• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>BMC Chemical Biology >Transcriptional profiling of the effects of 25-hydroxycholesterol on human hepatocyte metabolism and the antiviral state it conveys against the hepatitis C virus
【24h】

Transcriptional profiling of the effects of 25-hydroxycholesterol on human hepatocyte metabolism and the antiviral state it conveys against the hepatitis C virus

机译：转录谱分析25-羟基胆固醇对人肝细胞代谢的影响及其对丙型肝炎病毒传达的抗病毒状态

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Background: Hepatitis C virus (HCV) infection is a global health problem. A number of studies have implicateda direct role of cellular lipid metabolism in the HCV life cycle and inhibitors of the mevalonate pathway have beendemonstrated to result in an antiviral state within the host cell. Transcriptome profiling was conducted on Huh-7 human hepatoma cells bearing subgenomic HCV replicons with and without treatment with 25-hydroxycholesterol (25-HC), an inhibitor of the mevalonate pathway that alters lipid metabolism, to assessmetabolic determinants of pro- and antiviral states within the host cell. These data were compared with geneexpression profiles from HCV-infected chimpanzees.Results: Transcriptome profiling of Huh-7 cells treated with 25-HC gave 47 downregulated genes, 16 of whichare clearly related to the mevalonate pathway. Fewer genes were observed to be upregulated (22) in the presenceof 25-HC and 5 genes were uniquely upregulated in the HCV replicon bearing cells. Comparison of these geneexpression profiles with data collected during the initial rise in viremia in 4 previously characterized HCV-infectedchimpanzees yielded 54 overlapping genes, 4 of which showed interesting differential regulation at the mRNA levelin both systems. These genes are PROX1, INSIG-1, NK4, and UBD. The expression of these genes was perturbedwith siRNAs and with overexpression vectors in HCV replicon cells, and the effect on HCV replication andtranslation was assessed. Both PROX1 and NK4 regulated HCV replication in conjunction with an antiviral stateinduced by 25-hydroxycholesterol.Conclusion: Treatment of Huh-7 cells bearing HCV replicons with 25-HC leads to the downregulation of manykey genes involved in the mevalonate pathway leading to an antiviral state within the host cell. Furthermore,dysregulation of a larger subset of genes not directly related to the mevalonate pathway occurs both in 25-HC-treated HCV replicon harbouring cells as well as during the initial rise in viremia in infected chimpanzees.Functional studies of 3 of these genes demonstrates that they do not directly act as antiviral gene products butthat they indirectly contribute to the antiviral state in the host cell. These genes may also represent novelbiomarkers for HCV infection, since they demonstrate an outcome-specific expression profile.
机译：背景：丙型肝炎病毒（HCV）感染是全球性的健康问题。大量研究表明细胞脂质代谢在HCV生命周期中具有直接作用，并且甲羟戊酸途径的抑制剂已被证明可在宿主细胞内产生抗病毒状态。对携带亚基因组HCV复制子的Huh-7人肝癌细胞进行转录组分析，并用或不用25-羟基胆固醇（25-HC）（一种改变脂质代谢的甲羟戊酸途径的抑制剂）进行治疗，以评估其内抗病毒状态的代谢决定因素宿主细胞。将这些数据与感染HCV的黑猩猩的基因表达谱进行比较。结果：用25-HC处理的Huh-7细胞的转录组谱分析显示47个下调的基因，其中16个与甲羟戊酸途径明显相关。在25-HC的存在下，观察到较少的基因被上调（22），并且在带有HCV复制子的细胞中有5个基因被独特地上调。将这些基因表达谱与在病毒血症最初上升期间在4个先前被HCV感染的黑猩猩进行病毒血症期间收集的数据进行比较，得出54个重叠的基因，其中4个在两个系统中均表现出有趣的mRNA水平差异调节。这些基因是PROX1，INSIG-1，NK4和UBD。在HCV复制子细胞中，这些基因的表达受到siRNA和过表达载体的干扰，并评估了对HCV复制和翻译的影响。结论：用25-HC处理带有HCV复制子的Huh-7细胞会导致许多与甲羟戊酸途径有关的关键基因的下调，从而导致抗病毒状态。在宿主细胞内。此外，在25-HC处理的HCV复制子窝藏细胞中以及在感染黑猩猩的病毒血症初期上升期间，都发生了与甲羟戊酸途径不直接相关的更大基因子的失调。对其中3个基因的功能研究表明：它们不直接充当抗病毒基因产物，而是间接导致宿主细胞中的抗病毒状态。这些基因也可能代表HCV感染的新型生物标志物，因为它们证明了结果特异性表达谱。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号