The lipid droplet-associated protein perilipin 3 facilitates hepatitis C virus-driven hepatic steatosis

Abstract

Hepatitis C virus (HCV) is an enveloped RNA virus responsible for 170 million cases of viral hepatitis worldwide. Over 50% of chronically infected HCV patients develop hepatic steatosis, and steatosis can be induced by expression of HCV core protein (core) alone. Additionally, core must associate with cytoplasmic lipid droplets (LDs) for steatosis development and viral particle assembly. Due to the importance of the LD as a key component of hepatic lipid storage and as a platform for HCV particle assembly, it seems this dynamic subcellular organelle is a gatekeeper in the pathogenesis of viral hepatitis. Here, we hypothesized that core requires the host LD scaffold protein, perilipin (PLIN)3, to induce hepatic steatosis. To test our hypothesis in vivo, we have studied core-induced hepatic steatosis in the absence or presence of antisense oligonucleotide-mediated knockdown of PLIN3. PLIN3 knockdown blunted HCV core-induced steatosis in transgenic mice fed either chow or a moderate fat diet. Collectively, our studies demonstrate that the LD scaffold protein, PLIN3, is essential for HCV core-induced hepatic steatosis and provide new insights into the pathogenesis of HCV.-Ferguson, D., J. Zhang, M. Davis, R. N. Helsley, L-L. Vedin, R. G. Lee, R. M. Crooke, M. J. Graham, P. Parini, and J. M. Brown. The lipid droplet-associated protein perilipin 3 facilitates hepatitis C virus-driven hepatic steatosis. J. Lipid Res. 2017. 58: 420-432.