Production of interferon stimulated gene library and screening of new therapeutic drug for hepatitis viruses

我们通过注射从慢性乙型肝炎和丙型肝炎病毒携带者血清中提取的血清样本，使人肝细胞嵌合小鼠感染乙型和丙型肝炎病毒。在确认小鼠出现病毒血症后，我们每天肌肉注射7000 U/g α干扰素。在所有治疗过的小鼠中，丙型肝炎病毒RNA水平迅速下降，而在感染乙型肝炎病毒的小鼠中，仅观察到乙型肝炎病毒DNA的微弱下降。我们也给一些人肝细胞嵌合小鼠注射相同量的干扰素。我们从每只小鼠中处死并采集肝脏样本，并从每只小鼠中提取mRNA。利用这些mRNA样本，我们进行了微阵列分析。我们获得了对照、非感染和非干扰素治疗小鼠的表达谱。我们比较了乙型肝炎病毒和丙型肝炎病毒感染小鼠的肝脏表达谱，以及干扰素治疗的乙型肝炎病毒和丙型肝炎病毒小鼠和干扰素治疗的小鼠肝脏表达谱。干扰素刺激基因在丙型肝炎病毒感染小鼠中表达上调，而在乙型肝炎病毒感染小鼠中表达不明显。有趣的是，与未感染丙型肝炎病毒的小鼠相比，感染丙型肝炎病毒的小鼠中一些干扰素刺激基因的上调减少了。目前正在进行进一步的研究，以分析这种抑制干扰素刺激基因产生的机制。

We inflicted human hepatocyte chimerie mice with hepatitis B and hepatitis C viruses by injecting serum samples obtained from serum samples of chronic hepatitis B and hepatitis C virus carriers. After confirming the development of viremia in mice, we administered daily 7000 U/g of alpha interferon intramusculary. A rapid decrease in hepatitis C virus RNA levels was observed in all treated mice In contrast, only faint reduction of hepatitis B virus DNA was observed in mice infected with hepatitis B virus. We also administered the same amount of interferon to some human hepatocyte chimeric mice. We sacrificed and collected liver samples from each mice and extracted mRNA from each maim. Using them mRNA samples we performed microarray analysis. We obtained expression profiles from control, non-infected and non-interferon treated mice. We compared expression profiles of mice liver obtained from hepatitis B virus and hepatitis C virus infected mouse as well as interferon treated mice inflicted with hepatitis B and C viruses and treated with interferon. Up regulation of interferon stimulated genes ware observed in hepatitis C virus infected mice The up regulation of them genes was not so eminent in mice infected with hepatitis B virus. Interestingly, up regulation of some interferon stimulated genes were diminished in mice infected with hepatitis C virus compared with non-infected mouse. Further research is now in progress to analyze a mechanism underlining this suppression of interferon stimulated gene production.