Linking human beta retrovirus infection with primary biliary cirrhosis.
Several environmental agents have been linked with primary biliary cirrhosis (PBC) that include bacteria, xenobiotics and viruses. A human beta retrovirus (HBRV) related to mouse mammary tumor virus has been cloned and characterized from patients with PBC. This agent can be detected in the majority of patients' perihepatic lymph nodes by immunochemistry and RT-PCR. The HBRV has recently been isolated in culture and integration sites have been identified in the genome of patients to provide convincing evidence of beta retrovirus infection in patients. Three lines of evidence support a role for the virus in PBC. First, the beta retrovirus is linked with aberrant expression of mitochondrial protein(s) on the biliary epithelium cell (BEC) surface, a disease specific phenotype. Second, the related agent, mouse mammary tumor virus has been linked with autoimmune biliary disease in the NOD.c3c4 mouse model for PBC. In this mouse model, the virus is localized to diseased biliary epithelium that also display aberrant expression of the mitochondrial autoantigens. In translational studies, both patients with PBC and NOD.c3c4 mice demonstrate significant improvement in biliary disease with combination antiviral therapy. An overview of the biological relevance of the beta retrovirus infection in PBC will be discussed in this review.
Mason
A L
AL
Division of Gastroenterology, University of Alberta, Edmonton, AB, Canada. andrew.mason@ualberta.ca
Zhang
G
G
D000818:Animals; D044966:Anti-Retroviral Agents / Q000627:therapeutic use; D004279:DNA, Viral / Q000302:isolation & purification; D004195:Disease Models, Animal; D006801:Humans; D008105:Liver Cirrhosis, Biliary / Q000188:drug therapy / Q000821:virology*; D051379:Mice; D015995:Prevalence; D012190:Retroviridae / Q000235:genetics; D012192:Retroviridae Infections / Q000150:complications*
D044966:Anti-Retroviral Agents; D004279:DNA, Viral