title: 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.
authors.affiliation: Department of Cellular and Molecular Medicine, Cleveland Clinic Lerner Research Institute, Cleveland, OH.|Department of Pathology, Wake Forest School of Medicine, Winston-Salem, NC.
authors.forename: Daniel
authors.initials: D
authors.lastname: Ferguson
authors.affiliation: Department of Pathology, Wake Forest School of Medicine, Winston-Salem, NC.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Pathology, Wake Forest School of Medicine, Winston-Salem, NC.
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Davis
authors.affiliation: Department of Cellular and Molecular Medicine, Cleveland Clinic Lerner Research Institute, Cleveland, OH.
authors.forename: Robert N
authors.initials: RN
authors.lastname: Helsley
authors.affiliation: Clinical Chemistry, Department of Laboratory Medicine, Karolinska Institute, Stockholm, Sweden.
authors.forename: Lise-Lotte
authors.initials: LL
authors.lastname: Vedin
authors.affiliation: Clinical Chemistry, Department of Laboratory Medicine, Karolinska Institute, Stockholm, Sweden.
authors.forename: Richard G
authors.initials: RG
authors.lastname: Lee
authors.affiliation: Clinical Chemistry, Department of Laboratory Medicine, Karolinska Institute, Stockholm, Sweden.
authors.forename: Rosanne M
authors.initials: RM
authors.lastname: Crooke
authors.affiliation: Clinical Chemistry, Department of Laboratory Medicine, Karolinska Institute, Stockholm, Sweden.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Graham
authors.affiliation: Department of Anatomic Pathology, Cleveland Clinic, Cleveland, OH.
authors.forename: Daniela S
authors.initials: DS
authors.lastname: Allende
authors.affiliation: Clinical Chemistry, Department of Laboratory Medicine, Karolinska Institute, Stockholm, Sweden.
authors.forename: Paolo
authors.initials: P
authors.lastname: Parini
authors.affiliation: Department of Cellular and Molecular Medicine, Cleveland Clinic Lerner Research Institute, Cleveland, OH brownm5@ccf.org.
authors.forename: J Mark
authors.initials: JM
authors.lastname: Brown
mesh_terms: D000818:Animals; D005234:Fatty Liver / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D055785:Gene Knockdown Techniques; D005838:Genotype; D016174:Hepacivirus; D006526:Hepatitis C / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D006801:Humans; D066292:Lipid Droplets / Q000378:metabolism / Q000473:pathology / Q000821:virology; D050356:Lipid Metabolism / Q000235:genetics; D008099:Liver / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D051379:Mice; D016376:Oligonucleotides, Antisense / Q000008:administration & dosage / Q000235:genetics; D000070796:Perilipin-3 / Q000037:antagonists & inhibitors / Q000235:genetics*
chemical_list: D016376:Oligonucleotides, Antisense; D000070796:Perilipin-3
keywords: lipid droplets; lipoproteins/metabolism; liver; triglyceride