The Phospholipid:Diacylglycerol Acyltransferase Lro1 Is Responsible for Hepatitis C Virus Core-Induced Lipid Droplet Formation in a Yeast Model System

• Published in: PloS one Vol. 11; no. 7; p. e0159324
• Main Authors: Iwasa, Shingo, Sato, Naoko, Wang, Chao-Wen, Cheng, Yun-Hsin, Irokawa, Hayato, Hwang, Gi-Wook, Naganuma, Akira, Kuge, Shusuke
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 26.07.2016; Public Library of Science (PLoS)
• Subjects: Acyltransferase; Amino acids; Analysis; Baking yeast; Biodegradation; Biological evolution; Biological Transport; Biology; Biology and Life Sciences; Chronic infection; Core protein; Diacylglycerol; Diacylglycerol O-Acyltransferase - genetics; Diacylglycerol O-Acyltransferase - metabolism; Diglycerides; Droplets; Drug resistance; Endoplasmic reticulum; Endoplasmic Reticulum-Associated Degradation; Enzymes; Fatty liver; Gene Expression; Genetic aspects; Genomes; Health aspects; Hepacivirus - physiology; Hepatitis; Hepatitis C; Hepatitis C virus; Hepatocytes; Laboratories; Lipid Droplets - metabolism; Lipid Metabolism; Lipids; Liver; Liver cancer; Localization; Molecular modelling; Mutation; Mutation rates; Pathogenesis; Pharmaceutical sciences; Phospholipids; Phospholipids - metabolism; Physical Sciences; Prevention; Proteins; Proteolysis; Research and Analysis Methods; Ribonucleic acid; Risk factors; RNA; RNA viruses; Saccharomyces cerevisiae; Steatosis; Toxicology; Viral Core Proteins - genetics; Viral Core Proteins - metabolism; Viruses; Yeast; Yeasts (Fungi); Yeasts - metabolism; Yeasts - virology
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0159324

Chronic infection with the hepatitis C virus frequently induces steatosis, which is a significant risk factor for liver pathogenesis. Steatosis is characterized by the accumulation of lipid droplets in hepatocytes. The structural protein core of the virus induces lipid droplet formation and localizes on the surface of the lipid droplets. However, the precise molecular mechanisms for the core-induced formation of lipid droplets remain elusive. Recently, we showed that the expression of the core protein in yeast as a model system could induce lipid droplet formation. In this study, we probed the cellular factors responsible for the formation of core-induced lipid-droplets in yeast cells. We demonstrated that one of the enzymes responsible for triglyceride synthesis, a phospholipid:diacylglycerol acyltransferase (Lro1), is required for the core-induced lipid droplet formation. While core proteins inhibit Lro1 degradation and alter Lro1 localization, the characteristic localization of Lro1 adjacent to the lipid droplets appeared to be responsible for the core-induced lipid droplet formation. RNA virus genomes have evolved using high mutation rates to maintain their ability to replicate. Our observations suggest a functional relationship between the core protein with hepatocytes and yeast cells. The possible interactions between core proteins and the endoplasmic reticulum membrane affect the mobilization of specific proteins.