Hepatitis C virus core can induce lipid droplet formation in a yeast model system

Abstract

Chronic infection with the hepatitis C virus (HCV) frequently induces steatosis, which is characterized by the accumulation of lipid droplets (LDs) in hepatocytes. Steatosis is a significant risk factor for liver cancer. The HCV structural protein core is distributed on the surface of the endoplasmic reticulum (ER) and in LDs, thereby increasing LD levels. In this work, we attempt to elucidate the effect of the core protein on LD generation using yeast cells. We found that the core localized to the cytosolic surface of the ER in yeast and is able to increase LD levels when overexpressed from an inducible GAL1 promoter for 3 hr. The effect of the core was conserved among three different HCV serotypes: 1b, 2a and 3a. While the ER stress inducer tunicamycin both elicited an unfolded stress response (UPR) and increased LD levels, the core did not induce the UPR. The RNA viral genome changes rapidly due to its high mutation rate in order to replicate under a variety of circumstances. Our observations suggest a functional analogy between core function in hepatocytes and in yeast cells and thus might be applicable to the screening of small molecules that impair the core-ER interaction.