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Here we show that a large percentage of IL-12 transgenic mice developed severe ataxia within 5 to 10 weeks after infection with BDV. By contrast, no disease developed in mock-infected IL-12 transgenic and wild-type mice until 4 months of age. Neurological symptoms were rare in infected wild-type animals, and if they occurred, these were milder and appeared later. Histological analyses showed that the cerebellum of infected IL-12 transgenic mice, which is the brain region with strongest transgene expression, contained large numbers of CD4<jats:sup>+<\/jats:sup>and CD8<jats:sup>+<\/jats:sup>T cells as well as lower numbers of B cells, whereas other parts of the CNS showed only mild infiltration by lymphocytes. The cerebellum of diseased mice further showed severe astrogliosis, calcifications and signs of neurodegeneration. BDV antigen and nucleic acids were present in lower amounts in the inflamed cerebellum of infected transgenic mice than in the noninflamed cerebellum of infected wild-type littermates, suggesting that IL-12 or IL-12-induced cytokines exhibited antiviral activity. We propose that BDV infection accelerates the frequency by which immune cells such as lymphocytes and NK cells enter the CNS and then respond to IL-12 present in the local milieu causing disease. Our results illustrate that infection of the CNS with a virus that is benign in certain hosts can be harmful in such normally disease-resistant hosts if the tissue is unfavorably preconditioned by proinflammatory cytokines.<\/jats:p>","DOI":"10.1128\/jvi.76.23.12223-12232.2002","type":"journal-article","created":{"date-parts":[[2002,11,1]],"date-time":"2002-11-01T19:04:50Z","timestamp":1036177490000},"page":"12223-12232","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":20,"title":["Borna Disease Virus Accelerates Inflammation and Disease Associated with Transgenic Expression of Interleukin-12 in the Central Nervous System"],"prefix":"10.1128","volume":"76","author":[{"given":"Susanna","family":"Freude","sequence":"first","affiliation":[{"name":"Abteilung Neuropathologie, Pathologisches Institut, Universita\u0308t Freiburg, D-79106 Freiburg"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ju\u0308rgen","family":"Hausmann","sequence":"additional","affiliation":[{"name":"Abteilung Virologie, Institut fu\u0308r Medizinische Mikrobiologie und Hygiene, Universita\u0308t Freiburg, D-79104 Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Hofer","sequence":"additional","affiliation":[{"name":"Abteilung Neuropathologie, Pathologisches Institut, Universita\u0308t Freiburg, D-79106 Freiburg"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ngan","family":"Pham-Mitchell","sequence":"additional","affiliation":[{"name":"Department of Neuropharmacology, The Scripps Research Institute, La Jolla, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iain L.","family":"Campbell","sequence":"additional","affiliation":[{"name":"Department of Neuropharmacology, The Scripps Research Institute, La Jolla, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Staeheli","sequence":"additional","affiliation":[{"name":"Abteilung Virologie, Institut fu\u0308r Medizinische Mikrobiologie und Hygiene, Universita\u0308t Freiburg, D-79104 Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Axel","family":"Pagenstecher","sequence":"additional","affiliation":[{"name":"Abteilung Neuropathologie, Pathologisches Institut, Universita\u0308t Freiburg, D-79106 Freiburg"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.71.10.7832-7840.1997"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.3109\/13550289909029747"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.2.599"},{"key":"e_1_3_2_5_2","doi-asserted-by":"crossref","first-page":"818","DOI":"10.4049\/jimmunol.153.2.818","volume":"153","year":"1994","unstructured":"Bilzer, T., and L. 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