Hepatitis C virus NS5A protein increases hepatic lipid accumulation via induction of activation and expression of PPARgamma.

Steatosis is an established risk factor for disease progression in cases of chronic hepatitis C. Recently it was demonstrated that Hepatitis C virus (HCV) core and non-structural (NS) 2 proteins (NS2) induce lipid accumulation in hepatic cells. However, it has yet to be determined whether other HCV proteins are associated with lipid metabolism. The NS5A augmented the transcriptional activity and gene expression of PPARgamma. Furthermore, NS5A increased the ability to recruit the transcriptional coactivator PGC-1s to the PPRE with PPARgamma, as well as the interaction with PPARgamma2 and PGC-1alpha. Our results indicate that NS5A may exploit multiple strategies that enhance PPARgamma-induced lipid accumulation.