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

摘要:

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。

Abstract:

Abstract: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 2 diabetes 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 T2DM． 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 T2DM，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.