{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,4,7]],"date-time":"2025-04-07T18:46:36Z","timestamp":1744051596030,"version":"3.30.0"},"reference-count":21,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":2556,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2008,9]]},"abstract":"<jats:sec>\n            <jats:title\/>\n            <jats:p>\n                                 <jats:italic toggle=\"yes\">Holdener M, Hintermann E, Bayer M, Rhode A, Rodrigo E, Hintereder G, et al.<\/jats:italic> Breaking tolerance to the natural human liver autoantigen cytochrome P450 2D6 by virus infection. J Exp Med 2008; 205:1409-1422. (Reprinted with permission.)<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Abstract<\/jats:title>\n            <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-infected 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-infected mice generated type 1 liver kidney microsomal-like antibodies recognizing the immunodominant epitope WDPAQPPRD of cytochrome P450 2D6 (CYP2D6). Interestingly, Ad-2D6-infected 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>\n          <\/jats:sec>","DOI":"10.1002\/hep.22529","type":"journal-article","created":{"date-parts":[[2008,8,28]],"date-time":"2008-08-28T13:14:44Z","timestamp":1219929284000},"page":"1013-1015","update-policy":"http:\/\/dx.doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":8,"title":["Of mice and molecular mimicry: Modeling autoimmune hepatitis"],"prefix":"10.1097","volume":"48","author":[{"given":"David G.","family":"Bowen","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"R1-34-20241202","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1007\/PL00000716","article-title":"Molecular mimicry: a critical look at exemplary instances in human diseases.","volume":"57","author":"Rose","year":"2000","journal-title":"Cell Mol Life Sci"},{"key":"R2-34-20241202","doi-asserted-by":"crossref","first-page":"1370","DOI":"10.1172\/JCI115443","article-title":"LKM1 autoantibodies recognize a short linear sequence in P450IID6, a cytochrome P450 monooxygenase.","volume":"88","author":"Manns","year":"1991","journal-title":"J Clin Invest"},{"key":"R3-34-20241202","doi-asserted-by":"crossref","first-page":"1481","DOI":"10.4049\/jimmunol.170.3.1481","article-title":"Cytochrome P4502D6(193212): a new immunodominant epitope and target of virusself crossreactivity in liver kidney microsomal autoantibody type 1positive liver disease.","volume":"170","author":"Kerkar","year":"2003","journal-title":"J Immunol"},{"key":"R4-34-20241202","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1053\/jhep.2002.30699","article-title":"Fine specificity of autoantibodies to soluble liver antigen and liverpancreas.","volume":"35","author":"Herkel","year":"2002","journal-title":"HEPATOLOGY"},{"key":"R5-34-20241202","doi-asserted-by":"crossref","first-page":"1485","DOI":"10.1053\/gast.2001.22441","article-title":"The lymphoid liver: considerations on pathways to autoimmune injury.","volume":"120","author":"Kita","year":"2001","journal-title":"Gastroenterology"},{"key":"R6-34-20241202","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1038\/nri981","article-title":"Hepatic T cells and liver tolerance.","volume":"3","author":"Crispe","year":"2003","journal-title":"Nat Rev Immunol"},{"key":"R7-34-20241202","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1016\/j.it.2005.08.005","article-title":"Intrahepatic immunity: a tale of two sites?","volume":"26","author":"Bowen","year":"2005","journal-title":"Trends Immunol"},{"key":"R8-34-20241202","doi-asserted-by":"crossref","first-page":"1541","DOI":"10.1084\/jem.178.5.1541","article-title":"Mechanisms of class I restricted immunopathology. A transgenic mouse model of fulminant hepatitis.","volume":"178","author":"Ando","year":"1993","journal-title":"J Exp Med"},{"key":"R9-34-20241202","doi-asserted-by":"crossref","first-page":"1932","DOI":"10.1002\/eji.1830250721","article-title":"Peripheral deletion of autoreactive CD8 T cells in transgenic mice expressing H2Kb in the liver.","volume":"25","author":"Bertolino","year":"1995","journal-title":"Eur J Immunol"},{"key":"R10-34-20241202","doi-asserted-by":"crossref","first-page":"2395","DOI":"10.1002\/(SICI)1521-4141(199808)28:08<2395::AID-IMMU2395>3.0.CO;2-D","article-title":"Failure to induce organspecific autoimmunity by breaking of tolerance: importance of the microenvironment.","volume":"28","author":"Limmer","year":"1998","journal-title":"Eur J Immunol"},{"key":"R11-34-20241202","doi-asserted-by":"crossref","first-page":"2415","DOI":"10.4049\/jimmunol.165.5.2415","article-title":"Break of T cell ignorance to a viral antigen in the liver induces hepatitis.","volume":"165","author":"Voehringer","year":"2000","journal-title":"J Immunol"},{"key":"R12-34-20241202","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1002\/hep.1840110106","article-title":"Experimental autoimmune hepatitis: disease induction, time course and Tcell reactivity.","volume":"11","author":"Lohse","year":"1990","journal-title":"HEPATOLOGY"},{"key":"R13-34-20241202","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1111\/j.1365-2249.1993.tb05995.x","article-title":"Remission of experimental autoimmune hepatitis is associated with antigenspecific and nonspecific immunosuppression.","volume":"94","author":"Lohse","year":"1993","journal-title":"Clin Exp Immunol"},{"key":"R14-34-20241202","doi-asserted-by":"crossref","first-page":"4889","DOI":"10.4049\/jimmunol.169.9.4889","article-title":"DNA vaccination breaks tolerance for a neoself antigen in liver: a transgenic murine model of autoimmune hepatitis.","volume":"169","author":"DjilaliSaiah","year":"2002","journal-title":"J Immunol"},{"key":"R15-34-20241202","doi-asserted-by":"crossref","first-page":"1066","DOI":"10.1002\/hep.20109","article-title":"A murine model of type 2 autoimmune hepatitis: xenoimmunization with human antigens.","volume":"39","author":"Lapierre","year":"2004","journal-title":"HEPATOLOGY"},{"key":"R16-34-20241202","doi-asserted-by":"crossref","first-page":"1409","DOI":"10.1084\/jem.20071859","article-title":"Breaking tolerance to the natural human liver autoantigen cytochrome P450 2D6 by virus infection.","volume":"205","author":"Holdener","year":"2008","journal-title":"J Exp Med"},{"key":"R17-34-20241202","doi-asserted-by":"crossref","first-page":"S132","DOI":"10.1002\/hep.21059","article-title":"Autoimmune hepatitis, from mechanisms to therapy.","volume":"43","author":"Manns","year":"2006","journal-title":"HEPATOLOGY"},{"key":"R18-34-20241202","doi-asserted-by":"crossref","first-page":"868","DOI":"10.1053\/j.gastro.2005.12.020","article-title":"Polyclonal Tcell responses to cytochrome P450IID6 are associated with disease activity in autoimmune hepatitis type 2.","volume":"130","author":"Ma","year":"2006","journal-title":"Gastroenterology"},{"key":"R19-34-20241202","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1002\/hep.21658","article-title":"Cytochrome P450IID6specific CD8 T cell immune responses mirror disease activity in autoimmune hepatitis type 2.","volume":"46","author":"Longhi","year":"2007","journal-title":"HEPATOLOGY"},{"key":"R20-34-20241202","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/j.jaut.2005.11.001","article-title":"Type 2 autoimmune hepatitis murine model: the influence of genetic background in disease development.","volume":"26","author":"Lapierre","year":"2006","journal-title":"J Autoimmun"},{"key":"R21-34-20241202","doi-asserted-by":"crossref","first-page":"2873","DOI":"10.4049\/jimmunol.171.6.2873","article-title":"Genetic control of NKT cell numbers maps to major diabetes and lupus loci.","volume":"171","author":"Esteban","year":"2003","journal-title":"J Immunol"}],"container-title":["Hepatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fhep.22529","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.lww.com\/01515467-200809000-00034","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,12,2]],"date-time":"2024-12-02T17:06:07Z","timestamp":1733159167000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.lww.com\/01515467-200809000-00034"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,9]]},"references-count":21,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2008]]}},"URL":"https:\/\/doi.org\/10.1002\/hep.22529","relation":{},"ISSN":["0270-9139"],"issn-type":[{"type":"print","value":"0270-9139"}],"subject":[],"published":{"date-parts":[[2008,9]]}}}