丙型肝炎病毒与转录辅激活因子PGC-1α关系的研究进展  

Relationship between hepatitis C virus and the transcription coactivator PGC- 1α- A review

作　　者：姚文霞[1] 蔡华[1] 彭涛[1,2] 

机构地区：[1]广州医科大学基础学院广州霍夫曼免疫研究所,呼吸疾病国家重点实验室,广东广州510182 [2]广东华南联合疫苗开发院有限公司,广东广州510663

出　　处：《微生物学报》2015年第8期983-990,共8页Acta Microbiologica Sinica

基　　金：国家自然科学基金面上项目(31370204);广东省重大科技专项(2011A080502006);广东省自然科学基金博士启动项目(2014A030310357)~~

摘　　要：目前全世界约有1.85亿人被丙型肝炎病毒感染。除了引发肝脏疾病,丙型肝炎病毒感染亦可能会导致胰岛素抵抗和II型糖尿病。作为转录因子的辅激活子,PGC-1α在能量代谢中发挥着至关重要的作用。肝脏中PGC-1α表达异常升高时,亦可以导致II型糖尿病。此外,近些年研究发现,丙型肝炎病毒的包装释放和极低密度脂蛋白紧密相关;另有研究发现,PGC-1α可以通过下游因子促进极低密度脂蛋白的释放。基于上述阐述,我们推测,一方面HCV感染可以上调PGC-1α的表达并进一步导致II型糖尿病,另一方面,PGC-1α可能通过调控极低密度脂蛋白进而影响HCV病毒颗粒的产生。本文结合Shlomai实验室和我们近期的研究成果,解答了上述推测,对丙型肝炎病毒与PGC-1α两者的关系以及HCV感染调控PGC-1α的具体机制进行了阐述,希望为广大科研人员提供一定的帮助。Approximately 185 million people are or have been infected with Hepatitis C virus（ HCV） worldwide. HCV causes not only severe liver problems but also extra hepatic manifestations,such as insulin resistance（ IR） and type 2diabetes mellitus（ T2DM）. Peroxisome proliferator-activated receptor gamma coactivator 1 alpha（ PGC-1α） is a transcription factor coactivator that plays an essential role in cellular energy metabolism,and cumulative studies link the abnormal high expression of PGC-1α to IR and T2 DM. Besides,HCV hijacks host lipid metabolism for its infection,and the very low density lipoprotein（ VLDL） secretory pathway is exploited to facilitate HCV assembly and secretion;coincidently,PGC-1α is reportedly important in VLDL assembly through a downstream factor. Therefore,we hypothesize that,on the one hand,HCV infection results in WT-PGC-1α / L-PGC-1α high expression which will further lead to T2 DM,on the other hand,WT-PGC-1α and L-PGC-1α demonstrate proviral functions in HCV production through the regulation of VLDL. Combining previous studies in the literature with our current findings,we elaborate the relationship between HCV and PGC-1α,and discuss the mechanism how HCV infection upregulates PGC-1α.

关 键 词：丙型肝炎病毒 WT-PGC-1α L-PGC-1α 内质网应激 

分 类 号：R373.21[医药卫生—病原生物学]