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


CONCLUSIONS
In conclusion, our results establish GBV-C as a hepatotropic virus infecting human cells of hepatic origin in vivo and in vitro.
Seipp
S
S
Department of Internal Medicine, University of Heidelberg, Germany. stefanie-seipp@www.zoo.uni-heidelberg.de
Scheidel
M
M
Hofmann
W J
WJ
Töx
U
U
Theilmann
L
L
Goeser
T
T
Kallinowski
B
B
D006528:Carcinoma, Hepatocellular / Q000821:virology*; D002460:Cell Line; D003001:Cloning, Molecular; D018067:Flaviviridae / Q000302:isolation & purification / Q000502:physiology*; D006525:Hepatitis, Viral, Human / Q000097:blood / Q000473:pathology / Q000821:virology*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008099:Liver / Q000473:pathology / Q000821:virology*; D008113:Liver Neoplasms / Q000821:virology*; D012367:RNA, Viral / Q000235:genetics / Q000302:isolation & purification; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured; D014779:Virus Replication
D012367:RNA, Viral