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Preventive measure of the development of hepatocellular carcinoma by hepatitis C virus infection

丙型肝炎病毒感染引起肝细胞癌的预防措施

基本信息

批准号：
12212001
负责人：
SHIMOTOHNO Kunitada
金额：
$ 44.93万
依托单位：
Kyoto University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research on Priority Areas
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2004
项目状态：
已结题

项目摘要

Hepatitis C virus (HCV) is a causative agent for the development of chronic hepatitis. HCV infection is also shown to be an important agent for the development of hepatocellular carcinoma, but the precise mechanism for the development of these diseases remains to be elucidated. Current researches suggest the significant roles of HCV proteins on the disease progression. Thus, I have conducted experiments to analyze the roles of HCV protein on regulation of cell proliferation and disclosed the following evidence ; (1) HCV core protein has potential, to enhance NF-kB signaling, (2) HCV core protein enhances RARa dependent transcription by way of sequestration of transcriptional suppressor protein Sp110b, (3) HCV NS5A protein has function to regulate PKR by the interaction with PKR through the almost two-thirds of NS5A protein. For the preventive measure of HCV infection as well as for eradication of HCV from infected individuals, analysis of HCV genome replication in HCV genome self-replicating cells was conducted. And the following new finding was made by the analysis ; (1) replication of HCV genome seems to be conducted in a complex protected by ER derived membrane, which mainly localizes on ER, (2) replication of the HCV genome is strictly regulated by innate immunity signaling, in particular, those activated by TLR3, (3) HCV genome replication is positively regulated by cyclophilin B. Some of these information may be applicable for the development of a new agent with anti-HCV function.

丙型肝炎病毒（HCV）是导致慢性肝炎发展的病原体。HCV感染也被证明是肝细胞癌发展的重要因素，但这些疾病发展的确切机制仍有待阐明。目前的研究表明，HCV蛋白在疾病进展中起重要作用。因此，我进行了实验来分析HCV蛋白在细胞增殖调节中的作用，并公开了以下证据：（1）HCV核心蛋白具有增强NF-κ B信号传导的潜力，（2）HCV核心蛋白通过隔离转录抑制蛋白Sp110 b增强RAR α依赖性转录，（3）HCV NS 5A蛋白通过约2/3的NS 5A蛋白与PKR相互作用，对PKR具有调节作用。为了预防HCV感染以及从感染个体中根除HCV，进行了HCV基因组自我复制细胞中HCV基因组复制的分析。HCV基因组的复制受先天免疫信号的调控，尤其是受TLR 3激活的信号的调控; HCV基因组的复制受亲环素B的正调控。其中一些信息可能适用于开发具有抗HCV功能的新药。

项目成果

期刊论文数量（76）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Kato N, et al.: "Establishment of a hepatitis C virus subgenomic replicon derived from human hepatocytes infected in vitro"Biochem Biophys Res Commun.. 306. 756-766 (2003)

Kato N 等：“源自体外感染的人肝细胞的丙型肝炎病毒亚基因组复制子的建立”Biochem Biophys Res Commun.. 306. 756-766 (2003)

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Ueda Y, et al.: "Wnt/b-catenin signaling suppresses apoptosis in low serum medium and induces morphological change in rodent fibroblasts"Int.J.Cancer. 99. 681-688 (2002)

Ueda Y 等人：“Wnt/b-连环蛋白信号传导抑制低血清培养基中的细胞凋亡并诱导啮齿动物成纤维细胞的形态变化”Int.J.Cancer。

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Cytoplasmic localization is important for transcription factor nuclear factor-kappa B activation by hepatitis C virus core protein though its amino terminal region.

细胞质定位对于丙型肝炎病毒核心蛋白通过其氨基末端区域激活转录因子核因子-κB 很重要。

DOI：
发表时间：
2001
期刊：
Virology 286
影响因子：
0
作者：
Kishine H;Sugiyama K;Hijikata M;Kato N;Takahashi H;Noshi T;Nio Y;Hosaka M;Miyanari Y;Shimotohno K.;Watashi K.et al.
通讯作者：
Watashi K.et al.

Watashi K, et al.: "K.The roles of hepatitis C virus proteins in modulation of cellular functions : A novel action mechanism of the HCV core protein on gene regulation by nuclear hormone receptors"Cancer Sci. 94. 937-943 (2003)

Watashi K 等人：“K.丙型肝炎病毒蛋白在细胞功能调节中的作用：HCV 核心蛋白对核激素受体基因调节的新作用机制”Cancer Sci。