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AIM:To characterize the host response to hepatitis B virus(HBV) infection in human hepatocytes transplanted intoimmunocompetent rodent rats tolerized by,and transplantedwith primary human hepatocytes.METHODS:One week after the transplantation,rats wereinoculated with HBV,and viral gene expression,replication,and host response was monitored.RESULTS:HBV DNA was detectable in serum for at least60 days.HBsAg levels rose steadily for 3 weeks post-inoculation and then plateaued at a level of about 0.6 pg/ml.HBV RNA was also found in liver at levels that remainedconstant through the time course.Immunofluorescencerevealed clusters of hepatocytes that stained positive forHBcAg.The presence of HI3V covalently closed circular DNA(cccDNA) in liver was demonstrated using nuclease digestionof single-stranded DNA followed by PCR.Serum ALT levelsrose and reached a peak level of 180 IU/L on day 18,butremained elevated for 60 days.Histology revealed aprogressive predominantly mononuclear Iobular hepatitis.CONCLUSION:These data indicate that human hepatoo/testransplanted into rats rendered tolerant to these cells,wheninfected by HBV,results in biochemical as well as histologicalevidence of hepatitis that accompanies viral gene expression,and DNA replication.
A characterizes the host response to hepatitis B virus (HBV) infection in human hepatocytes transplanted into immunocompetent rodent rats tolerized by, and transplanted with primary human hepatocytes. METHODS: One week after the transplantation, rats were inoculated with HBV, and viral gene expression, replication , and host response was monitored .RESULTS: HBV DNA was detectable in serum for at least 60 days. HBsAg levels rose steadily for 3 weeks post-inoculation and then plateaued at a level of about 0.6 pg / ml. HBV RNA was also found in liver at levels that remainconstant through the time course. Immunofluorescencerevealed clusters of hepatocytes that stained positive for HBcAg.The presence of HI3V covalently closed circular DNA (cccDNA) in liver was demonstrated using nulease digestion of single-stranded DNA followed by PCR. Serum ALT levels and achieved a Peak level of 180 IU / L on day 18, butremained elevated for 60 days. Histology revealed a progressive negative predominantly mononuclear Iobular hepatit is.CONCLUSION: These data indicate that human hepatoo / testransplanted into rats rendered tolerant to these cells, when infected by HBV, results in biochemical as well as histologicalevidence of hepatitis that accompanies viral gene expression, and DNA replication.