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

干扰素刺激基因库的构建及肝炎病毒治疗新药的筛选

基本信息

批准号：
18390218
负责人：
CHAYAMA Kazuaki
金额：
$ 9.35万
依托单位：
Hiroshima University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2006
资助国家：
日本
起止时间：
2006 至 2007
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18390218/
关键词：
interferon hepatitis C virus interferon stimulated genes expression profile microarray mRNA human hepatocyte chimeric mouse therapeutic drug 肝炎ウイルスゲノムキメラマウス免疫

项目摘要

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.

我们通过注射从慢性乙型肝炎和丙型肝炎病毒携带者的血清样本中获得的血清样本，使人肝细胞嵌合小鼠感染乙型肝炎和丙型肝炎病毒。在确认小鼠出现病毒血症后，我们每天肌注 7000 U/g α 干扰素。在所有接受治疗的小鼠中观察到丙型肝炎病毒RNA水平迅速下降，相比之下，在感染乙型肝炎病毒的小鼠中仅观察到乙型肝炎病毒DNA微弱减少。我们还给一些人肝细胞嵌合小鼠施用了等量的干扰素。我们处死并收集每只小鼠的肝脏样本，并从每只小鼠中提取 mRNA。我们使用它们的 mRNA 样本进行了微阵列分析。我们从对照、未感染和未干扰素治疗的小鼠中获得了表达谱。我们比较了从乙型肝炎病毒和丙型肝炎病毒感染的小鼠以及用干扰素治疗的感染乙型和丙型肝炎病毒并用干扰素治疗的小鼠获得的小鼠肝脏的表达谱。在感染丙型肝炎病毒的小鼠中观察到干扰素刺激基因的上调。在感染乙型肝炎病毒的小鼠中，这些基因的上调并不那么显着。有趣的是，与未感染的小鼠相比，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弱。目前正在进行进一步的研究，以分析强调干扰素刺激基因产生的抑制的机制。