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

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.