{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,17]],"date-time":"2025-11-17T05:49:09Z","timestamp":1763358549796},"reference-count":58,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2015,8,24]],"date-time":"2015-08-24T00:00:00Z","timestamp":1440374400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"NIH\/NIAID","award":["R01AI077460","P30MH092177"],"award-info":[{"award-number":["R01AI077460","P30MH092177"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal Cellular Physiology"],"published-print":{"date-parts":[[2015,12]]},"abstract":"<jats:sec><jats:label \/><jats:p>Progressive multifocal leukoencephalopathy (PML) is a severe demyelinating disease of the CNS caused by the human polyomavirus JC (JCV). JCV replication occurs only in human cells and investigation of PML has been severely hampered by the lack of an animal model. The common feature of PML is impairment of the immune system. The key to understanding PML is working out the complex mechanisms that underlie viral entry and replication within the CNS and the immunosurveillance that suppresses the virus or allows it to reactivate. Early models involved the simple inoculation of JCV into animals such as monkeys, hamsters, and mice. More recently, mouse models transgenic for the gene encoding the JCV early protein, T\u2010antigen, a protein thought to be involved in the disruption of myelin seen in PML, have been employed. These animal models resulted in tumorigenesis rather than demyelination. Another approach is to use animal polyomaviruses that are closely related to JCV but able to replicate in the animal such as mouse polyomavirus and SV40. More recently, novel models have been developed that involve the engraftment of human cells into the animal. Here, we review progress that has been made to establish an animal model for PML, the advances and limitations of different models and weigh future prospects. J. Cell. Physiol. 230: 2869\u20132874, 2015. \u00a9 2015 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcp.25047","type":"journal-article","created":{"date-parts":[[2015,6,3]],"date-time":"2015-06-03T11:48:13Z","timestamp":1433332093000},"page":"2869-2874","source":"Crossref","is-referenced-by-count":13,"title":["Animal Models for Progressive Multifocal Leukoencephalopathy"],"prefix":"10.1002","volume":"230","author":[{"given":"Martyn K.","family":"White","sequence":"first","affiliation":[{"name":"Department of Neuroscience, Center for Neurovirology Temple University School of Medicine Philadelphia Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennifer","family":"Gordon","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Center for Neurovirology Temple University School of Medicine Philadelphia Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joseph R.","family":"Berger","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Pennsylvania Perelman School of Medicine Philadelphia Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kamel","family":"Khalili","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Center for Neurovirology Temple University School of Medicine Philadelphia Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2015,8,24]]},"reference":[{"key":"e_1_2_3_2_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.36.4.499"},{"key":"e_1_2_3_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.abb.2015.02.033"},{"key":"e_1_2_3_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/81.1.93"},{"key":"e_1_2_3_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnen\/63.7.750"},{"key":"e_1_2_3_6_1","first-page":"39","article-title":"Transgenic mice expressing polyoma virus large T antigen in astrocytes develop severe dysmyelination of the central nervous system","volume":"66","author":"Baron\u2010Van Evercooren A","year":"1992","journal-title":"Lab Invest"},{"key":"e_1_2_3_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13365-013-0222-6"},{"key":"e_1_2_3_8_1","doi-asserted-by":"publisher","DOI":"10.3109\/13550289809113482"},{"key":"e_1_2_3_9_1","doi-asserted-by":"publisher","DOI":"10.2165\/11537510-000000000-00000"},{"key":"e_1_2_3_10_1","doi-asserted-by":"publisher","DOI":"10.3949\/ccjm.78.s2.03"},{"key":"e_1_2_3_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.23135"},{"key":"e_1_2_3_12_1","first-page":"6133","volume-title":"Fields virology, Sixth Edition","author":"DeCaprio JA","year":"2013"},{"key":"e_1_2_3_13_1","doi-asserted-by":"publisher","DOI":"10.2741\/1830"},{"key":"e_1_2_3_14_1","doi-asserted-by":"publisher","DOI":"10.1097\/NEN.0b013e318180e631"},{"key":"e_1_2_3_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awh215"},{"key":"e_1_2_3_16_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.84.11.3695"},{"key":"e_1_2_3_17_1","doi-asserted-by":"publisher","DOI":"10.1006\/viro.1994.1325"},{"key":"e_1_2_3_18_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI79186"},{"key":"e_1_2_3_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410320112"},{"key":"e_1_2_3_20_1","first-page":"223","article-title":"New world primates as a model of viral\u2010induced astrocytomas","volume":"105","author":"Houff SA","year":"1983","journal-title":"Prog Clin Biol Res"},{"key":"e_1_2_3_21_1","unstructured":"IARC Working Group on the Evaluation of Carcinogenic Risks to Humans.2012. 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