Does a betaretrovirus infection trigger primary biliary cirrhosis?
Open Access
- 27 June 2003
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 100 (14), 8454-8459
- https://doi.org/10.1073/pnas.1433063100
Abstract
Patients with primary biliary cirrhosis develop progressive ductopenia associated with the production of antimitochondrial antibodies that react with a protein aberrantly expressed on biliary epithelial cells and peri-hepatic lymph nodes. Although no specific microbe has been identified, it is thought that an infectious agent triggers this autoimmune liver disease in genetically predisposed individuals. Previous serologic studies have provided evidence to suggest a viral association with primary biliary cirrhosis. Here we describe the identification of viral particles in biliary epithelium by electron microscopy and the cloning of exogenous retroviral nucleotide sequences from patients with primary biliary cirrhosis. The putative agent is referred to as the human betaretrovirus because it shares close homology with the murine mammary tumor virus and a human retrovirus cloned from breast cancer tissue. In vivo, we have found that the majority of patients with primary biliary cirrhosis have both RT-PCR and immunohistochemistry evidence of human betaretrovirus infection in lymph nodes. Moreover, the viral proteins colocalize to cells demonstrating aberrant autoantigen expression. In vitro, we have found that lymph node homogenates from patients with primary biliary cirrhosis can induce autoantigen expression in normal biliary epithelial cells in coculture. Normal biliary epithelial cells also develop the phenotypic manifestation of primary biliary cirrhosis when cocultivated in serial passage with supernatants containing the human betaretrovirus or the murine mammary tumor virus, providing a model to test Koch's postulates in vitro.Keywords
This publication has 31 references indexed in Scilit:
- Current Concepts in Developmental, Physiologic, and Pathophysiologic Aspects of Cholangiocyte BiologySeminars in Liver Disease, 2002
- PBC: an infectious disease?Gut, 2000
- Expression of pyruvate-dehydrogenase complex PDC-E2 on biliary epithelial cells induced by lymph nodes from primary biliary cirrhosisThe Lancet, 1998
- Ductular Expression of Autoantigens in Primary Biliary CirrhosisSeminars in Liver Disease, 1997
- Immunohistochemical evidence of disease recurrence after liver transplantation for primary biliary cirrhosisHepatology, 1996
- Isolation and culture of biliary epithelial cells.Gut, 1994
- Membrane dihydrolipoamide acetyltransferase (E2) on human biliary epithelial cells in primary biliary cirrhosisThe Lancet, 1992
- Protein-DNA Interactions at Steroid Hormone Regulated GenesEndocrine Research, 1989
- Recurrence of Primary Biliary Cirrhosis after Liver TransplantationNew England Journal of Medicine, 1982
- Relationship between receptor and mammary tumour virus production after stimulation by glucocorticoidNature, 1976