{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T08:16:41Z","timestamp":1791965801319,"version":"4.3.4"},"reference-count":64,"publisher":"Rockefeller University Press","issue":"6","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2008,6,9]]},"abstract":"<jats:p>Autoimmune liver diseases, such as autoimmune hepatitis (AIH) and primary biliary cirrhosis, often have severe consequences for the patient. Because of a lack of appropriate animal models, not much is known about their potential viral etiology. Infection by liver-tropic viruses is one possibility for the breakdown of self-tolerance. Therefore, we infected mice with adenovirus Ad5 expressing human cytochrome P450 2D6 (Ad-2D6). Ad-2D6\u2013infected mice developed persistent autoimmune liver disease, apparent by cellular infiltration, hepatic fibrosis, \u201cfused\u201d liver lobules, and necrosis. Similar to type 2 AIH patients, Ad-2D6\u2013infected mice generated type 1 liver kidney microsomal\u2013like antibodies recognizing the immunodominant epitope WDPAQPPRD of cytochrome P450 2D6 (CYP2D6). Interestingly, Ad-2D6\u2013infected wild-type FVB\/N mice displayed exacerbated liver damage when compared with transgenic mice expressing the identical human CYP2D6 protein in the liver, indicating the presence of a stronger immunological tolerance in CYP2D6 mice. We demonstrate for the first time that infection with a virus expressing a natural human autoantigen breaks tolerance, resulting in a chronic form of severe, autoimmune liver damage. Our novel model system should be instrumental for studying mechanisms involved in the initiation, propagation, and precipitation of virus-induced autoimmune liver diseases.<\/jats:p>","DOI":"10.1084\/jem.20071859","type":"journal-article","created":{"date-parts":[[2008,5,13]],"date-time":"2008-05-13T00:45:12Z","timestamp":1210639512000},"page":"1409-1422","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":176,"title":["Breaking tolerance to the natural human liver autoantigen cytochrome P450 2D6 by virus infection"],"prefix":"10.1084","volume":"205","author":[{"given":"Martin","family":"Holdener","sequence":"first","affiliation":[{"name":"1Pharmazentrum Frankfurt\/Zentrum fu\u0308r Arzneimittelforschung, Entwicklung und Sicherheit"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edith","family":"Hintermann","sequence":"additional","affiliation":[{"name":"1Pharmazentrum Frankfurt\/Zentrum fu\u0308r Arzneimittelforschung, Entwicklung und Sicherheit"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monika","family":"Bayer","sequence":"additional","affiliation":[{"name":"1Pharmazentrum Frankfurt\/Zentrum fu\u0308r Arzneimittelforschung, Entwicklung und Sicherheit"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antje","family":"Rhode","sequence":"additional","affiliation":[{"name":"3La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evelyn","family":"Rodrigo","sequence":"additional","affiliation":[{"name":"3La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gudrun","family":"Hintereder","sequence":"additional","affiliation":[{"name":"2Zentrallabor, Johann Wolfgang Goethe University, 60590 Frankfurt am Main, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric F.","family":"Johnson","sequence":"additional","affiliation":[{"name":"4The Scripps Research Institute, La Jolla, CA 92037"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank J.","family":"Gonzalez","sequence":"additional","affiliation":[{"name":"5National Cancer Institute, National Institutes of Health, Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josef","family":"Pfeilschifter","sequence":"additional","affiliation":[{"name":"1Pharmazentrum Frankfurt\/Zentrum fu\u0308r Arzneimittelforschung, Entwicklung und Sicherheit"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael P.","family":"Manns","sequence":"additional","affiliation":[{"name":"6Medizinische Hochschule Hannover, 30623 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias von G.","family":"Herrath","sequence":"additional","affiliation":[{"name":"3La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Urs","family":"Christen","sequence":"additional","affiliation":[{"name":"1Pharmazentrum Frankfurt\/Zentrum fu\u0308r Arzneimittelforschung, Entwicklung und Sicherheit"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2008,5,12]]},"reference":[{"key":"2023072915503000700_BIB1","doi-asserted-by":"crossref","first-page":"1348","DOI":"10.1038\/82161","volume":"6","year":"2000","journal-title":"Nat. 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