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[丙型肝炎病毒核心蛋白对信号转导及转录激活因子3活性的调控]

[Regulation of hepatitis C virus core protein on the activity of signal transducers and activators of transcription 3].

作者信息

Feng De-yun, Li Bo, Zheng Hui, Cheng Rui-xue, Cao Ya

机构信息

Department of Pathology, Basic Medical College, China.

出版信息

Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2005 Dec;30(6):631-5.

Abstract

OBJECTIVE

To investigate the regulation of hepatitis C virus (HCV) core protein on the activity of signal transducers and activators of transcription 3 (stat3).

METHODS

A cell line expressing stable HCV core protein-QSG7701-core was constructed by transfecting the pcDNA3. 1-core (expressing HCV core protein) into the human immortalized hepatocyte line QSG7701. The phosphorylation and DNA binding activity of stat3 were detected by immunocytochemistry, Western blot, and electrophoretic mobility shift assay (EMSA).

RESULTS

The expression level of phosphorylated stat3 in QSG7701-core cells was significantly lower than that in QSG7701-pcDNA3. 1 cells and untransfected QSG7701 cells, but there were no significant differences in the expression levels of total stat3 among the 3 groups. The positive signal of phosphorylated stat3 in nucleus of QSG7701-core cells was obviously weaker than that in QSG7701-pcDNA3. 1 cells and untransfected QSG7701 cells. EMSA showed that DNA binding activity of stat3 in QSG7701-core cells significantly decreased.

CONCLUSION

The expressionof HCV core protein in human hepatocyte line may suppress the phosphorylation and DNA binding activity of stat3, which may be one of the causes for resistance against interferon.

摘要

目的

研究丙型肝炎病毒(HCV)核心蛋白对信号转导子和转录激活子3(STAT3)活性的调控作用。

方法

将pcDNA3.1-core(表达HCV核心蛋白)转染至人永生化肝细胞系QSG7701中,构建稳定表达HCV核心蛋白的细胞系-QSG7701-core。采用免疫细胞化学、蛋白质免疫印迹法及电泳迁移率变动分析(EMSA)检测STAT3的磷酸化水平及DNA结合活性。

结果

QSG7701-core细胞中磷酸化STAT3的表达水平显著低于QSG7701-pcDNA3.1细胞及未转染的QSG7701细胞,但三组中总STAT3的表达水平无显著差异。QSG7701-core细胞细胞核中磷酸化STAT3的阳性信号明显弱于QSG7701-pcDNA3.1细胞及未转染的QSG7701细胞。EMSA结果显示,QSG7701-core细胞中STAT3的DNA结合活性显著降低。

结论

人肝细胞系中HCV核心蛋白的表达可能抑制STAT3的磷酸化及DNA结合活性,这可能是干扰素抵抗的原因之一。

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