title: Frequent proviral integration of the human betaretrovirus in biliary epithelium of patients with autoimmune and idiopathic liver disease.
abstract: BACKGROUND
  A human betaretrovirus (HBRV) has been linked with primary biliary cirrhosis (PBC) following the detection of viral particles in biliary epithelium by electron microscopy and cloning of the betaretrovirus genome from biliary epithelium and peri-hepatic lymph nodes. Evidence for viral infection was found in the majority of PBC patients' peri-hepatic lymph node samples. However, less than a third of the liver samples had detectable HBRV, whereas others were unable to detect betaretrovirus infection or noted the presence of virus in the liver of patients with other diagnoses.
  
  
  OBJECTIVE
  To address the hypothesis that the betaretrovirus may be below the limits of detection in the liver, biliary epithelial cells (BEC) were investigated for the evidence of infection.
  
  
  METHODS
  Ligation-mediated PCR and next generation sequencing were used to detect proviral integrations in liver, lymph nodes and BEC isolated from liver transplant recipients. Hybridisation-based assays were used to detect betaretroviral RNA in BEC.
  
  
  RESULTS
  Unique HBRV integrations and betaretrovirus RNA were detected in the majority of biliary epithelia derived from patients with PBC, autoimmune hepatitis and cryptogenic liver disease but rarely in other liver transplant recipients with primary sclerosing cholangitis and other hepatic disorders. HBRV integrations were commonly found in PBC patients' lymph nodes but rarely in whole liver samples.
  
  
  CONCLUSIONS
  Human betaretrovirus infection is frequently observed at the site of disease in patients with primary biliary cirrhosis and also in biliary epithelium of patients with autoimmune hepatitis and cryptogenic liver disease.
authors.affiliation: Center of Excellence for Gastrointestinal Inflammation and Immunity Research, University of Alberta, Edmonton, AB, Canada.
authors.forename: W
authors.initials: W
authors.lastname: Wang
authors.forename: S
authors.initials: S
authors.lastname: Indik
authors.forename: S T
authors.initials: ST
authors.lastname: Wasilenko
authors.forename: A
authors.initials: A
authors.lastname: Faschinger
authors.forename: E J
authors.initials: EJ
authors.lastname: Carpenter
authors.forename: Z
authors.initials: Z
authors.lastname: Tian
authors.forename: Y
authors.initials: Y
authors.lastname: Zhang
authors.forename: G K-S
authors.initials: GK
authors.lastname: Wong
authors.forename: A L
authors.initials: AL
authors.lastname: Mason
mesh_terms: D000328:Adult; D030121:Betaretrovirus; D004848:Epithelium / Q000473:pathology; D005260:Female; D019693:Hepatitis, Autoimmune / Q000821:virology*; D022781:Hepatocytes / Q000821:virology*; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008105:Liver Cirrhosis, Biliary / Q000821:virology*; D008107:Liver Diseases / Q000821:virology; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012367:RNA, Viral
chemical_list: D012367:RNA, Viral