TY  - JOUR
A1  - Holdener, Martin
A1  - Hintermann, Edith
A1  - Bayer, Monika
A1  - Rhode, Antje
A1  - Rodrigo, Evelyn
A1  - Hintereder, Gudrun
A1  - Johnson, Eric F.
A1  - Gonzalez, Frank J.
A1  - Pfeilschifter, Josef
A1  - Manns, Michael P.
A1  - Herrath, Matthias G. von
A1  - Christen, Urs
T1  - Breaking tolerance to the natural human liver autoantigen cytochrome P450 2D6 by virus infection
T2  - Journal of experimental medicine
N2  - 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, “fused” 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.
Y1  - 2008
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/6767
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30-68430
SN  - 1540-9538
SN  - 1540-9358
SN  - 0022-1007
N1  - This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jgp.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
VL  - 205
IS  - 6, Art. 1409
SP  - 1409
EP  - 1422
PB  - Rockefeller Univ. Press
CY  - New York, NY
ER  -