The hepatitis C virus core protein inhibits adipose triglyceride lipase (ATGL)-mediated lipid mobilization and enhances the ATGL interaction with comparative gene identification 58 (CGI-58) and lipid droplets. 2014

Gregory Camus, and Martina Schweiger, and Eva Herker, and Charles Harris, and Andrew S Kondratowicz, and Chia-Lin Tsou, and Robert V Farese, and Kithsiri Herath, and Stephen F Previs, and Thomas P Roddy, and Shirly Pinto, and Rudolf Zechner, and Melanie Ott
From the Gladstone Institute of Virology and Immunology, San Francisco, California 94158.

Liver steatosis is a common health problem associated with hepatitis C virus (HCV) and an important risk factor for the development of liver fibrosis and cancer. Steatosis is caused by triglycerides (TG) accumulating in lipid droplets (LDs), cellular organelles composed of neutral lipids surrounded by a monolayer of phospholipids. The HCV nucleocapsid core localizes to the surface of LDs and induces steatosis in cultured cells and mouse livers by decreasing intracellular TG degradation (lipolysis). Here we report that core at the surface of LDs interferes with the activity of adipose triglyceride lipase (ATGL), the key lipolytic enzyme in the first step of TG breakdown. Expressing core in livers or mouse embryonic fibroblasts of ATGL(-/-) mice no longer decreases TG degradation as observed in LDs from wild-type mice, supporting the model that core reduces lipolysis by engaging ATGL. Core must localize at LDs to inhibit lipolysis, as ex vivo TG hydrolysis is impaired in purified LDs coated with core but not when free core is added to LDs. Coimmunoprecipitation experiments revealed that core does not directly interact with the ATGL complex but, unexpectedly, increased the interaction between ATGL and its activator CGI-58 as well as the recruitment of both proteins to LDs. These data link the anti-lipolytic activity of the HCV core protein with altered ATGL binding to CGI-58 and the enhanced association of both proteins with LDs.

UI MeSH Term Description Entries
D008049 Lipase An enzyme of the hydrolase class that catalyzes the reaction of triacylglycerol and water to yield diacylglycerol and a fatty acid anion. It is produced by glands on the tongue and by the pancreas and initiates the digestion of dietary fats. (From Dorland, 27th ed) EC 3.1.1.3. Triacylglycerol Lipase,Tributyrinase,Triglyceride Lipase,Acid Lipase,Acid Lipase A,Acid Lipase B,Acid Lipase I,Acid Lipase II,Exolipase,Monoester Lipase,Triacylglycerol Hydrolase,Triglyceridase,Triolean Hydrolase,Hydrolase, Triacylglycerol,Hydrolase, Triolean,Lipase A, Acid,Lipase B, Acid,Lipase I, Acid,Lipase II, Acid,Lipase, Acid,Lipase, Monoester,Lipase, Triglyceride
D008297 Male Males
D008810 Mice, Inbred C57BL One of the first INBRED MOUSE STRAINS to be sequenced. This strain is commonly used as genetic background for transgenic mouse models. Refractory to many tumors, this strain is also preferred model for studying role of genetic variations in development of diseases. Mice, C57BL,Mouse, C57BL,Mouse, Inbred C57BL,C57BL Mice,C57BL Mice, Inbred,C57BL Mouse,C57BL Mouse, Inbred,Inbred C57BL Mice,Inbred C57BL Mouse
D002522 Chlorocebus aethiops A species of CERCOPITHECUS containing three subspecies: C. tantalus, C. pygerythrus, and C. sabeus. They are found in the forests and savannah of Africa. The African green monkey is the natural host of SIMIAN IMMUNODEFICIENCY VIRUS and is used in AIDS research. African Green Monkey,Cercopithecus aethiops,Cercopithecus griseoviridis,Cercopithecus griseus,Cercopithecus pygerythrus,Cercopithecus sabeus,Cercopithecus tantalus,Chlorocebus cynosuros,Chlorocebus cynosurus,Chlorocebus pygerythrus,Green Monkey,Grivet Monkey,Lasiopyga weidholzi,Malbrouck,Malbrouck Monkey,Monkey, African Green,Monkey, Green,Monkey, Grivet,Monkey, Vervet,Savanah Monkey,Vervet Monkey,Savannah Monkey,African Green Monkey,Chlorocebus cynosuro,Green Monkey, African,Green Monkeys,Grivet Monkeys,Malbrouck Monkeys,Malbroucks,Monkey, Malbrouck,Monkey, Savanah,Monkey, Savannah,Savannah Monkeys,Vervet Monkeys
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D006868 Hydrolysis The process of cleaving a chemical compound by the addition of a molecule of water.
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D014280 Triglycerides An ester formed from GLYCEROL and three fatty acid groups. Triacylglycerol,Triacylglycerols,Triglyceride
D014758 Viral Core Proteins Proteins found mainly in icosahedral DNA and RNA viruses. They consist of proteins directly associated with the nucleic acid inside the NUCLEOCAPSID. Core Proteins, Viral,Major Core Protein,Major Core Proteins, Viral,Adenovirus Core Protein VII,Core Protein V,Core Protein lambda 2,Influenza Virus Core Proteins,Major Core Protein lambda 1,Major Core Protein lambda-1,Major Core Protein sigma 2,Major Core Protein sigma-2,OVP 19,Oncornaviral Protein P19,P30 Core Proteins,Viral Protein P19,Virus Core Proteins,Core Protein, Major,Core Proteins, P30,Core Proteins, Virus,Protein P19, Oncornaviral,Protein P19, Viral,Protein, Major Core,Proteins, P30 Core,Proteins, Viral Core,Proteins, Virus Core
D045744 Cell Line, Tumor A cell line derived from cultured tumor cells. Tumor Cell Line,Cell Lines, Tumor,Line, Tumor Cell,Lines, Tumor Cell,Tumor Cell Lines

Related Publications

Gregory Camus, and Martina Schweiger, and Eva Herker, and Charles Harris, and Andrew S Kondratowicz, and Chia-Lin Tsou, and Robert V Farese, and Kithsiri Herath, and Stephen F Previs, and Thomas P Roddy, and Shirly Pinto, and Rudolf Zechner, and Melanie Ott
April 2010, The Journal of biological chemistry,
Gregory Camus, and Martina Schweiger, and Eva Herker, and Charles Harris, and Andrew S Kondratowicz, and Chia-Lin Tsou, and Robert V Farese, and Kithsiri Herath, and Stephen F Previs, and Thomas P Roddy, and Shirly Pinto, and Rudolf Zechner, and Melanie Ott
January 2012, Adipocyte,
Gregory Camus, and Martina Schweiger, and Eva Herker, and Charles Harris, and Andrew S Kondratowicz, and Chia-Lin Tsou, and Robert V Farese, and Kithsiri Herath, and Stephen F Previs, and Thomas P Roddy, and Shirly Pinto, and Rudolf Zechner, and Melanie Ott
October 2010, Molecular biology reports,
Gregory Camus, and Martina Schweiger, and Eva Herker, and Charles Harris, and Andrew S Kondratowicz, and Chia-Lin Tsou, and Robert V Farese, and Kithsiri Herath, and Stephen F Previs, and Thomas P Roddy, and Shirly Pinto, and Rudolf Zechner, and Melanie Ott
December 2023, Journal of lipid research,
Gregory Camus, and Martina Schweiger, and Eva Herker, and Charles Harris, and Andrew S Kondratowicz, and Chia-Lin Tsou, and Robert V Farese, and Kithsiri Herath, and Stephen F Previs, and Thomas P Roddy, and Shirly Pinto, and Rudolf Zechner, and Melanie Ott
January 2007, Medecine sciences : M/S,
Gregory Camus, and Martina Schweiger, and Eva Herker, and Charles Harris, and Andrew S Kondratowicz, and Chia-Lin Tsou, and Robert V Farese, and Kithsiri Herath, and Stephen F Previs, and Thomas P Roddy, and Shirly Pinto, and Rudolf Zechner, and Melanie Ott
April 2015, International journal of molecular sciences,
Gregory Camus, and Martina Schweiger, and Eva Herker, and Charles Harris, and Andrew S Kondratowicz, and Chia-Lin Tsou, and Robert V Farese, and Kithsiri Herath, and Stephen F Previs, and Thomas P Roddy, and Shirly Pinto, and Rudolf Zechner, and Melanie Ott
March 2008, Journal of viral hepatitis,
Gregory Camus, and Martina Schweiger, and Eva Herker, and Charles Harris, and Andrew S Kondratowicz, and Chia-Lin Tsou, and Robert V Farese, and Kithsiri Herath, and Stephen F Previs, and Thomas P Roddy, and Shirly Pinto, and Rudolf Zechner, and Melanie Ott
July 2010, Cell cycle (Georgetown, Tex.),
Gregory Camus, and Martina Schweiger, and Eva Herker, and Charles Harris, and Andrew S Kondratowicz, and Chia-Lin Tsou, and Robert V Farese, and Kithsiri Herath, and Stephen F Previs, and Thomas P Roddy, and Shirly Pinto, and Rudolf Zechner, and Melanie Ott
May 2013, Yi chuan = Hereditas,
Gregory Camus, and Martina Schweiger, and Eva Herker, and Charles Harris, and Andrew S Kondratowicz, and Chia-Lin Tsou, and Robert V Farese, and Kithsiri Herath, and Stephen F Previs, and Thomas P Roddy, and Shirly Pinto, and Rudolf Zechner, and Melanie Ott
January 2015, PloS one,
Copied contents to your clipboard!