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HCV NS5A and NS5B Enhance Expression of Human Ceramide Glucosyltransferase Gene
  • ISSN号:1674-0769
  • 期刊名称:《中国病毒学:英文版》
  • 时间:0
  • 分类:Q78[生物学—分子生物学] TQ658[化学工程—精细化工]
  • 作者机构:[1]State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, China, [2]China Center for Type Culture Collection, Wuhan University, Wuhan 430072, China
  • 相关基金:Foundation item: the National "973" Program of China (No. 2011 CB504800).We thank Prof. Ye Linbo for the HCV polyclonal antibodies. This work was supported by the national "973" program of China (No. 2011CB504800) to CZ.
中文摘要:

涉及类脂化合物新陈代谢的主人基因是在丙肝的早阶段期间影响的差别病毒(HCV ) 感染。当房间与制霉菌素被对待时,这里,我们证明丰满的酸生合成的人工的起来规定在 HCV 全身的 replicon 的复制上有积极效果。相反地,当丰满的酸生合成与 25-hydroxycholesterol 和 PDMP (D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol ) 被禁止时, HCV RNA 复制被减少。与这些结果一致, GlcT-1 (ceramide glucosyltransferase ) 的表达式水平,在 GSL (glycosphingolipid ) 生合成的第一步的主机 glucosyltransferase,被发现仔细与 HCV RNA 的表达式和复制被联系。在另一方面,病毒的 RNA 能也在 vitro 在病毒的 RNA transfection 的早阶段激活 GlcT-1。识别为 GlcT-1 激活负责的病毒的因素,我们构造了表示单个 HCV 蛋白质的十根稳定的 Vero 房间线。基于这些房间线和 GlcT-1 倡导者区域的短暂 transfection 试金的分析,我们结束那 HCV 蛋白质,特别 NS5A 和 NS5B,在 GlcT-1 的表示上有积极效果。NS5A 和 NS5B 刺激抄写因素由增加它的抄写水平激活 GlcT-1 的表示,是可能的。

英文摘要:

Host genes involved in lipid metabolism are differentially affected during the early stages of hepatitis C virus (HCV) infection. Here we demonstrate that artificial up-regulation of fatty acid biosynthesis has a positive effect on the replication of the HCV full-length replicon when cells were treated with nystatin. Conversely, the HCV RNA replication was decreased when fatty acid biosynthesis was inhibited with 25-hydroxycholesterol and PDMP(D-threo-l-phenyl-2-decanoylamino-3- morpholino-l-propanol). In agreement with these results, the expression level of GlcT-l(ceramide glucosyltransferase), a host glucosyltransferase in the first step of GSL (glycosphingolipid) biosynthesis, was found to be closely associated with the expression and replication of HCV RNA. On the other hand, the viral RNA can also activate GlcT-1 in the early stage of viral RNA transfection in vitro. To identify viral factors that are responsible for GlcT-1 activation, we constructed ten stable Vero cell lines that express individual HCV proteins. Based on the analyses of these cell lines and transient transfection assay of the GlcT-1 promoter regions, we conclude that HCV proteins, especially NS5A and NS5B, have positive effects on the expression of GlcT-1. It is possible that NS5A and NS5B stimulate transcription factor(s) to activate the expression of GlcT-1 by increasing its transcription level

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期刊信息
  • 《中国病毒学:英文版》
  • 中国科技核心期刊
  • 主管单位:中国科学院
  • 主办单位:中国科学院武汉病毒研究所 中国微生物学会
  • 主编:陈新文
  • 地址:湖北省武汉市武昌区小洪山中区44号
  • 邮编:430071
  • 邮箱:info@virosin.org
  • 电话:027-87199157
  • 国际标准刊号:ISSN:1674-0769
  • 国内统一刊号:ISSN:42-1760/Q
  • 邮发代号:38-351
  • 获奖情况:
  • 湖北省第1、2、3、4、5、6届优秀期刊,中国科学技术学会 优秀国际科技期刊,2012年中国国际影响力优秀学术期刊
  • 国内外数据库收录:
  • 美国化学文摘(网络版),波兰哥白尼索引,荷兰医学文摘,美国生物医学检索系统,美国剑桥科学文摘,美国生物科学数据库,中国中国科技核心期刊
  • 被引量:208