Hepatotropism of GB virus C (GBV-C): GBV-C replication in human hepatocytes and cells of human hepatoma cell lines

Background/Aims: Recently, GB virus C (GBV-C) has been identified as anothe r virus potentially causing viral hepatitis However, its hepatotropism and pattern of infection in humans is still unknown. To elucidate the presence and replication of GBV-C in the human liver, we investigated tissue samples of six explanted livers from five GBV-C mono- or GBV-C/ HCV co-infected pa tients for GBV-C RNA plus- and minus-strand RNA. Methods: These tissues were examined using nested RT-PCR followed by Southe rn blot hybridization as well as fluorescence in situ hybridization on live r cryosections. To further substantiate susceptibility of liver cells for G BV-C, in vitro infection of human hepatoma cells (HuH7, HepG2) with GBV-C m onoinfected serum was performed. Results: By reverse transcription followed by nested PCR (RT-PCR), 5 of 6 l iver specimens (4/5 patients) were positive for GBV-C plus-strand RNA, and viral minus-strand RNA could be detected in 4 of 6 liver specimens (4/5 pat ients). One liver sample was negative for GBV-C RNA. In two specimens we co uld identify GBV-C infection by in situ hybridization. Virus infection appe ared to be restricted to hepatocytes and detection of minus-strand RNA show ed viral replication in a few highly infected liver cells. In vitro infecti on of HepG2 or HuH7 cells confirmed these findings by a release of virions into supernatant. Conclusion: In conclusion, our results establish GBV-C as a hepatotropic vi rus infecting human cells of hepatic origin in vivo and in vitro.