplant 2000; 26(3):347–50.PubMedGoogle Scholar
  127. 127.
    Hatakeyama N, Suzuki N, Kudoh T et al. Successful cidofovir treatment of adenovirus-associated hemorrhagic cystitis and renal dysfunction after allogenic bone marrow transplant. Pediatr Infect Dis J 2003; 22(10):928–9.PubMedGoogle Scholar
  128. 128.
    Bjorang O, Tveitan H, Midtvedt K et al. Treatment of polyomavirus infection with cidofovir in a renal-transplant recipient. Nephrol Dial Transplant 2002; 17(11):2023–5.PubMedGoogle Scholar
  129. 129.
    Keller LS, Peh CA, Nolan J et al. BK transplant nephropathy successfully treated with cidofovir. Nephrol Dial Transplant 2003; 18(5):1013–4.PubMedGoogle Scholar
  130. 130.
    Kadambi PV, Josephson MA, Williams J et al. Treatment of refractory BK virus-associated nephropathy with cidofovir. Am J Transplant 2003; 3(2): 186–91.PubMedGoogle Scholar
  131. 131.
    Vats A, Shapiro R, Singh Randhawa P et al. Quantitative viral load monitoring and cidofovir therapy for the management of BK virus-associated nephropathy in children and adults. Transplantation 2003; 75(1):105–12.PubMedGoogle Scholar
  132. 132.
    Scantlebury V, Shapiro R, Randhawa P et al. Cidofovir: A method of treatment for BK virus-associated transplant nephropathy. Graft 2002; 5(Suppl):S82–7.Google Scholar
  133. 133.
    Mayer DF, Kushwaha SS. Transplant immunosuppressant agents and their role in autoimmune rheumatic diseases. Curr Opin Rheumatol 2003; 15(3):219–25.PubMedGoogle Scholar
  134. 134.
    Sanders S, Harisdangkul V. Leflunomide for the treatment of rheumatoid arthritis and autoimmunity. Am J Med Sci 2002; 323(4):190–3.PubMedGoogle Scholar
  135. 135.
    Goldenberg MM. Leflunomide, a novel immunomodulator for the treatment of active rheumatoid arthritis. Clin Ther 1999; 21(11):1837–52; discussion 21.PubMedGoogle Scholar
  136. 136.
    Lednicky JA, Stewart AR, Jenkins III JJ et al. SV40 DNA in human osteosarcomas shows sequence variation among T-antigen genes. Int J Cancer 1997; 72(5):791–800.PubMedGoogle Scholar
  137. 137.
    Waldman WJ, Knight DA, Blinder L et al. Inhibition of cytomegalovirus in vitro and in vivo by the experimental immunosuppressive agent leflunomide. Intervirology 1999; 42(5–6):412–8.PubMedGoogle Scholar
  138. 138.
    Waldman WJ, Knight DA, Lurain NS et al. Novel mechanism of inhibition of cytomegalovirus by the experimental immunosuppressive agent leflunomide. Transplantation 1999; 68(6):814–25.PubMedGoogle Scholar
  139. 139.
    Williams JW, Mital D, Chong A et al. Experiences with leflunomide in solid organ transplantation. Transplantation 2002; 73(3):358–66.PubMedGoogle Scholar
  140. 140.
    Kerr DA, Chang CF, Gordon J et al. Inhibition of human neurotropic virus (JCV) DNA replication in glial cells by camptothecin. Virology 1993; 196(2):612–8.PubMedGoogle Scholar
  141. 141.
    Package insert. Hycamtin® (topotecan hydrochloride). Research Triangle Park, North Carolina: GlaxoSmithKline Pharmaceuticals, 2003.Google Scholar
  142. 142.
    Rand KH, Johnson KP, Rubinstein LJ et al. Adenine arabinoside in the treatment of progressive multifocal leukoencephalopathy: Use of virus-containing cells in the urine to assess response to therapy. Ann Neurol 1977; 1(5):458–62.PubMedGoogle Scholar
  143. 143.
    Package Insert. Cytarabine. Irvine, California: GensiaSicor Pharmaceuticals, 1999.Google Scholar
  144. 144.
    Nicoli F, Chave B, Peragut JC et al. Efficacy of cytarabine in progressive multifocal leucoencephalopathy in AIDS. Lancet 1992; 339(8788):306.PubMedGoogle Scholar
  145. 145.
    O’Riordan T, Daly PA, Hutchinson M et al. Progressive multifocal leukoencephalopathy-remission with cytarabine. J Infect 1990; 20(1):51–4.PubMedGoogle Scholar
  146. 146.
    Steiger MJ, Tarnesby G, Gabe S et al. Successful outcome of progressive multifocal leukoencephalopathy with cytarabine and interferon. Ann Neurol 1993; 33(4):407–11.PubMedGoogle Scholar
  147. 147.
    Aksamit AJ. Treatment of nonAIDS progressive multifocal leukoencephaiopathy with cytosine arabinoside. J Neurovirol 2001; 7(4):386–90.PubMedGoogle Scholar
  148. 148.
    Levy RM, Major E, Ali MJ et al. Convection-enhanced intraparenchymal delivery (CEID) of cytosine arabinoside (AraC) for the treatment of HIV-related progressive multifocal leukoencephaiopathy (PML). J Neurovirol 2001; 7(4):382–5.PubMedGoogle Scholar
  149. 149.
    Hoffmann RP, Lewis IK. Vidarabine (Drug Evaluation). In: Hutchinson TA, Shahan DR, eds. DRUGDEX® System. MICROMEDEX, Greenwood Village, Colorado (Edition expires 9/2002).Google Scholar
  150. 150.
    Chapman C, Flower AJ, Durrant ST. The use of vidarabine in the treatment of human polyomavirus associated acute haemorrhagic cystitis. Bone Marrow Transplant 1991; 7(6):481–3.PubMedGoogle Scholar
  151. 151.
    Seabra C, Perez-Simon JA, Sierra M et al. Intra-muscular vidarabine therapy for polyomavirus-associated hemorrhagic cystitis following allogeneic hemopoietic stem cell transplantation. Bone Marrow Trans plant 2000; 26(11): 1229–30.Google Scholar
  152. 152.
    Vianelli N, Renga M, Azzi A et al. Sequential vidarabine infusion in the treatment of polyoma virus-associated acute haemorrhagic cystitis late after allogeneic bone marrow transplantation. Bone Marrow Transplant 2000; 25(3):319–20.PubMedGoogle Scholar
  153. 153.
    Puliyanda D, Amet N, Archana D et al. IVIG contains antibodies reactive with polyomaviruses BK and may represent a therapeutic option for BK virus and may represent a therapeutic option for BK nephropathy. Am J Transplant 2003; 3(Suppl 5):393 (Abstract 941).Google Scholar
  154. 154.
    Casadei DH, Rial MDC, Opelz G et al. A randomized and prospective study comparing treatment with high-dose intravenous immunoglobulin with monoclonal antibodies for rescue of kidney grafts with steroid-resistant rejection. Transplantation 2001; 71(1):53–8.PubMedGoogle Scholar
  155. 155.
    Cibrik DM, O Toole JF, Norman SP et al. IVIG for the treatment of BK nephropathy. Am J Transplant 2003; 3(Suppl 5):370 (Abstract 850).Google Scholar
  156. 156.
    Berger JR. Progressive Multifocal Leukoencephalopathy. Curr Treat Options Neurol 2000; 2(4):361–8.PubMedGoogle Scholar
  157. 157.
    Huang SS, Skolasky RL, Dal Pan GJ et al. Survival prolongation in HIV-associated progressive multifocal leukoencephalopathy treated with alpha-interferon: An observational study. J Neurovirol 1998; 4(3):324–32.PubMedGoogle Scholar
  158. 158.
    Clifford DB. Challenges for clinical trials to treat progressive multifocal leukoencephalopathy. J Neurovirol 2003; 9(Suppl 1):68–72.PubMedGoogle Scholar
  159. 159.
    Cheeseman SH, Black PH, Rubin RH et al. Interferon and BK Papovavirus—clinical and laboratory studies. J Infect Dis 1980; 141(2): 157–61.PubMedGoogle Scholar
  160. 160.
    Ramos E, Drachenberg CB, Portocarrero M et al. BK virus nephropathy diagnosis and treatment: Experience at the University of Maryland Renal Transplant Program. In: Cecka J, Terasaki P, eds. Clinical Transplants 2002. Los Angeles: UCLA Immunogenetics Center; 2003:143–53.Google Scholar
  161. 161.
    Mayr M, Nickeleit V, Hirsch HH et al. Polyomavirus BK nephropathy in a kidney transplant recipient: Critical issues of diagnosis and management. Am J Kidney Dis 2001; 38(3):E13.PubMedGoogle Scholar
  162. 162.
    Scantlebury V, Shapiro R, Justin G et al. Graft function after diagnosis of BK virus in adult kidney transplant recipients under tacrolimus-based immunosuppression [abstract]. Am J Transpl 2001; 1(Suppl 1):404.Google Scholar
  163. 163.
    Loertscher R, Suri R, Lipman M et al. Deliberate reduction of immunosuppression benefits patients with polyoma BK virus infection in kidney allografts [abstract]. Am J Transpl 2002; 2(Suppl 3):262.Google Scholar

Copyright information

© and Springer Science+Business Media 2006

Authors and Affiliations

  • Julie Roskopf
    • 1
  • Jennifer Trofe
    • 2
  • Robert J. Stratta
    • 1
  • Nasimul Ahsan
    • 3
  1. 1.Wake Forest University Baptist Medical CenterWinston-SalemUSA
  2. 2.Hospital of the University of PennsylvaniaPhiladelphiaUSA
  3. 3.Mayo Clinic Transplant CenterMayo Clinic - College of MedicineJacksonvilleUSA

Personalised recommendations