Polyomavirus-Associated Progressive Multifocal Leukoencephalopathy (PML) in HAART era

Document Type: Review Article


Department of Human Viral Vaccine, Razi Vaccine and Serum Research Institute, Karaj, Iran


Polyomaviruses may cause human disease, particularly in immunocompromised hosts. JCV, one of the members of polyomaviridae family, is the causative agent of the neurological disease progressive multifocal leukoencephalopathy (PML), which occurs mostly in immunocompromised patients. Progressive Multifocal leukoencephalopathy (PML) is a progressive demyelinating disorder of the central nervous system (CNS) resulting from infection of oligodendrocytes by JC polyomavirus. Whereas after highly active antiretroviral therapy (HAART), the incidence of nearly all of all neurological complication have decreased, this article evaluates the incidence and prognosis of JC polyomavirus-associated PML including a unchangeable incidence of PML associated with JC polyomavirus compared with other opportunistic disease and paradoxical results of disease remission in HAART era.


Main Subjects

Article Title [French]

La leucoencéphalopathie multifocale progressive (LEMP) associée au Polyomavirus à l’ère de l’HAART

Abstract [French]

Le polyomavirus peut affecter l’homme, particulièrement les individus immunodéprimés. Le JVC, l’un des membres de la famille des Polyomaviridae, est l’agent responsable d’une maladie neurologique, la leucoencéphalopathie multifocale progressive (LEMP). La LEMP est une maladie démyélinisante progressive du système nerveux central résultant de l’infection des oligodendrocytes par le polyomavirus JC. Il est avéré qu’après une thérapie antirétrovirale fortement active (HAART), l’incidence des complications neurologiques associées à cette infection diminue. Cette étude a pour objectif d’évaluer l’incidence et le pronostic médical de la LEMP causée par le polyomavirus JC en comparaison avec les résultats paradoxaux liés à la rémission d’autres maladies opportunistes suite à des traitements HAART.

Keywords [French]

  • Polyomavirus
  • JCV
  • LEMP
  • Epidemiologie
Abedi Kiasari, B., Vallely, P.J., Corless, C.E., Al-Hammadi, M., Klapper, P.E., 2008. Age-related pattern of KI and WU polyomavirus infection. J Clin Virol 43, 123-125.

Abedi Kiasari, B., Vallely, P.J., Klapper, P.E., 2011. Merkel cell polyomavirus DNA in immunocompetent and immunocompromised patients with respiratory disease. J Med Virol 83, 2220-2224.

Aksamit, A.J., Jr., 1995. Progressive multifocal leukoencephalopathy: a review of the pathology and pathogenesis. Microsc Res Tech 32, 302-311.

Albrecht, H., Hoffmann, C., Degen, O., Stoehr, A., Plettenberg, A., Mertenskotter, T., 1998. Highly active antiretroviral therapy significantly improves the prognosis of patients with HIV-associated progressive multifocal leukoencephalopathy. AIDS 12, 1149-1154.

Allander, T., Andreasson, K., Gupta, S., Bjerkner, A., Bogdanovic, G., Persson, M.A., Dalianis, T., Ramqvist, T., Andersson, B., 2007. Identification of a third human polyomavirus. J Virol 81, 4130-4136.

Antinori, A., Ammassari, A., Giancola, M.L., Cingolani, A., Grisetti, S., Murri, R., Alba, L., Ciancio, B., Soldani, F., Larussa, D., Ippolito, G., De Luca, A., 2001. Epidemiology and prognosis of AIDS-associated progressive multifocal leukoencephalopathy in the HAART era. J Neurovirol 7, 323-328.

Antinori, A., Cingolani, A., Lorenzini, P., Giancola, M.L., Uccella, I., Bossolasco, S., Grisetti, S., Moretti, F., Vigo, B., Bongiovanni, M., Del Grosso, B., Arcidiacono, M.I., Fibbia, G.C., Mena, M., Finazzi, M.G., Guaraldi, G., Ammassari, A., d'Arminio Monforte, A., Cinque, P., De Luca, A., Italian Registry Investigative Neuro, A.S.G., 2003. 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 9 Suppl 1, 47-53.

Asensi, V., Carton, J.A., Maradona, J.A., Ona, M., Melon, S., Martin-Roces, E.R., Asensi, J.M., Arribas, J.M., 1999. [Progressive multifocal leukoencephalopathy associated with human immunodeficiency virus infection: the clinical, neuroimaging, virological and evolutive characteristics in 35 patients]. Med Clin (Barc) 113, 210-214.

Astrom, K.E., Mancall, E.L., Richardson, E.P., Jr., 1958. Progressive multifocal leuko-encephalopathy; a hitherto unrecognized complication of chronic lymphatic leukaemia and Hodgkin's disease. Brain 81, 93-111.

Berenguer, J., Miralles, P., Arrizabalaga, J., Ribera, E., Dronda, F., Baraia-Etxaburu, J., Domingo, P., Marquez, M., Rodriguez-Arrondo, F.J., Laguna, F., Rubio, R., Lacruz Rodrigo, J., Mallolas, J., de Miguel, V., Group, G.S., 2003. Clinical course and prognostic factors of progressive multifocal leukoencephalopathy in patients treated with highly active antiretroviral therapy. Clin Infect Dis 36, 1047-1052.

Berger, J.R., 2000. Progressive Multifocal Leukoencephalopathy. Curr Treat Options Neurol 2, 361-368.

Berger, J.R., Concha, M., 1995. Progressive multifocal leukoencephalopathy: the evolution of a disease once considered rare. J Neurovirol 1, 5-18.

Berger, J.R., Houff, S., 2006. Progressive multifocal leukoencephalopathy: lessons from AIDS and natalizumab. Neurol Res 28, 299-305.

Berger, J.R., Major, E.O., 1999. Progressive multifocal leukoencephalopathy. Semin Neurol 19, 193-200.

Berger, J.R., Mucke, L., 1988. Prolonged survival and partial recovery in AIDS-associated progressive multifocal leukoencephalopathy. Neurology 38, 1060-1065.

Brooks, B.R., Walker, D.L., 1984. Progressive multifocal leukoencephalopathy. Neurol Clin 2, 299-313.

Casado, J.L., Corral, I., Garcia, J., Martinez-San Millan, J., Navas, E., Moreno, A., Moreno, S., 2014. Continued declining incidence and improved survival of progressive multifocal leukoencephalopathy in HIV/AIDS patients in the current era. Eur J Clin Microbiol Infect Dis 33, 179-187.

Cedeno-Laurent, F., Penalva de Oliveira, A.C., Vidal, J.E., Trujillo, J.R., 2011. Human Polyomavirus-Associated Cerebral Disorders in the Post-HAART Era. Patholog Res Int 2011, 562427.

Christensen, K.L., Holman, R.C., Hammett, T.A., Belay, E.D., Schonberger, L.B., 2010. Progressive multifocal leukoencephalopathy deaths in the USA, 1979-2005. Neuroepidemiology 35, 178-184.

Clifford, D.B., Yiannoutsos, C., Glicksman, M., Simpson, D.M., Singer, E.J., Piliero, P.J., Marra, C.M., Francis, G.S., McArthur, J.C., Tyler, K.L., Tselis, A.C., Hyslop, N.E., 1999. HAART improves prognosis in HIV-associated progressive multifocal leukoencephalopathy. Neurology 52, 623-625.

d'Arminio Monforte, A., Cinque, P., Mocroft, A., Goebel, F.D., Antunes, F., Katlama, C., Justesen, U.S., Vella, S., Kirk, O., Lundgren, J., Euro, S.S.G., 2004. Changing incidence of central nervous system diseases in the EuroSIDA cohort. Ann Neurol 55, 320-328.

d'Arminio Monforte, A., Cozzi-Lepri, A., Castagna, A., Antinori, A., De Luca, A., Mussini, C., Caputo, S.L., Arlotti, M., Magnani, G., Pellizzer, G., Maggiolo, F., Puoti, M., Icona Foundation Study, G., 2009. Risk of developing specific AIDS-defining illnesses in patients coinfected with HIV and hepatitis C virus with or without liver cirrhosis. Clin Infect Dis 49, 612-622.

Darbinyan, A., White, M.K., Akan, S., Radhakrishnan, S., Del Valle, L., Amini, S., Khalili, K., 2007. Alterations of DNA damage repair pathways resulting from JCV infection. Virology 364, 73-86.

De Luca, A., Ammassari, A., Cingolani, A., Giancola, M.L., Antinori, A., 1998. Disease progression and poor survival of AIDS-associated progressive multifocal leukoencephalopathy despite highly active antiretroviral therapy. AIDS 12, 1937-1938.

Di Giambenedetto, S., Vago, G., Pompucci, A., Scoppettuolo, G., Cingolani, A., Marzocchetti, A., Tumbarello, M., Cauda, R., De Luca, A., 2004. Fatal inflammatory AIDS-associated PML with high CD4 counts on HAART: a new clinical entity? Neurology 63, 2452-2453.

Dorries, K., 1984. Progressive multifocal leukoencephalopathy: analysis of JC virus DNA from brain and kidney tissue. Vir Res 1, 25-38.

Dorries, K., 2004. Human polyomaviruses, Wiley and Sons Ltd, England.

Dworkin, M.S., Wan, P.C., Hanson, D.L., Jones, J.L., 1999. Progressive multifocal leukoencephalopathy: improved survival of human immunodeficiency virus-infected patients in the protease inhibitor era. J Infect Dis 180, 621-625.

Dyrhol-Riise, A.M., Ohlsson, M., Skarstein, K., Nygaard, S.J., Olofsson, J., Jonsson, R., Asjo, B., 2001. T cell proliferation and apoptosis in HIV-1-infected lymphoid tissue: impact of highly active antiretroviral therapy. Clin Immunol 101, 180-191.

Engsig, F.N., Hansen, A.B., Omland, L.H., Kronborg, G., Gerstoft, J., Laursen, A.L., Pedersen, C., Mogensen, C.B., Nielsen, L., Obel, N., 2009. Incidence, clinical presentation, and outcome of progressive multifocal leukoencephalopathy in HIV-infected patients during the highly active antiretroviral therapy era: a nationwide cohort study. J Infect Dis 199, 77-83.

Ensoli, B., Barillari, G., Salahuddin, S.Z., Gallo, R.C., Wong-Staal, F., 1990. Tat protein of HIV-1 stimulates growth of cells derived from Kaposi's sarcoma lesions of AIDS patients. Nature 345, 84-86.

Falco, V., Olmo, M., del Saz, S.V., Guelar, A., Santos, J.R., Gutierrez, M., Colomer, D., Deig, E., Mateo, G., Montero, M., Pedrol, E., Podzamczer, D., Domingo, P., Llibre, J.M., 2008. Influence of HAART on the clinical course of HIV-1-infected patients with progressive multifocal leukoencephalopathy: results of an observational multicenter study. J Acquir Immune Defic Syndr 49, 26-31.

Feng, H., Shuda, M., Chang, Y., Moore, P.S., 2008. Clonal integration of a polyomavirus in human Merkel cell carcinoma. Science 319, 1096-1100.

Fong, I.W., Britton, C.B., Luinstra, K.E., Toma, E., Mahony, J.B., 1995. Diagnostic value of detecting JC virus DNA in cerebrospinal fluid of patients with progressive multifocal leukoencephalopathy. J Clin Microbiol 33, 484-486.

Frankel, A.D., Pabo, C.O., 1988. Cellular uptake of the tat protein from human immunodeficiency virus. Cell 55, 1189-1193.

Garvey, L., Winston, A., Walsh, J., Post, F., Porter, K., Gazzard, B., Fisher, M., Leen, C., Pillay, D., Hill, T., Johnson, M., Gilson, R., Anderson, J., Easterbrook, P., Bansi, L., Orkin, C., Ainsworth, J., Phillips, A.N., Sabin, C.A., 2011. HIV-associated central nervous system diseases in the recent combination antiretroviral therapy era. Eur J Neurol 18, 527-534.

Gasnault, J., Kahraman, M., de Goer de Herve, M.G., Durali, D., Delfraissy, J.F., Taoufik, Y., 2003. Critical role of JC virus-specific CD4 T-cell responses in preventing progressive multifocal leukoencephalopathy. AIDS 17, 1443-1449.

Gasnault, J., Taoufik, Y., Goujard, C., Kousignian, P., Abbed, K., Boue, F., 1999. Prolonged survival without neurological improvement in patients with AIDS-related progressive multifocal leukoencephalopathy on potent combined antiretroviral therapy. J Neurovirol 5, 421-429.

Gaynor, A.M., Nissen, M.D., Whiley, D.M., Mackay, I.M., Lambert, S.B., Wu, G., Brennan, D.C., Storch, G.A., Sloots, T.P., Wang, D., 2007. Identification of a novel polyomavirus from patients with acute respiratory tract infections. PLoS Pathog 3, e64.

Genis, P., Jett, M., Bernton, E.W., Boyle, T., Gelbard, H.A., Dzenko, K., Keane, R.W., Resnick, L., Mizrachi, Y., Volsky, D.J., et al., 1992. Cytokines and arachidonic metabolites produced during human immunodeficiency virus (HIV)-infected macrophage-astroglia interactions: implications for the neuropathogenesis of HIV disease. J Exp Med 176, 1703-1718.

Giancola, M.L., Rizzi, E.B., Lorenzini, P., Rovighi, L., Baldini, F., Schinina, V., Larussa, D., Bibbolino, C., Antinori, A., 2008. Progressive multifocal leukoencephalopathy in HIV-infected patients in the era of HAART: radiological features at diagnosis and follow-up and correlation with clinical variables. AIDS Res Hum Retroviruses 24, 155-162.

Gillespie, S.M., Chang, Y., Lemp, G., Arthur, R., Buchbinder, S., Steimle, A., Baumgartner, J., Rando, T., Neal, D., Rutherford, G., et al., 1991. Progressive multifocal leukoencephalopathy in persons infected with human immunodeficiency virus, San Francisco, 1981-1989. Ann Neurol 30, 597-604.

Giudici, B., Vaz, B., Bossolasco, S., Casari, S., Brambilla, A.M., Luke, W., Lazzarin, A., Weber, T., Cinque, P., 2000. Highly active antiretroviral therapy and progressive multifocal leukoencephalopathy: effects on cerebrospinal fluid markers of JC virus replication and immune response. Clin Infect Dis 30, 95-99.

Goh, S., Lindau, C., Tiveljung-Lindell, A., Allander, T., 2009. Merkel cell polyomavirus in respiratory tract secretions. Emerg Infect Dis 15, 489-491.

Gray, F., Bazille, C., Adle-Biassette, H., Mikol, J., Moulignier, A., Scaravilli, F., 2005. Central nervous system immune reconstitution disease in acquired immunodeficiency syndrome patients receiving highly active antiretroviral treatment. J Neurovirol 11 Suppl 3, 16-22.

Gray, F., Chretien, F., Vallat-Decouvelaere, A.V., Scaravilli, F., 2003. The changing pattern of HIV neuropathology in the HAART era. J Neuropathol Exp Neurol 62, 429-440.

Hirsch, H.H., Steiger, J., 2003. Polyomavirus BK. Lancet Infect Dis 3, 611-623.

Holman, R.C., Janssen, R.S., Buehler, J.W., Zelasky, M.T., Hooper, W.C., 1991. Epidemiology of progressive multifocal leukoencephalopathy in the United States: analysis of national mortality and AIDS surveillance data. Neurology 41, 1733-1736.

Inui, K., Miyagawa, H., Sashihara, J., Miyoshi, H., Tanaka-Taya, K., Nishigaki, T., Teraoka, S., Mano, T., Ono, J., Okada, S., 1999. Remission of progressive multifocal leukoencephalopathy following highly active antiretroviral therapy in a patient with HIV infection. Brain Dev 21, 416-419.

Jellinger, K.A., Setinek, U., Drlicek, M., Bohm, G., Steurer, A., Lintner, F., 2000. Neuropathology and general autopsy findings in AIDS during the last 15 years. Acta Neuropathol 100, 213-220.

Kepes, J.J., Chou, S.M., Price, L.W., Jr., 1975. Progressive multifocal leukoencephalopathy with 10-year survival in a patient with nontropical sprue. Report of a case with unusual light and electron microscopic features. Neurology 25, 1006-1012.

Keramer, C., Evers, S., Nolting, T., Arendt, G., Husstedt, I.W., 2008. Cidofovir in combination with  HAART and suvival AIDS- associated  progressive multifocal leukoencephalopathy. J Neurol Neurosurg Psychiatry 255, 526-531.

Kleinschmidt-DeMasters, B.K., Tyler, K.L., 2005. Progressive multifocal leukoencephalopathy complicating treatment with natalizumab and interferon beta-1a for multiple sclerosis. N Engl J Med 353, 369-374.

Krupp, L.B., Lipton, R.B., Swerdlow, M.L., Leeds, N.E., Llena, J., 1985. Progressive multifocal leukoencephalopathy: clinical and radiographic features. Ann Neurol 17, 344-349.

Ledergerber, B., Egger, M., Erard, V., Weber, R., Hirschel, B., Furrer, H., Battegay, M., Vernazza, P., Bernasconi, E., Opravil, M., Kaufmann, D., Sudre, P., Francioli, P., Telenti, A., 1999. AIDS-related opportunistic illnesses occurring after initiation of potent antiretroviral therapy: the Swiss HIV Cohort Study. JAMA 282, 2220-2226.

Lednicky, J.A., Stewart, A.R., Jenkins, J.J., Finegold, M.J., Butel, J.S., 1997. SV40 DNA in human osteosarcomas shows sequence variation among T-antigen genes. Int J Cancer 72, 791-800.

Ledoux, S., Libman, I., Robert, F., Just, N., 1989. Progressive multifocal leukoencephalopathy with gray matter involvement. Can J Neurol Sci 16, 200-202.

Lima, M.A., Bernal-Cano, F., Clifford, D.B., Gandhi, R.T., Koralnik, I.J., 2010. Clinical outcome of long-term survivors of progressive multifocal leukoencephalopathy. J Neurol Neurosurg Psychiatry 81, 1288-1291.

Lima, M.A., Drislane, F.W., J., K.I., 2006. Seizures and their outcome in progressive multifocal leukoencephalopathy. Neurology 66, 262-264.

Major, E.O., Amemiya, K., Tornatore, C.S., Houff, S.A., Berger, J.R., 1992. Pathogenesis and molecular biology of progressive multifocal leukoencephalopathy, the JC virus-induced demyelinating disease of the human brain. Clin Microbiol Rev 5, 49-73.

Malhotra, A., Sidhu, R., 2006. Progressive multifocal leukoencephalopathy. Eur J Radiol 57, 35-39.

Manley, K., O'Hara, B.A., Gee, G.V., Simkevich, C.P., Sedivy, J.M., Atwood, W.J., 2006. NFAT4 is required for JC virus infection of glial cells. J Virol 80, 12079-12085.

Martinez, A.J., Sell, M., Mitrovics, T., Stoltenburg-Didinger, G., Iglesias-Rozas, J.R., Giraldo-Velasquez, M.A., Gosztonyi, G., Schneider, V., Cervos-Navarro, J., 1995. The neuropathology and epidemiology of AIDS. A Berlin experience. A review of 200 cases. Pathol Res Pract 191, 427-443.

Martinez, J.V., Mazziotti, J.V., Efron, E.D., Bonardo, P., Jordan, R., Sevlever, G., Martinez, M., Verbanaz, S.C., Salazar, Z.S., Pardal, M.F., Reisin, R., 2006. Immune reconstitution inflammatory syndrome associated with PML in AIDS: a treatable disorder. Neurology 67, 1692-1694.

Masliah, E., DeTeresa, R.M., Mallory, M.E., Hansen, L.A., 2000. Changes in pathological findings at autopsy in AIDS cases for the last 15 years. AIDS 14, 69-74.

Messam, C.A., Hou, J., Gronostajski, R.M., Major, E.O., 2003. Lineage pathway of human brain progenitor cells identified by JC virus susceptibility. Ann Neurol 53, 636-646.

Miralles, P., Berenguer, J., Garcia de Viedma, D., Padilla, B., Cosin, J., Lopez-Bernaldo de Quiros, J.C., Munoz, L., Moreno, S., Bouza, E., 1998. Treatment of AIDS-associated progressive multifocal leukoencephalopathy with highly active antiretroviral therapy. AIDS 12, 2467-2472.

Miralles, P., Berenguer, J., Lacruz, C., Cosin, J., Lopez, J.C., Padilla, B., Munoz, L., Garcia-de-Viedma, D., 2001. Inflammatory reactions in progressive multifocal leukoencephalopathy after highly active antiretroviral therapy. AIDS 15, 1900-1902.

Monaco, M.C., Atwood, W.J., Gravell, M., Tornatore, C.S., Major, E.O., 1996. JC virus infection of hematopoietic progenitor cells, primary B lymphocytes, and tonsillar stromal cells: implications for viral latency. J Virol 70, 7004-7012.

Monaco, M.C., Jensen, P.N., Hou, J., Durham, L.C., Major, E.O., 1998. Detection of JC virus DNA in human tonsil tissue: evidence for site of initial viral infection. J Virol 72, 9918-9923.

Padgett, B.L., Walker, D.L., ZuRhein, G.M., Eckroade, R.J., Dessel, B.H., 1971. Cultivation of papova-like virus from human brain with progressive multifocal leucoencephalopathy. Lancet 1, 1257-1260.

Persidsky, Y., Ghorpade, A., Rasmussen, J., Limoges, J., Liu, X.J., Stins, M., 1999. Microglial and astrocyte chemokines regulate monocyte migration through the blood-brain barrier in human immunodeficiency virus-1 encephalitis. Ame J Pathol 155, 1599-1611.

Petito, C.K., Cho, E.S., Lemann, W., Navia, B.A., Price, R.W., 1986. Neuropathology of acquired immunodeficiency syndrome (AIDS): an autopsy review. J Neuropathol Exp Neurol 45, 635-646.

Portilla, J., Boix, V., Roman, F., Reus, S., Merino, E., 2000. Progressive multifocal leukoencephalopathy treated with cidofovir in HIV-infected patients receiving highly active anti-retroviral therapy. J Infect 41, 182-184.

Ransohoff, R.M., 2005. Natalizumab and PML. Nat Neurosci 8, 1275.

Sabath, B.F., Major, E.O., 2002. Traffic of JC virus from sites of initial infection to the brain: the path to progressive multifocal leukoencephalopathy. J Infect Dis 186 Suppl 2, S180-186.

Sacktor, N., McDermott, M.P., Marder, K., Schifitto, G., Selnes, O.A., McArthur, J.C., 2002. HIV-associated cognitive impairment before and after the advent of combination therapy. J Neurovirol 8, 136-142.

Safdar, A., Rubocki, R.J., Horvath, J.A., Narayan, K.K., Waldron, R.L., 2002. Fatal immune restoration disease in human immunodeficiency virus type 1-infected patients with progressive multifocal leukoencephalopathy: impact of antiretroviral therapy-associated immune reconstitution. Clin Infect Dis 35, 1250-1257.

Seth, P., Diaz, F., Major, E.O., 2003. Advances in the biology of JC virus and induction of progressive multifocal leukoencephalopathy. J Neurovirol 9, 236-246.

Shah, K.V., 1996. Polyomaviruses, Lippincott-Raven publishers, Philadelphia.

Stankoff, B., Tourbah, A., Suarez, S., Turell, E., Stievenart, J.L., Payan, C., Coutellier, A., Herson, S., Baril, L., Bricaire, F., Calvez, V., Cabanis, E.A., Lacomblez, L., Lubetzki, C., 2001. Clinical and spectroscopic improvement in HIV-associated cognitive impairment. Neurology 56, 112-115.

Tassie, J.M., Gasnault, J., Bentata, M., Deloumeaux, J., Boue, F., Billaud, E., Costagliola, D., 1999. Survival improvement of AIDS-related progressive multifocal leukoencephalopathy in the era of protease inhibitors. Clinical Epidemiology Group. French Hospital Database on HIV. AIDS 13, 1881-1887.

Tyler, K.L., 2003. The uninvited guest: JC virus infection of neurons in PML. Neurology 61, 734-735.

Van Assche, G., Van Ranst, M., Sciot, R., Dubois, B., Vermeire, S., Noman, M., Verbeeck, J., Geboes, K., Robberecht, W., Rutgeerts, P., 2005. Progressive multifocal leukoencephalopathy after natalizumab therapy for Crohn's disease. N Engl J Med 353, 362-368.

Vendrely, A., Bienvenu, B., Gasnault, J., Thiebault, J.B., Salmon, D., Gray, F., 2005. Ulminant inflammatory leukoencephalopathy associated with HAART-induced immune restoration in AIDS-related progressive multifocal leukoencephalopathy. Acta Neuropathol 109, 449-455.

von Einsiedel, R.W., Samorei, I.W., Pawlita, M., Zwissler, B., Deubel, M., Vinters, H.V., 2004. New JC virus infection patterns by in situ polymerase chain reaction in brains of acquired immunodeficiency syndrome patients with progressive multifocal leukoencephalopathy. J Neurovirol 10, 1-11.

Weber, T., Weber, F., Petry, H., Luke, W., 2001. Immune response in progressive multifocal leukoencephalopathy: an overview. J Neurovirol 7, 311-317.

Wyen, C., Hoffmann, C., Schmeisser, N., Wohrmann,


Qurishi, A., Rockstroh, N., Esser, J., S., et al., 2004. Progressive multifocal leukencephalopathy in patients on highly  active antiretroviral therapy: survival and risk factors  of death. J Acquir Immune Defic Syndr 37, 1263-1268.

Yoganathan, K., Brown, D., Yoganathan, K., 2012. Remission of progressive multifocal leukoencephalopathy following highly active antiretroviral therapy in a man with AIDS. Int J Gen Med 5, 331-334.

Yogo, Y., Matsushima-Ohno, T., Hayashi, T., Sugimoto, C., Sakurai, M., Kanazawa, I., 2001. JC virus regulatory region rearrangements in the brain of a long surviving patient with progressive multifocal leukoencephalopathy. J Neurol Neurosurg Psychiatry 71, 397-400.

Yoritaka, A., Ohta, K., Kishida, S., 2007. Prevalence of neurological complications in Japanese patients with AIDS after the introduction of HAART. Rinsho Shinkeigaku 47, 491-496.

Yousry, T.A., Major, E.O., Ryschkewitsch, C., Fahle, G., Fischer, S., Hou, J., Curfman, B., Miszkiel, K., Mueller-Lenke, N., Sanchez, E., Barkhof, F., Radue, E.W., Jager, H.R., Clifford, D.B., 2006. Evaluation of patients treated with natalizumab for progressive multifocal leukoencephalopathy. N Engl J Med 354, 924-933.

Zu, Rhein, G., Chou, S.M., 1965. Particles resembling papovaviruses in human cerebral demyelinating disease. Science 148, 1477-1479.