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

J Hepatol. 1999 Apr;30(4):570-9. doi: 10.1016/s0168-8278(99)80186-x.

Abstract

Background/aims: Recently, GB virus C (GBV-C) has been identified as another 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 patients for GBV-C RNA plus- and minus-strand RNA.

Methods: These tissues were examined using nested RT-PCR followed by Southern blot hybridization as well as fluorescence in situ hybridization on liver cryosections. To further substantiate susceptibility of liver cells for GBV-C, in vitro infection of human hepatoma cells (HuH7, HepG2) with GBV-C mono-infected serum was performed.

Results: By reverse transcription followed by nested PCR (RT-PCR), 5 of 6 liver 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 patients). One liver sample was negative for GBV-C RNA. In two specimens we could identify GBV-C infection by in situ hybridization. Virus infection appeared to be restricted to hepatocytes and detection of minus-strand RNA showed viral replication in a few highly infected liver cells. In vitro infection 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 virus infecting human cells of hepatic origin in vivo and in vitro.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Hepatocellular / virology*
  • Cell Line
  • Cloning, Molecular
  • Flaviviridae / isolation & purification
  • Flaviviridae / physiology*
  • Hepatitis, Viral, Human / blood
  • Hepatitis, Viral, Human / pathology
  • Hepatitis, Viral, Human / virology*
  • Humans
  • In Situ Hybridization, Fluorescence
  • Liver / pathology
  • Liver / virology*
  • Liver Neoplasms / virology*
  • RNA, Viral / genetics
  • RNA, Viral / isolation & purification
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transcription, Genetic
  • Tumor Cells, Cultured
  • Virus Replication*

Substances

  • RNA, Viral