Grant: Operating Grant

Patients with primary biliary cirrhosis (PBC) develop progressive bile duct damage and antibodies that recognize mitochondria. However, the cause of the disease is unknown. It is thought that both genetic susceptibility and environment factors, such as infections agents cause PBC. We have recently characterized a novel retrovirus from PBC patients' liver samples that resembles a mouse virus known as mouse mammary tumor virus. While most patients with PBC have evidence of viral infection and respond to combination anti-retroviral therapy, the study of PBC has been hampered by the lack of a good animal model. Recently, a mouse model of autoimmune biliary disease has been reported where the mouse develops progressive biliary damage leading to liver failure. This mouse also has the same immune features that have been found in patients with PBC. We have found that mouse mammary tumor virus is associated with the development of autoimmune biliary disease in these mice. Moreover, the biliary disease is blocked by antiviral therapy. Now we plan to investigate novel therapies in the mouse to see if they work for patients with PBC.