Identification of host factors required for internal ribosomal entry site directed translation of hepatitis C virus

丙型肝炎病毒内部核糖体进入位点定向翻译所需宿主因素的鉴定

基本信息

  • 批准号:
    14570410
  • 负责人:
  • 金额:
    $ 2.56万
  • 依托单位:
  • 依托单位国家:
    日本
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
  • 财政年份:
    2002
  • 资助国家:
    日本
  • 起止时间:
    2002 至 2003
  • 项目状态:
    已结题

项目摘要

Background and aim : Translation of hepatitis C virus(HCV) is an essential step of the viral replication and is mediated by an internal ribosome entry site(IRES). We previously reported that HCV-IRES is most active during the synthetic(S) or mitotic(M) phases and lowest during the quiescent(G0) phases. Here we investigated responsible host factors that regulate HCV-IRES. Methods : We synchronized the cell cycle progression of RCF-26,that constitutively express dicistronic RNA transcripts containing two reporter genes separated by a functional HCV-IRES. Then we evaluated dynamism of genes expression of host factors and kinetics of HCV-IRES activity in cells at various points during the cell cycle using a CDNA microarray. We also validated a significance of identified host factors on HCV replication in vivo. Results : HCV-IRES activity correlated with a gene cluster induced in S and G2/M phases. Interestingly, most of initiation factors that bind or interact with HCV-IRES(PCBP2,PTB,eIF3,eIF2gamma,eIF2 beta, La protein and RNLPL) were induced during the S and G2/M phases. Especially, expressions of La protein, PTB and eBR3(p116,170) were predominantly repressed in quiescent(G0) and induced in S and G2/M phases. The suppression or overexpression of La protein, PTB and eIF3(p170) in RCF-26 significantly changed HCV-IRES activity. In the livers of patients with chronic hepatitis C, the expression of La protein was significantly increased and correlated with the amount of HCV-RNA. Conclusions : The translation of HCV is regulated by cellular proteins that vary in abundance during the cell cycle. Of these, La protein is a potent regulator and would enhance HCV replication in regenerating hepatocytes in patients with chronic hepatitis C.
背景和目标:丙型肝炎病毒(HCV)的翻译是病毒复制的重要步骤,由内部核糖体进入位点(IRES)介导。我们以前报道过HCV-IRES在合成期(S)或有丝分裂期(M)最活跃,在静止期(G 0)最低。在这里,我们调查了负责的主机因素,调节HCV-IRES。研究方法:我们同步的细胞周期进程的RCF-26,组成型表达双顺反子RNA转录含有两个报告基因分开的功能HCV-IRES。然后,我们使用cDNA微阵列评估宿主因子的基因表达动态和细胞周期中不同时间点的细胞中HCV-IRES活性的动态。我们还验证了确定的宿主因子对HCV体内复制的意义。结果:HCV-IRES活性与S期和G2/M期诱导的基因簇相关。有趣的是,大多数与HCV-IRES结合或相互作用的起始因子(PCBP 2、PTB、eIF 3、eIF 2 γ、eIF 2 β、La蛋白和RNLPL)在S期和G2/M期被诱导。尤其是La蛋白、PTB和eBR 3(p116,170)的表达在静止期(G 0)被抑制,而在S期和G2/M期被诱导。RCF-26中La蛋白、PTB和eIF 3(p170)的抑制或过表达显著改变HCV-IRES活性。在慢性丙型肝炎患者肝脏中,La蛋白表达明显增加,并与HCV-RNA含量相关。结论:HCV的翻译受细胞周期中丰度变化的细胞蛋白质的调节。其中,La蛋白是一种有效的调节剂,可增强慢性丙型肝炎患者再生肝细胞中HCV的复制。

项目成果

期刊论文数量(34)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Takeo Shimazaki et al.: "Inhibition of Internal Ribosomal Entry Site-Directed Translation of HCV by Recombinant IFN-a Correlates With a Reduced La Protein"Hepatology. 35. 199-208 (2002)
Takeo Shimazaki 等人:“重组 IFN-α 对 HCV 内部核糖体进入位点定向翻译的抑制与减少的 La 蛋白相关”肝病学。
  • DOI:
  • 发表时间:
  • 期刊:
  • 影响因子:
    0
  • 作者:
  • 通讯作者:
Kawaguchi K, Kaneko S, Honda M.Kawai HF, Shirota Y, Kobayashi K.: "Detection of hepatitis B virus DNA in sera from patients with chronic hepatitis B virus infection by DNA microarray method."J Clin Microbiol. 41. 1701-1704 (2003)
Kawaguchi K、Kaneko S、Honda M.Kawai HF、Shirota Y、Kobayashi K.:“通过 DNA 微阵列方法检测慢性乙型肝炎病毒感染患者血清中的乙型肝炎病毒 DNA。”J Clin Microbiol。
  • DOI:
  • 发表时间:
  • 期刊:
  • 影响因子:
    0
  • 作者:
  • 通讯作者:
Lerat H, Honda M,.Beard MR, Loesch K, Sun J, Yang Y, Okuda M, Gosert R, Xiao SY, Weinman SA, Lemon SM.: "Steatosis and liver cancer in transgenic mice expressing the structural and nonstructural proteins of hepatitis C virus."Gastroenterolpgy. 122(2). 352
Lerat H、Honda M、Beard MR、Loesch K、Sun J、Yang Y、Okuda M、Gosert R、Xiao SY、Weinman SA、Lemon SM.:“表达结构和非结构蛋白的转基因小鼠中的脂肪变性和肝癌
  • DOI:
  • 发表时间:
  • 期刊:
  • 影响因子:
    0
  • 作者:
  • 通讯作者:
Tsuchiyama T, Kaneko S, Nakamoto Y, Sakai Y, Honda M, Mukaida N, Kobayashi K.: "Enhanced antitumor effects of a bicistronic adenovirus vector expressing both herpes simplex virus thymidine kinase and monocyte chemoattractant protein-1 against hepatocellul
Tsuchiyama T、Kaneko S、Nakamoto Y、Sakai Y、Honda M、Mukaida N、Kobayashi K.:“表达单纯疱疹病毒胸苷激酶和单核细胞趋化蛋白-1 的双顺反子腺病毒载体对肝细胞的增强抗肿瘤作用
  • DOI:
  • 发表时间:
  • 期刊:
  • 影响因子:
    0
  • 作者:
  • 通讯作者:
Takamura T, Sakurai M, Ota T, Ando H, Honda M, Kaneko S: "Genes for systemic vascular complications are differentially expressed in the livers of Type 2 diabetic patients"Diabetologia. (印刷中). (2004)
Takamura T、Sakurai M、Ota T、Ando H、Honda M、Kaneko S:“全身血管并发症的基因在 2 型糖尿病患者的肝脏中表达有差异”Diabetologia(出版中)。
  • DOI:
  • 发表时间:
  • 期刊:
  • 影响因子:
    0
  • 作者:
  • 通讯作者:
{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

HONDA Masao其他文献

HONDA Masao的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('HONDA Masao', 18)}}的其他基金

Phosphoproteome analysis of the liver tissues with NAFLD/NASH and identification of therapeutic targets.
NAFLD/NASH 肝组织的磷酸化蛋白质组分析和治疗靶点的鉴定。
  • 批准号:
    18H02793
  • 财政年份:
    2018
  • 资助金额:
    $ 2.56万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Elucidation of the mechanisms of HBV infection using single cell transcriptome analysis
利用单细胞转录组分析阐明 HBV 感染机制
  • 批准号:
    16K15426
  • 财政年份:
    2016
  • 资助金额:
    $ 2.56万
  • 项目类别:
    Grant-in-Aid for Challenging Exploratory Research
Identification of biomarkers to predict HCC development after successful treatment of viral hepatitis
成功治疗病毒性肝炎后鉴定预测 HCC 发展的生物标志物
  • 批准号:
    15H04809
  • 财政年份:
    2015
  • 资助金额:
    $ 2.56万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Establishment new HCC derived cell lines that support efficient hepatitis virus replication.
建立新的 HCC 衍生细胞系,支持肝炎病毒的有效复制。
  • 批准号:
    26670378
  • 财政年份:
    2014
  • 资助金额:
    $ 2.56万
  • 项目类别:
    Grant-in-Aid for Challenging Exploratory Research
Establishment of molecular basis for improving the treatment efficacy of chronic hepatitis C and preventing the occurrence of hepatocellular carcinoma.
为提高慢性丙型肝炎治疗效果、预防肝细胞癌的发生奠定分子基础。
  • 批准号:
    24390187
  • 财政年份:
    2012
  • 资助金额:
    $ 2.56万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Identification of host genes responsible for the treatment response of interferon therapy for the patients with chronic hepatitis C
慢性丙型肝炎患者干扰素治疗反应宿主基因的鉴定
  • 批准号:
    21390227
  • 财政年份:
    2009
  • 资助金额:
    $ 2.56万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Gene expression profiling of peripheral mononuclear cells in blood and liver disease
血液和肝脏疾病中外周单核细胞的基因表达谱
  • 批准号:
    19591161
  • 财政年份:
    2007
  • 资助金额:
    $ 2.56万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Identification of host factors required for HCV-IRES activity and their physiological roles in liver disease
HCV-IRES 活性所需宿主因子的鉴定及其在肝病中的生理作用
  • 批准号:
    17591036
  • 财政年份:
    2005
  • 资助金额:
    $ 2.56万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)

相似海外基金

Translation initiation via factorless internal ribosome entry site mechanisms
通过无因素内部核糖体进入位点机制启动翻译
  • 批准号:
    445272
  • 财政年份:
    2021
  • 资助金额:
    $ 2.56万
  • 项目类别:
    Operating Grants
Studying and targeting a proto-oncogenic Internal Ribosome Entry Site (IRES) in p53 mRNA that is activated by the most frequent mutations in cancer
研究并靶向 p53 mRNA 中的原癌内部核糖体进入位点 (IRES),该位点由癌症中最常见的突变激活
  • 批准号:
    18K07229
  • 财政年份:
    2018
  • 资助金额:
    $ 2.56万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Translation reading frame selection directed by a viral internal ribosome entry site
由病毒内部核糖体进入位点指导的翻译阅读框选择
  • 批准号:
    344516
  • 财政年份:
    2016
  • 资助金额:
    $ 2.56万
  • 项目类别:
    Operating Grants
Using chemical probes to map the interaction between the eukaryotic ribosome and intergenic internal ribosome entry site of the Israeli acute paralysis virus.
使用化学探针绘制真核核糖体与以色列急性麻痹病毒基因间内部核糖体进入位点之间的相互作用。
  • 批准号:
    426307-2012
  • 财政年份:
    2012
  • 资助金额:
    $ 2.56万
  • 项目类别:
    Alexander Graham Bell Canada Graduate Scholarships - Master's
Establishment of predictors in treatment response of chronic hepatitisC by mutational analysis of internal ribosome entry site within hepatitis C virus
通过丙型肝炎病毒内部核糖体进入位点的突变分析建立慢性丙型肝炎治疗反应的预测因子
  • 批准号:
    22590751
  • 财政年份:
    2010
  • 资助金额:
    $ 2.56万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Dissecting Signaling Pathways Regulating Internal Ribosome Entry Site-mediated Translation
剖析调节内部核糖体进入位点介导翻译的信号通路
  • 批准号:
    184668
  • 财政年份:
    2008
  • 资助金额:
    $ 2.56万
  • 项目类别:
    Studentship Programs
Functional Analysis of TEV Internal Ribosome Entry Site
TEV 内部核糖体进入位点的功能分析
  • 批准号:
    0814051
  • 财政年份:
    2008
  • 资助金额:
    $ 2.56万
  • 项目类别:
    Continuing Grant
Identification of predictors in treatment response by mutational analysis of internal ribosome entry site within hepatitis C virus
通过丙型肝炎病毒内部核糖体进入位点的突变分析鉴定治疗反应的预测因子
  • 批准号:
    19790502
  • 财政年份:
    2007
  • 资助金额:
    $ 2.56万
  • 项目类别:
    Grant-in-Aid for Young Scientists (B)
HCV INTERNAL RIBOSOME ENTRY SITE AS TARGET FOR THERAPY
HCV 内部核糖体进入位点作为治疗靶点
  • 批准号:
    2906461
  • 财政年份:
    1999
  • 资助金额:
    $ 2.56万
  • 项目类别:
HCV INTERNAL RIBOSOME ENTRY SITE AS TARGET FOR THERAPY
HCV 内部核糖体进入位点作为治疗靶点
  • 批准号:
    6381649
  • 财政年份:
    1999
  • 资助金额:
    $ 2.56万
  • 项目类别:
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了