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Clinical and Developmental Immunology
Volume 2013 (2013), Article ID 839719, 17 pages
http://dx.doi.org/10.1155/2013/839719
Review Article

New Insights on Human Polyomavirus JC and Pathogenesis of Progressive Multifocal Leukoencephalopathy

1Department of Public Health and Infectious Diseases, “Sapienza” University of Rome, P.le Aldo Moro, 5-00185 Rome, Italy
2Department of Public Health and Infectious Diseases, Institute Pasteur, Cenci-Bolognetti Foundation, “Sapienza” University of Rome, P.le Aldo Moro, 5-00185 Rome, Italy
3San Raffaele Pisana Scientific Institute for Research, Hospitalization and Health Care, Via Val Cannuta, 247-00166 Rome, Italy
4Sbarro Institute for Cancer Research and Molecular Medicine, Center for Biotechnology, College of Science and Technology, Temple University, 1900 N. 12th Street, Philadelphia, PA 19122, USA

Received 7 January 2013; Accepted 6 March 2013

Academic Editor: Serena Delbue

Copyright © 2013 Anna Bellizzi et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. B. L. Padgett, D. L. Walker, G. M. ZuRhein, R. J. Eckroade, and B. H. Dessel, “Cultivation of papova-like virus from human brain with progressive multifocal leucoencephalopathy,” The Lancet, vol. 1, no. 7712, pp. 1257–1260, 1971. View at Scopus
  2. K. E. Åström, E. L. Mancall, and E. P. Richardson Jr., “Progressive multifocal leuko-encephalopathy, a hitherto unrecognized complication of chronic lymphatic leukaemia and Hodgkin’s disease,” Brain, vol. 81, no. 1, pp. 93–111, 1958. View at Publisher · View at Google Scholar
  3. B. J. Brew, N. W. S. Davies, P. Cinque, D. B. Clifford, and A. Nath, “Progressive multifocal leukoencephalopathy and other forms of JC virus disease,” Nature Reviews Neurology, vol. 6, no. 12, pp. 667–679, 2010. View at Publisher · View at Google Scholar · View at Scopus
  4. A. Bellizzi, C. Nardis, E. Anzivino et al., “Human polyomavirus JC reactivation and pathogenetic mechanisms of progressive multifocal leukoencephalopathy and cancer in the era of monoclonal antibody therapies,” Journal of Neurovirology, vol. 18, no. 1, pp. 1–11, 2012. View at Publisher · View at Google Scholar
  5. L. Del Valle and K. Khalili, “Detection of human polyomavirus proteins, T-antigen and agnoprotein, in human tumor tissue arrays,” Journal of Medical Virology, vol. 82, no. 5, pp. 806–811, 2010. View at Publisher · View at Google Scholar · View at Scopus
  6. C. S. Tan and I. J. Koralnik, “Progressive multifocal leukoencephalopathy and other disorders caused by JC virus: clinical features and pathogenesis,” The Lancet Neurology, vol. 9, no. 4, pp. 425–437, 2010. View at Publisher · View at Google Scholar · View at Scopus
  7. R. Weissert, “Progressive multifocal leukoencephalopathy,” Journal of Neuroimmunology, vol. 231, no. 1-2, pp. 73–77, 2011. View at Publisher · View at Google Scholar · View at Scopus
  8. E. O. Major, “Progressive multifocal leukoencephalopathy in patients on immunomodulatory therapies,” Annual Review of Medicine, vol. 61, pp. 35–47, 2010. View at Publisher · View at Google Scholar · View at Scopus
  9. Y. Orba, T. Suzuki, Y. Makino et al., “Large T antigen promotes JC virus replication in G2-arrested cells by inducing ATM- and ATR-mediated G2 checkpoint signaling,” Journal of Biological Chemistry, vol. 285, no. 2, pp. 1544–1554, 2010. View at Publisher · View at Google Scholar · View at Scopus
  10. L. Del Valle, J. Gordon, M. Assimakopoulou 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 Research, vol. 61, no. 10, pp. 4287–4293, 2001. View at Scopus
  11. B. Bollag, L. H. Kilpatrick, S. K. Tyagarajan, M. J. Tevethia, and R. J. Frisque, “JC virus T′135, T′136 and T′165 proteins interact with cellular p107 and p130 in vivo and influence viral transformation potential,” Journal of NeuroVirology, vol. 12, no. 6, pp. 428–442, 2006. View at Publisher · View at Google Scholar · View at Scopus
  12. B. Bollag, C. A. Hofstetter, M. M. Reviriego-Mendoza, and R. J. Frisque, “JC virus small T antigen binds phosphatase PP2A and Rb family proteins and is required for efficient viral DNA replication activity,” PloS one, vol. 5, no. 5, Article ID e10606, 2010. View at Publisher · View at Google Scholar · View at Scopus
  13. T. Suzuki, Y. Orba, Y. Okada et al., “The human polyoma JC virus agnoprotein acts as a viroporin,” PLoS Pathogens, vol. 6, no. 3, Article ID e1000801, 2010. View at Publisher · View at Google Scholar · View at Scopus
  14. V. Pietropaolo, M. Videtta, D. Fioriti et al., “Rearrangement patterns of JC virus noncoding control region from different biological samples,” Journal of NeuroVirology, vol. 9, no. 6, pp. 603–611, 2003. View at Scopus
  15. M. Mischitelli, D. Fioriti, M. Videtta et al., “Investigation on the role of cell transcriptional factor Sp1 and HIV-1 TAT protein in PML onset or development,” Journal of Cellular Physiology, vol. 204, no. 3, pp. 913–918, 2005. View at Publisher · View at Google Scholar · View at Scopus
  16. L. J. Marshall and E. O. Major, “Molecular regulation of JC virus tropism: insights into potential therapeutic targets for progressive multifocal leukoencephalopathy,” Journal of Neuroimmune Pharmacology, vol. 5, no. 3, pp. 404–417, 2010. View at Publisher · View at Google Scholar · View at Scopus
  17. R. J. Frisque, “Nucleotide sequence of the region encompassing the JC virus origin of DNA replication,” Journal of Virology, vol. 46, no. 1, pp. 170–176, 1983. View at Scopus
  18. M. K. White, M. Safak, and K. Khalili, “Regulation of gene expression in primate polyomaviruses,” Journal of Virology, vol. 83, no. 21, pp. 10846–10856, 2009. View at Publisher · View at Google Scholar · View at Scopus
  19. M. J. Wortman, C. P. Krachmarov, J. H. Kim et al., “Interaction of HIV-1 Tat with purα in nuclei of human glial cells: characterization of RNA-mediated protein-protein binding,” Journal of Cellular Biochemistry, vol. 77, no. 1, pp. 65–74, 2000.
  20. D. C. Daniel, M. J. Wortman, R. J. Schiller et al., “Coordinate effects of human immunodeficiency virus type 1 protein Tat and cellular protein Purα on DNA replication initiated at the JC virus origin,” Journal of General Virology, vol. 82, no. 7, pp. 1543–1553, 2001. View at Scopus
  21. M. J. D. Post, C. Yiannoutsos, D. Simpson et al., “Progressive multifocal leukoencephalopathy in AIDS: are there any MR findings useful to patient management and predictive of patient survival?” American Journal of Neuroradiology, vol. 20, no. 10, pp. 1896–1906, 1999.
  22. M. M. Thurnher, M. J. D. Post, A. Rieger, C. Kleibl-Popov, C. Loewe, and E. Schindler, “Initial and follow-up MR imaging findings in AIDS-related progressive multifocal leukoencephalopathy treated with highly active antiretroviral therapy,” American Journal of Neuroradiology, vol. 22, no. 5, pp. 977–984, 2001. View at Scopus
  23. E. O. Major and G. S. Ault, “Progressive multifocal leukoencephalopathy: clinical and laboratory observations on a viral induced demyelinating disease in the immunodeficient patient,” Current Opinion in Neurology, vol. 8, no. 3, pp. 184–190, 1995. View at Scopus
  24. K. L. Tyler, “Emerging viral infections of the central nervous system: part 2,” Archives of Neurology, vol. 66, no. 9, pp. 1065–1074, 2009. View at Publisher · View at Google Scholar
  25. M. C. G. Monaco, P. N. Jensen, J. Hou, L. C. Durham, and E. O. Major, “Detection of JC virus DNA in human tonsil tissue: evidence for site of initial viral infection,” Journal of Virology, vol. 72, no. 12, pp. 9918–9923, 1998. View at Scopus
  26. M. L. Chapagain and V. R. Nerurkar, “Human polyomavirus JC (JCV) infection of luman B lymphocytes: a possible mechanism for JCV transmigration across the blood-brain barrier,” Journal of Infectious Diseases, vol. 202, no. 2, pp. 184–191, 2010. View at Publisher · View at Google Scholar · View at Scopus
  27. M. Jiang, J. R. Abend, S. F. Johnson, and M. J. Imperiale, “The role of polyomaviruses in human disease,” Virology, vol. 384, no. 2, pp. 266–273, 2009. View at Publisher · View at Google Scholar · View at Scopus
  28. M. K. White and K. Khalili, “Pathogenesis of progressive multifocal leukoencephalopathy—revisited,” Journal of Infectious Diseases, vol. 203, no. 5, pp. 578–586, 2011. View at Publisher · View at Google Scholar · View at Scopus
  29. K. Manley, B. A. O'Hara, G. V. Gee, C. P. Simkevich, J. M. Sedivy, and W. J. Atwood, “NFAT4 is required for JC virus infection of glial cells,” Journal of Virology, vol. 80, no. 24, pp. 12079–12085, 2006. View at Publisher · View at Google Scholar · View at Scopus
  30. H. S. Wollebo, M. Safak, L. Del Valle, K. Khalili, and M. K. White, “Role for tumor necrosis factor-alpha in JC virus reactivation and progressive multifocal leukoencephalopathy,” Journal of Neuroimmunology, vol. 233, no. 1-2, pp. 46–53, 2011. View at Publisher · View at Google Scholar · View at Scopus
  31. L. Romagnoli, H. S. Wollebo, S. L. Deshmane et al., “Modulation of JC virus transcription by C/EBPβ,” Virus Research, vol. 146, no. 1-2, pp. 97–106, 2009. View at Publisher · View at Google Scholar
  32. S. Ghosh and M. Karin, “Missing pieces in the NF-kappaB puzzle,” Cell, vol. 109, supplement, pp. S81–S96, 2002.
  33. D. P. Ramji and P. Foka, “CCAAT/enhancer-binding proteins: structure, function and regulation,” The Biochemical Journal, vol. 365, no. 3, pp. 561–575, 2002.
  34. B. Hu, Z. Wu, H. Jin, N. Hashimoto, T. Liu, and S. H. Phan, “CCAAT/enhancerbinding protein beta isoforms and the regulation of alpha-smooth muscle actin gene expression by IL-1 beta,” The Journal of Immunology, vol. 173, no. 7, pp. 4661–4668, 2004.
  35. G. Perez-Liz, L. Del Valle, A. Gentilella, S. Croul, and K. Khalili, “Detection of JC virus DNA fragments but not proteins in normal brain tissue,” Annals of Neurology, vol. 64, no. 4, pp. 379–387, 2008. View at Publisher · View at Google Scholar · View at Scopus
  36. H. Mitoma, T. Horiuchi, N. Hatta et al., “Infliximab induces potent anti-inflammatory responses by outside-to-inside signals through transmembrane TNF-α,” Gastroenterology, vol. 128, no. 2, pp. 376–392, 2005. View at Publisher · View at Google Scholar · View at Scopus
  37. S. Ho, N. Clipstone, L. Timmermann et al., “The mechanism of action of cyclosporin A and FK506,” Clinical Immunology and Immunopathology, vol. 80, no. 3, pp. S40–S45, 1996. View at Publisher · View at Google Scholar · View at Scopus
  38. A. Bellizzi, E. Anzivino, F. Ferrari et al., “Polyomavirus JC reactivation and noncoding control region sequence analysis in pediatric Crohn's disease patients treated with infliximab,” Journal of NeuroVirology, vol. 17, no. 4, pp. 303–313, 2011. View at Publisher · View at Google Scholar
  39. R. L. P. Lindberg, L. Achtnichts, F. Hoffmann, J. Kuhle, and L. Kappos, “Natalizumab alters transcriptional expression profiles of blood cell subpopulations of multiple sclerosis patients,” Journal of Neuroimmunology, vol. 194, no. 1-2, pp. 153–164, 2008. View at Publisher · View at Google Scholar · View at Scopus
  40. S. Gallant and G. Gilkeson, “ETS transcription factors and regulation of immunity,” Archivum Immunologiae et Therapiae Experimentalis, vol. 54, no. 3, pp. 149–163, 2006. View at Publisher · View at Google Scholar · View at Scopus
  41. H. Schmidlin, S. A. Diehl, M. Nagasawa et al., “Spi-B inhibits human plasma cell differentiation by repressing BLIMP1 and XBP-1 expression,” Blood, vol. 112, no. 5, pp. 1804–1812, 2008. View at Publisher · View at Google Scholar · View at Scopus
  42. L. Del Valle, M. K. White, and K. Khalili, “Potential mechanisms of the human polyomavirus JC in neural oncogenesis,” Journal of Neuropathology and Experimental Neurology, vol. 67, no. 8, pp. 729–740, 2008. View at Publisher · View at Google Scholar · View at Scopus
  43. M. A. Lima, A. Marzocchetti, P. Autissier et al., “Frequency and phenotype of JC virus-specific CD8+ T lymphocytes in the peripheral blood of patients with progressive multifocal leukoencephalopathy,” Journal of Virology, vol. 81, no. 8, pp. 3361–3368, 2007. View at Publisher · View at Google Scholar
  44. B. L. Padgett and D. L. Walker, “Prevalence of antibodies in human sera against JC virus, an isolate from a case of progressive multifocal leukoencephalopathy,” Journal of Infectious Diseases, vol. 127, no. 4, pp. 467–470, 1973. View at Scopus
  45. J. M. Kean, S. Rao, M. Wang, and R. L. Garcea, “Seroepidemiology of human polyomaviruses,” PLoS Pathogens, vol. 5, no. 3, Article ID e1000363, 2009. View at Publisher · View at Google Scholar · View at Scopus
  46. F. Weber, C. Goldmann, M. Krämer et al., “Cellular and humoral immune response in progressive multifocal leukoencephalopathy,” Annals of Neurology, vol. 49, no. 5, pp. 636–642, 2001. View at Publisher · View at Google Scholar
  47. S. A. Houff and J. R. Berger, “The bone marrow, B cells, and JC virus,” Journal of Neurovirology, vol. 14, no. 5, pp. 341–343, 2008. View at Publisher · View at Google Scholar
  48. M. A. Lima, F. Bernal-Cano, D. B. Clifford, R. T. Gandhi, and I. J. Koralnik, “Clinical outcome of long-term survivors of progressive multifocal leukoencephalopathy,” Journal of Neurology, Neurosurgery and Psychiatry, vol. 81, no. 11, pp. 1288–1291, 2010. View at Publisher · View at Google Scholar · View at Scopus
  49. C. Wüthrich, S. Kesari, W. K. Kim et al., “Characterization of lymphocytic infiltrates in progressive multifocal leukoencephalopathy: co-localization of CD8+T cells with JCV-infected glial cells,” Journal of NeuroVirology, vol. 12, no. 2, pp. 116–128, 2006. View at Publisher · View at Google Scholar · View at Scopus
  50. M. Matloubian, R. J. Concepcion, and R. Ahmed, “CD4+ T cells are required to sustain CD8+ cytotoxic T-cell responses during chronic viral infection,” Journal of Virology, vol. 68, no. 12, pp. 8056–8063, 1994. View at Scopus
  51. J. R. Berger and S. Houff, “Progressive multifocal leukoencephalopathy: lessons from AIDS and natalizumab,” Neurological Research, vol. 28, no. 3, pp. 299–305, 2006. View at Publisher · View at Google Scholar · View at Scopus
  52. C. C. Carter, A. Onafuwa-Nuga, L. A. McNamara et al., “HIV-1 infects multipotent progenitor cells causing cell death and establishing latent cellular reservoirs,” Nature Medicine, vol. 16, no. 4, pp. 446–451, 2010. View at Publisher · View at Google Scholar · View at Scopus
  53. M. W. Ferenczy, L. J. Marshall, C. D. S. Nelson, W. J. Atwood, A. Nath, and K. Khalili, “Molecular biology, epidemiology, and pathogenesis of progressive multifocal leukoencephalopathy, the JC virus-induced demyelinating disease of the human brain,” Clinical Microbiology Reviews, vol. 25, no. 3, pp. 471–506, 2012. View at Publisher · View at Google Scholar
  54. D. C. Daniel, Y. Kinoshita, M. A. Khan et al., “Internalization of exogenous human immunodeficiency virus-1 protein, Tat, by KG-1 oligodendroglioma cells followed by stimulation of DNA replication initiated at the JC virus origin,” DNA and Cell Biology, vol. 23, no. 12, pp. 858–867, 2004. View at Publisher · View at Google Scholar · View at Scopus
  55. S. Nukuzuma, K. Nakamichi, M. Kameoka et al., “Efficient propagation of progressive multifocal leukoencephalopathy-type JC virus in COS-7-derived cell lines stably expressing Tat protein of human immunodeficiency virus type 1,” Microbiology and Immunology, vol. 54, no. 12, pp. 758–762, 2010. View at Publisher · View at Google Scholar · View at Scopus
  56. M. R. Stettner, J. A. Nance, C. A. Wright et al., “SMAD proteins of oligodendroglial cells regulate transcription of JC virus early and late genes coordinately with the Tat protein of human immunodeficiency virus type 1,” Journal of General Virology, vol. 90, no. 8, pp. 2005–2014, 2009. View at Publisher · View at Google Scholar · View at Scopus
  57. M. C. G. Monaco, B. F. Sabath, L. C. Durham, and E. O. Major, “JC virus multiplication in human hematopoietic progenitor cells requires the NF-1 class D transcription factor,” Journal of Virology, vol. 75, no. 20, pp. 9687–9695, 2001. View at Publisher · View at Google Scholar · View at Scopus
  58. M. K. White, E. M. Johnson, and K. Khalili, “Multiple roles for Puralpha in cellular and viral regulation,” Cell Cycle, vol. 8, no. 3, pp. 1–7, 2009. View at Scopus
  59. H. Wang, M. K. White, R. Kaminski et al., “Role of Purα in the modulation of homologous recombination-directed DNA repair by HIV-1 Tat,” Anticancer Research, vol. 28, no. 3 A, pp. 1441–1447, 2008.
  60. J. R. Berger, A. Chauhan, D. Galey, and A. Nath, “Epidemiological evidence and molecular basis of interactions between HIV and JC virus,” Journal of NeuroVirology, vol. 7, no. 4, pp. 329–338, 2001. View at Publisher · View at Google Scholar · View at Scopus
  61. T. Johnson and A. Nath, “Immune reconstitution inflammatory syndrome and the central nervous system,” Current Opinion in Neurology, vol. 24, no. 3, pp. 284–290, 2011. View at Publisher · View at Google Scholar · View at Scopus
  62. F. Gray, C. Bazille, H. Adle-Biassette, J. Mikol, A. Moulignier, and F. Scaravilli, “Central nervous system immune reconstitution disease in acquired immunodeficiency syndrome patients receiving highly active antiretroviral treatment,” Journal of NeuroVirology, vol. 11, no. 3, pp. 16–22, 2005. View at Publisher · View at Google Scholar · View at Scopus
  63. A. Marzocchetti, M. Lima, T. Tompkins et al., “Efficient in vitro expansion of JC virus-specific CD8+ T-cell responses by JCV peptide-stimulated dendritic cells from patients with progressive multifocal leukoencephalopathy,” Virology, vol. 383, no. 2, pp. 173–177, 2009. View at Publisher · View at Google Scholar · View at Scopus
  64. K. R. Carson, D. Focosi, E. O. Major et al., “Monoclonal antibody-associated progressive multifocal leucoencephalopathy in patients treated with rituximab, natalizumab, and efalizumab: a review from the Research on Adverse Drug Events and Reports (RADAR) project,” The Lancet Oncology, vol. 10, no. 8, pp. 816–824, 2009. View at Publisher · View at Google Scholar · View at Scopus
  65. D. L. Keene, C. Legare, E. Taylor, J. Gallivan, G. M. Cawthorn, and D. Vu, “Monoclonal antibodies and progressive multifocal leukoencephalopathy,” The Canadian Journal of Neurological Sciences, vol. 38, no. 4, pp. 565–571, 2011.
  66. R. G. R. Edula and M. F. Picco, “An evidence-based review of natalizumab therapy in the management of Crohn's disease,” Therapeutics and Clinical Risk Management, vol. 5, no. 1, pp. 935–942, 2009. View at Scopus
  67. F. Neumann, F. Zohren, and R. Haas, “The role of natalizumab in hematopoietic stem cell mobilization,” Expert Opinion on Biological Therapy, vol. 9, no. 8, pp. 1099–1106, 2009. View at Publisher · View at Google Scholar · View at Scopus
  68. M. Krumbholz, I. Meinl, T. Kümpfel, R. Hohlfeld, and E. Meinl, “Natalizumab disproportionately increases circulating pre-B and B cells in multiple sclerosis,” Neurology, vol. 71, no. 17, pp. 1350–1354, 2008. View at Publisher · View at Google Scholar · View at Scopus
  69. L. J. Marshall, L. Dunham, and E. O. Major, “Transcription factor Spi-B binds unique sequences present in the tandem repeat promoter/enhancer of JC virus and supports viral activity,” The Journal of General Virology, vol. 91, no. 12, pp. 3042–3052, 2010. View at Publisher · View at Google Scholar
  70. C. Warnke, V. Smolianov, T. Dehmel et al., “CD34+ progenitor cells mobilized by natalizumab are not a relevant reservoir for JC virus,” Multiple Sclerosis, vol. 17, no. 2, pp. 151–156, 2011. View at Publisher · View at Google Scholar
  71. A. P. Lysandropoulos and R. A. Du Pasquier, “Demyelination as a complication of new immunomodulatory treatments,” Current Opinion in Neurology, vol. 23, no. 3, pp. 226–233, 2010. View at Publisher · View at Google Scholar · View at Scopus
  72. D. B. Clifford, A. DeLuca, D. M. Simpson, G. Arendt, G. Giovannoni, and A. Nath, “Natalizumab-associated progressive multifocal leukoencephalopathy in patients with multiple sclerosis: lessons from 28 cases,” The Lancet Neurology, vol. 9, no. 4, pp. 438–446, 2010. View at Publisher · View at Google Scholar · View at Scopus
  73. I. L. Tan, J. C. McArthur, D. B. Clifford, E. O. Major, and A. Nath, “Immune reconstitution inflammatory syndrome in natalizumab-associated PML,” Neurology, vol. 77, no. 11, pp. 1061–1067, 2011.
  74. A. H. Cross, J. L. Stark, J. Lauber, M. J. Ramsbottom, and J. A. Lyons, “Rituximab reduces B cells and T cells in cerebrospinal fluid of multiple sclerosis patients,” Journal of Neuroimmunology, vol. 180, no. 1-2, pp. 63–70, 2006. View at Publisher · View at Google Scholar · View at Scopus
  75. E. Guttman-Yassky, Y. Vugmeyster, M. A. Lowes et al., “Blockade of CD11a by efalizumab in psoriasis patients induces a unique state of T-cell hyporesponsiveness,” Journal of Investigative Dermatology, vol. 128, no. 5, pp. 1182–1191, 2008. View at Publisher · View at Google Scholar · View at Scopus
  76. M. Lebwohl, S. K. Tyring, T. K. Hamilton et al., “A novel targeted t-cell modulator, efalizumab, for plaque psoriasis,” The New England Journal of Medicine, vol. 349, no. 21, pp. 2004–2013, 2003. View at Publisher · View at Google Scholar · View at Scopus
  77. J. G. Krueger, H. D. Ochs, P. Patel, E. Gilkerson, E. Guttman-Yassky, and W. Dummer, “Effect of therapeutic integrin (CD11a) blockade with efalizumab on immune responses to model antigens in humans: results of a randomized, single blind study,” Journal of Investigative Dermatology, vol. 128, no. 11, pp. 2615–2624, 2008. View at Publisher · View at Google Scholar · View at Scopus
  78. J. R. Berger, “Progressive multifocal leukoencephalopathy and newer biological agents,” Drug Safety, vol. 33, no. 11, pp. 969–983, 2010.
  79. D. Kumar, T. W. Bouldin, and R. G. Berger, “A case of progressive multifocal leukoencephalopathy in a patient treated with infliximab,” Arthritis and Rheumatism, vol. 62, no. 11, pp. 3191–3195, 2010. View at Publisher · View at Google Scholar · View at Scopus
  80. A. B. Gottlieb, F. Chamian, S. Masud et al., “TNF inhibition rapidly down-regulates multiple proinflammatory pathways in psoriasis plaques,” Journal of Immunology, vol. 175, no. 4, pp. 2721–2729, 2005. View at Scopus
  81. J. M. H. Van den Brande, H. Braat, G. R. Van den Brink et al., “Infliximab but not etanercept induces apoptosis in lamina propria T-lymphocytes from patients with Crohn's disease,” Gastroenterology, vol. 124, no. 7, pp. 1774–1785, 2003. View at Publisher · View at Google Scholar · View at Scopus
  82. A. Bellizzi, V. Barucca, D. Fioriti et al., “Early years of biological agents therapy in Crohn's disease and risk of the human polyomavirus JC reactivation,” Journal of Cellular Physiology, vol. 224, no. 2, pp. 316–326, 2010. View at Publisher · View at Google Scholar · View at Scopus
  83. M. Ramos-Casals, Roberto-Perez-Alvarez, C. Diaz-Lagares, M. J. Cuadrado, and M. A. Khamashta, “Autoimmune diseases induced by biological agents. A double-edged sword?” Autoimmunity Reviews, vol. 9, no. 3, pp. 188–193, 2010. View at Publisher · View at Google Scholar · View at Scopus
  84. E. O. Major, A. E. Miller, P. Mourrain, R. G. Traub, E. de Widt, and J. Sever, “Establishment of a line of human fetal glial cells that supports JC virus multiplication,” Proceedings of the National Academy of Sciences of the United States of America, vol. 82, no. 4, pp. 1257–1261, 1985.
  85. L. Feigenbaum, K. Khalili, E. Major, and G. Khoury, “Regulation of the host range of human papovavirus JCV,” Proceedings of the National Academy of Sciences of the United States of America, vol. 84, no. 11, pp. 3695–3698, 1987. View at Scopus
  86. K. Amemiya, R. Traub, L. Durham, and E. O. Major, “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,” Journal of Biological Chemistry, vol. 267, no. 20, pp. 14204–14211, 1992. View at Scopus
  87. V. Ravichandran and E. O. Major, “DNA-binding transcription factor NF-1A negatively regulates JC virus multiplication,” The Journal of General Virology, vol. 89, no. 6, pp. 1396–1401, 2008.
  88. T. Shinohara, K. Nagashima, and E. O. Major, “Propagation of the human polyomavirus, JCV, in human neuroblastoma cell lines,” Virology, vol. 228, no. 2, pp. 269–277, 1997. View at Publisher · View at Google Scholar · View at Scopus
  89. R. Gosert, P. Kardas, E. O. Major, and H. H. Hirsch, “Rearranged JC virus noncoding control regions found in progressive multifocal leukoencephalopathy patient samples increase virus early gene expression and replication rate,” Journal of Virology, vol. 84, no. 20, pp. 10448–10456, 2010. View at Publisher · View at Google Scholar · View at Scopus
  90. M. Wegner, D. W. Drolet, and M. G. Rosenfeld, “Regulation of JC virus by the POU-domain transcription factor Tst-1: implications for progressive multifocal leukoencephalopathy,” Proceedings of the National Academy of Sciences of the United States of America, vol. 90, no. 10, pp. 4743–4747, 1993. View at Scopus
  91. N. N. Chen and K. Khalili, “Transcriptional regulation of human JC polyomavirus promoters by cellular proteins YB-1 and Pur α in glial cells,” Journal of Virology, vol. 69, no. 9, pp. 5843–5848, 1995. View at Scopus
  92. C. Y. Shivakumar and G. C. Das, “Biochemical and mutational analysis of the polyomavirus core promoter: involvement of nuclear factor-1 in early promoter function,” Journal of General Virology, vol. 75, no. 6, pp. 1281–1290, 1994. View at Scopus
  93. Y. Yogo, T. Kitamura, C. Sugimoto et al., “Isolation of a possible archetypal JC virus DNA sequence from nonimmunocompromised individuals,” Journal of Virology, vol. 64, no. 6, pp. 3139–3143, 1990.
  94. G. S. Ault, “Activity of JC virus archetype and PML-type regulatory regions in glial cells,” Journal of General Virology, vol. 78, no. 1, pp. 163–169, 1997. View at Scopus
  95. V. Ravichandran, B. F. Sabath, P. N. Jensen, S. A. Houff, and E. O. Major, “Interactions between c-Jun, nuclear factor 1, and JC virus promoter sequences: implications for viral tropism,” Journal of Virology, vol. 80, no. 21, pp. 10506–10513, 2006. View at Publisher · View at Google Scholar · View at Scopus
  96. M. Safak, G. L. Gallia, and K. Khalili, “A 23-bp sequence element from human neurotropic JC virus is responsive to NF-κB subunits,” Virology, vol. 262, no. 1, pp. 178–189, 1999. View at Publisher · View at Google Scholar · View at Scopus
  97. K. U. Kumar, L. R. Devireddy, S. C. Tang, A. Pater, and M. M. Pater, “Human JC virus nuclear factor 1 binding motifs and large tumor antigen region required for transactivation of late promoter,” Journal of Neurochemistry, vol. 67, no. 2, pp. 473–481, 1996. View at Scopus
  98. M. Safak, G. L. Gallia, and K. Khalili, “Reciprocal interaction between two cellular proteins, Purα and YB-1, modulates transcriptional activity of JCV(CY) in glial cells,” Molecular and Cellular Biology, vol. 19, no. 4, pp. 2712–2723, 1999. View at Scopus
  99. M. Safak and K. Khalili, “Physical and functional interaction between viral and cellular proteins modulate JCV gene transcription,” Journal of NeuroVirology, vol. 7, no. 4, pp. 288–292, 2001. View at Publisher · View at Google Scholar · View at Scopus
  100. H. S. Kim, N. M. Goncalves, and J. W. Henson, “Glial cell-specific regulation of the JC virus early promoter by large T antigen,” Journal of Virology, vol. 74, no. 2, pp. 755–763, 2000. View at Publisher · View at Google Scholar · View at Scopus
  101. P. Shrikant and E. N. Benveniste, “The central nervous system as an immunocompetent organ: role of glial cells in antigen presentation,” Journal of Immunology, vol. 157, no. 5, pp. 1819–1822, 1996. View at Scopus
  102. K. E. Malone, S. A. Stohlman, C. Ramakrishna, W. Macklin, and C. C. Bergmann, “Induction of class I antigen processing components in oligodendroglia and microglia during viral encephalomyelitis,” GLIA, vol. 56, no. 4, pp. 426–435, 2008. View at Publisher · View at Google Scholar · View at Scopus
  103. C. L. Mack, C. L. Vanderlugt-Castaneda, K. L. Neville, and S. D. Miller, “Microglia are activated to become competent antigen presenting and effector cells in the inflammatory environment of the Theiler's virus model of multiple sclerosis,” Journal of Neuroimmunology, vol. 144, no. 1-2, pp. 68–79, 2003. View at Publisher · View at Google Scholar · View at Scopus
  104. S. S. Ousman and P. Kubes, “Immune surveillance in the central nervous system,” Nature Neuroscience, vol. 15, no. 8, pp. 1096–1101, 2012.
  105. R. M. Ransohoff, P. Kivisäkk, and G. Kidd, “Three or more routes for leukocyte migration into the central nervous system,” Nature Reviews Immunology, vol. 3, no. 7, pp. 569–581, 2003. View at Publisher · View at Google Scholar
  106. C. Loeffler, K. Dietz, A. Schleich et al., “Immune surveillance of the normal human CNS takes place in dependence of the locoregional blood-brain barrier configuration and is mainly performed by CD3+/CD8+ lymphocytes,” Neuropathology, vol. 31, no. 3, pp. 230–238, 2011. View at Publisher · View at Google Scholar · View at Scopus
  107. M. Laschinger, P. Vajkoczy, and B. Engelhardt, “Encephalitogenic T cells use LFA-1 for transendothelial migration but not during capture and initial adhesion strengthening in healthy spinal cord microvessels in vivo,” European Journal of Immunology, vol. 32, no. 12, pp. 3598–3606, 2002.
  108. R. Mukerjee, B. E. Sawaya, K. Khalili, and S. Amini, “Association of p65 and C/EBPβ with HIV-1 LTR modulates transcription of the viral promoter,” Journal of Cellular Biochemistry, vol. 100, no. 5, pp. 1210–1216, 2007. View at Publisher · View at Google Scholar · View at Scopus
  109. T. S. Gorrill and K. Khalili, “Cooperative interaction of p65 and C/EBPβ modulates transcription of BKV early promoter,” Virology, vol. 335, no. 1, pp. 1–9, 2005. View at Publisher · View at Google Scholar · View at Scopus
  110. I. Nagano, S. Nakamura, M. Yoshioka, J. Onodera, K. Kogure, and Y. Itoyama, “Expression of cytokines in brain lesions in subacute sclerosing panencephalitis,” Neurology, vol. 44, no. 4, pp. 710–715, 1994. View at Scopus
  111. N. Ishida, K. Hayashi, M. Hoshijima et al., “Large scale gene expression analysis of osteoclastogenesis in vitro and elucidation of NFAT2 as a key regulator,” Journal of Biological Chemistry, vol. 277, no. 43, pp. 41147–41156, 2002. View at Publisher · View at Google Scholar · View at Scopus
  112. A. Marzocchetti, C. Wuthrich, C. S. Tan et al., “Rearrangement of the JC virus regulatory region sequence in the bone marrow of a patient with rheumatoid arthritis and progressive multifocal leukoencephalopathy,” Journal of NeuroVirology, vol. 14, no. 5, pp. 455–458, 2008. View at Publisher · View at Google Scholar · View at Scopus
  113. C. S. Tan, B. J. Dezube, P. Bhargava et al., “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,” Journal of Infectious Diseases, vol. 199, no. 6, pp. 881–888, 2009. View at Publisher · View at Google Scholar · View at Scopus
  114. A. Darbinyan, M. K. White, S. Akan et al., “Alterations of DNA damage repair pathways resulting from JCV infection,” Virology, vol. 364, no. 1, pp. 73–86, 2007. View at Publisher · View at Google Scholar · View at Scopus
  115. E. Sock, J. Enderich, and M. Wegner, “The J domain of papovaviral large tumor antigen is required for synergistic interaction with the POU-domain protein Tst-1/Oct6/SCIP,” Molecular and Cellular Biology, vol. 19, no. 4, pp. 2455–2464, 1999. View at Scopus
  116. K. Hara, C. Sugimoto, T. Kitamura, N. Aoki, F. Taguchi, and Y. Yogo, “Archetype JC virus efficiently replicates in COS-7 cells, simian cells constitutively expressing simian virus 40 T antigen,” Journal of Virology, vol. 72, no. 7, pp. 5335–5342, 1998. View at Scopus
  117. P. N. Jensen and E. O. Major, “A classification scheme for human polyomavirus JCV variants based on the nucleotide sequence of the noncoding regulatory region,” Journal of NeuroVirology, vol. 7, no. 4, pp. 280–287, 2001. View at Publisher · View at Google Scholar · View at Scopus
  118. H. T. Agostini, C. F. Ryschkewitsch, and G. L. Stoner, “Rearrangements of archetypal regulatory regions in JC virus genomes from urine,” Research in Virology, vol. 149, no. 3, pp. 163–170, 1998. View at Publisher · View at Google Scholar · View at Scopus
  119. S. Delbue, G. Sotgiu, D. Fumagalli et al., “A case of a progressive multifocal leukoencephalopathy patient with four different JC virus transcriptional control region rearrangements in cerebrospinal fluid, blood, serum, and urine,” Journal of NeuroVirology, vol. 11, no. 1, pp. 51–57, 2005. View at Publisher · View at Google Scholar · View at Scopus
  120. C. E. Reid, H. Li, G. Sur et al., “Sequencing and analysis of JC virus DNA from natalizumab-treated PML patients,” Journal of Infectious Diseases, vol. 204, no. 2, pp. 237–244, 2011. View at Publisher · View at Google Scholar
  121. L. J. Marshall, L. D. Moore, M. M. Mirsky, and E. O. Major, “JC virus promoter/enhancers contain TATA box-associated Spi-B-binding sites that support early viral gene expression in primary astrocytes,” The Journal of General Virology, vol. 93, no. 3, pp. 651–661, 2011.
  122. D. Roux, M. A. Bouldouyre, S. Mercier-Delarue et al., “JC virus variant associated with cerebellar atrophy in a patient with AIDS,” Journal of Clinical Microbiology, vol. 49, no. 6, pp. 2196–2199, 2011. View at Publisher · View at Google Scholar · View at Scopus
  123. N. Sidhu and J. A. McCutchan, “Unmasking of PML by HAART: unusual clinical features and the role of IRIS,” Journal of Neuroimmunology, vol. 219, no. 1-2, pp. 100–104, 2010. View at Publisher · View at Google Scholar · View at Scopus
  124. M. L. Chapagain, S. Verma, F. Mercier, R. Yanagihara, and V. R. Nerurkar, “Polyomavirus JC infects human brain microvascular endothelial cells independent of serotonin receptor 2A,” Virology, vol. 364, no. 1, pp. 55–63, 2007. View at Publisher · View at Google Scholar · View at Scopus