{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T08:10:04Z","timestamp":1770711004581,"version":"3.49.0"},"reference-count":139,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2022,8,31]],"date-time":"2022-08-31T00:00:00Z","timestamp":1661904000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the Canadian Institutes for Health Research","award":["MOP 114998"],"award-info":[{"award-number":["MOP 114998"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Primary biliary cholangitis (PBC) is an autoimmune liver disease characterized by the production of diagnostic antimitochondrial antibodies (AMA) reactive to the pyruvate dehydrogenase complex. A human betaretrovirus (HBRV) resembling mouse mammary tumor virus has been characterized in patients with PBC. However, linking the viral infection with the disease is not a straight-forward process because PBC is a complex multifactorial disease influenced by genetic, hormonal, autoimmune, environmental, and other factors. Currently, PBC is assumed to have an autoimmune etiology, but the evidence is lacking to support this conjecture. In this review, we describe different approaches connecting HBRV with PBC. Initially, we used co-cultivation of HBRV with biliary epithelial cells to trigger the PBC-specific phenotype with cell surface expression of cryptic mitochondrial autoantigens linked with antimitochondrial antibody expression. Subsequently, we have derived layers of proof to support the role of betaretrovirus infection in mouse models of autoimmune biliary disease with spontaneous AMA production and in patients with PBC. Using Hill\u2019s criteria, we provide an overview of how betaretrovirus infection may trigger autoimmunity and propagate biliary disease. Ultimately, the demonstration that disease can be cured with antiviral therapy may sway the argument toward an infectious disease etiology in an analogous fashion that was used to link H. pylori with peptic ulcer disease.<\/jats:p>","DOI":"10.3390\/v14091941","type":"journal-article","created":{"date-parts":[[2022,9,1]],"date-time":"2022-09-01T03:55:38Z","timestamp":1662004538000},"page":"1941","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Linking Human Betaretrovirus with Autoimmunity and Liver Disease in Patients with Primary Biliary Cholangitis"],"prefix":"10.3390","volume":"14","author":[{"given":"Hussain","family":"Syed","sequence":"first","affiliation":[{"name":"Department of Medicine, University of Alberta, Edmonton, AB T6G 2E1, Canada"},{"name":"Center of Excellence for Gastrointestinal Inflammation and Immunity Research, University of Alberta, Edmonton, AB T6G 2E1, Canada"},{"name":"Li Ka Shing Institute of Virology, University of Alberta, Edmonton, AB T6G 2E1, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tara","family":"Penner","sequence":"additional","affiliation":[{"name":"Center of Excellence for Gastrointestinal Inflammation and Immunity Research, University of Alberta, Edmonton, AB T6G 2E1, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0470-9522","authenticated-orcid":false,"given":"Andrew L.","family":"Mason","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Alberta, Edmonton, AB T6G 2E1, Canada"},{"name":"Center of Excellence for Gastrointestinal Inflammation and Immunity Research, University of Alberta, Edmonton, AB T6G 2E1, Canada"},{"name":"Li Ka Shing Institute of Virology, University of Alberta, Edmonton, AB T6G 2E1, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,8,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"European Association for the Study of the Liver, Hirschfield, G.M., Beuers, U., Corpechot, C., Invernizzi, P., Jones, D., Marzioni, M., and Schramm, C. 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