Isolation of a Human Betaretrovirus from Patients with Primary Biliary Cholangitis.

A human betaretrovirus (HBRV) has been linked with the autoimmune liver disease, primary biliary cholangitis (PBC), and various cancers, including breast cancer and lymphoma. HBRV is closely related to the mouse mammary tumor virus, and represents the only exogenous betaretrovirus characterized in humans to date. Evidence of infection in patients with PBC has been demonstrated through the identification of proviral integration sites in lymphoid tissue, the major reservoir of infection, as well as biliary epithelium, which is the site of the disease process.

Cyclosporine A inhibits in vitro replication of betaretrovirus associated with primary biliary cirrhosis.

Background/aim: Up to one-third of patients with primary biliary cirrhosis (PBC) experience recurrent disease following liver transplantation, which is associated with earlier and more severe recurrence in patients treated with tacrolimus as compared with cyclosporine A (CsA). As the latter has known antiviral activity, we hypothesized that CsA has the ability to inhibit the betaretrovirus characterized from patients with PBC.

Methods: We investigated whether CsA, the cyclosporine analogue NIM811, tacrolimus and other compounds can modulate the mouse mammary tumour virus production from Mm5MT cells.