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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >A genome-wide genetic screen for host factors required for hepatitis C virus propagation
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A genome-wide genetic screen for host factors required for hepatitis C virus propagation

机译:丙型肝炎病毒传播所需宿主因子的全基因组遗传筛选

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摘要

Hepatitis C virus (HCV) infection is a major cause of end-stage liver disease and a leading indication for liver transplantation. Current therapy fails in many instances and is associated with significant side effects. HCV encodes only a few proteins and depends heavily on host factors for propagation. Each of these host dependencies is a potential therapeutic target. To find host factors required by HCV, we completed a genome-wide small interfering RNA (siRNA) screen using an infectious HCV cell culture system. We applied a two-part screening protocol to allow identification of host factors involved in the complete viral lifecycle. The candidate genes found included known or previously identified factors, and also implicate many additional host cell proteins in HCV infection. To create a more comprehensive view of HCV and host cell interactions, we performed a bioinformatic meta-analysis that integrates our data with those of previous functional and proteomic studies. The identification of host factors participating in the complete HCV lifecycle will both advance our understanding of HCV pathogenesis and illuminate therapeutic targets.
机译:丙型肝炎病毒(HCV)感染是终末期肝病的主要原因,也是肝移植的主要指征。当前的治疗在许多情况下失败,并伴有明显的副作用。 HCV仅编码几种蛋白质,并且在很大程度上取决于宿主因子的繁殖。这些宿主依赖性中的每一个都是潜在的治疗靶标。为了找到HCV所需的宿主因子,我们使用感染性HCV细胞培养系统完成了全基因组范围的小干扰RNA(siRNA)筛选。我们应用了一个分为两部分的筛查方案,以鉴定涉及完整病毒生命周期的宿主因素。发现的候选基因包括已知或先前鉴定的因子,并且还暗示了HCV感染中许多其他宿主细胞蛋白。为了更全面地了解HCV和宿主细胞之间的相互作用,我们进行了生物信息学荟萃分析,将我们的数据与以前的功能和蛋白质组学研究相结合。鉴定参与完整HCV生命周期的宿主因素既可以增进我们对HCV发病机理的了解,也可以阐明治疗靶标。

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  • 作者单位

    Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892;

    Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard Medical School, Charlestown, MA 02129rnGastrointestinal Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114 Department of Genetics, Harvard Medical School, Division of Genetics, Brigham and Women's Hospital, Howard Hughes Medical Institute, Boston, MA 02115;

    Center for Computational and Integrative Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114;

    Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892;

    Gastrointestinal Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114 Center for Computational and Integrative Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114;

    Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892;

    Department of Genetics, Harvard Medical School, Division of Genetics, Brigham and Women's Hospital, Howard Hughes Medical Institute, Boston, MA 02115;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    HCV; RNA interference; viral host factors; functional genomics; viral lifecycle;

    机译:丙型肝炎病毒;RNA干扰;病毒宿主因素;功能基因组学;病毒生命周期;

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