Biological impact of hepatitis B virus X-hepatitis C virus core fusion gene on human hepatocytes.
OBJECTIVE
To investigate the biological impact of hepatitis B virus X- hepatitis C virus core (HBV X-HCV C) fusion gene on hepatoma cells.


METHODS
The recombinant adenoviruses Ad-XC, Ad-X and Ad-C expressing HBV X-HCV C fusion gene, HBV X gene and HCV C gene were constructed, respectively. Hepatoma cells were infected with different recombinant adenoviruses. MTT, colony-forming experiment, FCM, TUNEL assay were performed to observe the biological impact of the HBV X-HCV C fusion gene on liver cells.


RESULTS
MTT showed that the Ad-XC group cells grew faster than the other group cells. Colony-forming experiment showed that the colony-forming rate for the Ad-XC group cells was significantly higher than that for the other group cells. FCM analysis showed that Ad-XC/Ad-X/Ad-C infection enhanced the progression of G1-->S phase in the HepG2 cell cycle. The apoptosis index of the Ad-XC, Ad-X, Ad-C group cells was significantly lower than that of the Ad0 and control group cells. Semi-quantitative RT-PCR showed that the expression level of c-myc was the highest in Ad-XC infected cells. Tumor formation was found at the injected site of mice inoculated with Ad-XC-infected LO2 cells, but not in control mice.


CONCLUSIONS
Ad-XC, Ad-X and Ad-C facilitate the proliferation activity of HepG2 cells and inhibit their apoptosis in vitro. The effect of Ad-XC is significantly stronger than that of Ad-X and Ad-C. Up-regulation of c-myc may be one of the mechanisms underlying the synergism of HBV X and HCV C genes on hepatocarcinogenesis in athymic nude mice.
Ma
Zhen
Z
Institute for Viral Hepatitis, Chongqing Medical University, Chongqing, China. mazhen1972@163.com
Shen
Qin-Hai
QH
Chen
Guo-Min
GM
Zhang
Da-Zhi
DZ
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D017209:Apoptosis; D001483:Base Sequence; D006528:Carcinoma, Hepatocellular / Q000473:pathology / Q000821:virology; D002453:Cell Cycle; D045744:Cell Line, Tumor; D004279:DNA, Viral / Q000235:genetics; D050939:Gene Fusion; D005814:Genes, Viral; D016174:Hepacivirus / Q000235:genetics / Q000472:pathogenicity; D006515:Hepatitis B virus / Q000235:genetics / Q000472:pathogenicity; D018936:Hepatitis C Antigens / Q000235:genetics*; D022781:Hepatocytes / Q000473:pathology* / Q000821:virology*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D015534:Trans-Activators / Q000235:genetics*; D014758:Viral Core Proteins / Q000235:genetics*; D054334:Viral Regulatory and Accessory Proteins / Q000235:genetics*
D004279:DNA, Viral; D018936:Hepatitis C Antigens; D015534:Trans-Activators; D014758:Viral Core Proteins; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein