Mouse mammary tumor virus in anti-mitochondrial antibody producing mouse models
| Autor: | Mark Kneteman, Andrew Mason, Don Graham, Min Chen, Suzanna Gilady, Guangzhi Zhang, Richard A. Flavell, Michael Trauner, Shawn T. Wasilenko, Stephen H. Wrzesinski, Mark G. Swain, Chelsea McDougall, Lok Man J. Law, Benchamas Subsin |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
viruses
Nod Dihydrolipoyllysine-Residue Acetyltransferase Virus Replication Mitochondrial Proteins Mice Mammary tumor virus Mice Inbred NOD Seroepidemiologic Studies Immunochemistry Animals NOD mice Autoantibodies Mice Knockout Mice Inbred BALB C Mice Inbred C3H Hepatology biology Liver Cirrhosis Biliary Mouse mammary tumor virus Receptors Interleukin biology.organism_classification Virology Mitochondria Mice Inbred C57BL Disease Models Animal Tumor Virus Infections Liver Mammary Tumor Virus Mouse Knockout mouse biology.protein Female Antibody Betaretrovirus Spleen Retroviridae Infections |
| Zdroj: | Journal of hepatology. 55(4) |
| ISSN: | 1600-0641 |
| Popis: | Background & Aims A human betaretrovirus resembling the mouse mammary tumor virus (MMTV) has been characterized in primary biliary cirrhosis (PBC) and associated with aberrant pyruvate dehydrogenase complex (PDC)–E2-like expression. As MMTV is prevalent in mice as either an exogenous or endogenous infection, we tested the hypothesis that MMTV is linked with anti-mitochondrial antibody (AMA) production in models with severe immune dysfunction. Methods Evidence for MMTV was assessed in the liver and spleen of mice by PCR and immunochemistry and PDC-E2-like protein by immunochemistry. ELISA and Western blot were used to investigate AMA and anti-MMTV antibody production. Results Increased MMTV gag or env expression was detected in the livers of AMA producing mice including NOD.c3c4, CD4 directed dominant negative TGF-β receptor II and IL-2 receptor α knockout mice as well as the NOD parental strain when compared to healthy strains and biliary disease control mice. The NOD.c3c4 mice expressed MMTV surface and capsid proteins and aberrant PDC-E2-like protein in the bile ducts, whereas IL-2 receptor α knockout mice, NOD.c3c4 and the NOD mice expressed MMTV proteins and aberrant PDC-E2-like protein in the spleen. A significant correlation between anti-MMTV antibody production and AMA production was observed in the sera of NOD and NOD.c3c4 mice ( p 0.0001). Conclusions The association of betaretroviral protein production and aberrant PDC-E2-like protein expression in the NOD.c3c4, NOD, and the IL-2 receptor α knockout mice is comparable to observations in patients with PBC. The correlation of AMA and anti-MMTV suggests the hypothesis that MMTV infection may trigger the production of AMA. |
| Databáze: | OpenAIRE |
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