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 environmental factors, such as infectious 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. We have found that most patients with PBC have evidence of viral infection and respond to combination anti-retroviral therapy. However, some of the antiviral therapies are not well tolerated and we are trying to find better regimens by inhibiting virus replication in cell cultures. Recently, we have found that several of the mouse models used to study PBC have evidence of mouse mammary tumor virus. We have used one model in particular to try out different antiviral treatments and found that the biliary disease is blocked by different combinations of antiviral therapy. Now we plan to investigate novel therapies in the mouse to see if they work for patients with PBC.