Permissiveness of human biliary epithelial cells to infection by hepatitisC virus

The cellular tropism of hepatitis C virus (HCV) is an important but much de bated issue. Permissivity to HCV of biliary cells has never been demonstrat ed. In this context, we used gallbladder epithelial cells (GBEC) as a model of the more proximal biliary epithelium. These cells were isolated from HC V-positive and -negative individuals and cultured for up to 40 days. Biliar y cells from HCV-negative subjects were infected in vitro with various inoc ula. The retention of GBEC functional characteristics was assessed by the e xpression of cystic fibrosis transmembrane conductance regulator (CFTR), Al l 12 GBEC tested from HCV-negative patients were successfully infected by H CV, This was assessed by: 1) the detection of HCV-RNA positive and negative strands; 2) the detection of the viral capsid by immunofluorescence; and 3 ) the combination of single-strand conformation polymorphism (SSCP) and HVR 1 sequence analysis demonstrating the distinct majoritary HCV genomes in se rum and in GBEC. The level of HCV RNA in cell extracts and supernatants was low, but HCV infection was highly reproducible. Our results expand those s howing the cellular tropism of HCV, and demonstrate the sensitivity of bili ary cells to HCV infection. This might have an important impact in terms of pathogenesis and pathological features of HCV infection. In addition, give n the easy access to these cells and the high reproducibility of in vitro i nfection, they should constitute an important tool for studies aimed at ana lyzing the issue of HCV penetration and neutralizing antibodies.