丙型肝炎病毒核心蛋白与信号转导及转录活化蛋白3的相互作用

Interaction between core protein of hepatitis C virus and signal transducer and activator of transcription 3

为了观察丙型肝炎病毒（HCV）核心蛋白（CORE）对信号转导及转录活化蛋白3（STAT3）表达的影响，寻找CORE与STAT3相互作用的功能区域。对Huh-7、转染表达CORE的Huh-7和含有全长HCV基因的复制子（Replicon）Huh-7的STAT3及磷酸化STAT3（p-STAT3）表达水平作比较；并对CORE与STAT3进行免疫共沉淀试验、谷胱甘肽S转移酶（GST）结合试验。结果显示，CORE能直接结合并诱导STAT3和p-STAT3表达，不同病毒株CORE及CORE不同功能区域结合STAT3和p-STAT3能力不同，CORE结合于STAT3主要依耐于CORE的N端的1～126氨基酸。因此，CORE与STAT3的相互作用可能是HCV感染又一新的分子致病机制，在引起HCV持续感染和肝细胞癌的发病机制中起重要作用。

In order to observe the influence of CORE of hepatitis C virus （HCV） on the expression of signal transducer and activator of transcription 3 （STAT3）, and map the interaction domain of CORE and STAT3, the expression levels of STAT3 and phosphorylated STAT3 （p-STAT3） in Huh-7 cells transfected with CORE plasmid and Huh-7 replicon harboring the selected full lenth of HCV genome were compared. In addition, co-immunoprecipitation and glutathione S-transferase （GST） binding assay were performed between CORE and STAT3. It was demonstrated that CORE could directly bind with STAT3 and p-STAT3, and induce their expressions, in which the binding affinities of CORE from different strains of HCV as well as the different domains of CORE with STAT3 and p-STAT3 were quite different and the binding of CORE with STAT3 deponded mainly on the N-terminal 1 - 126 amino acid residues of CORE. These results indicate that the interaction of CORE with STAT3 may provide a new molecular pathogenetic mechanism for HCV infection which might play an important role in the pathogenesis of HCV persistant infection and development of hepatocellular carcinoma.