title: Stearoyl-CoA desaturase inhibition blocks formation of hepatitis C virus-induced specialized membranes.
abstract: Hepatitis C virus (HCV) replication is dependent on the formation of specialized membrane structures; however, the host factor requirements for the formation of these HCV complexes remain unclear. Herein, we demonstrate that inhibition of stearoyl-CoA desaturase 1 (SCD-1) halts the biosynthesis of unsaturated fatty acids, such as oleic acid, and negatively modulates HCV replication. Unsaturated fatty acids play key roles in membrane curvature and fluidity. Mechanistically, we demonstrate that SCD-1 inhibition disrupts the integrity of membranous HCV replication complexes and renders HCV RNA susceptible to nuclease-mediated degradation. Our work establishes a novel function for unsaturated fatty acids in HCV replication.
authors.affiliation: 1] National Research Council of Canada, Ottawa, Ontario, Canada [2] Department of Chemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Canada.
authors.forename: Rodney K
authors.initials: RK
authors.lastname: Lyn
authors.affiliation: 1] National Research Council of Canada, Ottawa, Ontario, Canada [2] Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Canada.
authors.forename: Ragunath
authors.initials: R
authors.lastname: Singaravelu
authors.affiliation: Merck Research Laboratories, Merck & Co., Kenilworth, N.J., USA.
authors.forename: Stacia
authors.initials: S
authors.lastname: Kargman
authors.affiliation: National Research Council of Canada, Ottawa, Ontario, Canada.
authors.forename: Shifawn
authors.initials: S
authors.lastname: O'Hara
authors.affiliation: 1] Merck Research Laboratories, Merck & Co., Kenilworth, N.J., USA [2].
authors.forename: Helen
authors.initials: H
authors.lastname: Chan
authors.affiliation: 1] Merck Research Laboratories, Merck & Co., Kenilworth, N.J., USA [2].
authors.forename: Renata
authors.initials: R
authors.lastname: Oballa
authors.affiliation: 1] Merck Research Laboratories, Merck & Co., Kenilworth, N.J., USA [2].
authors.forename: Zheng
authors.initials: Z
authors.lastname: Huang
authors.affiliation: Immunology and Infectious Diseases, Faculty of Medicine, Memorial University of Newfoundland, St. John's, Newfoundland, Canada.
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Jones
authors.affiliation: National Research Council of Canada, Ottawa, Ontario, Canada.
authors.forename: Andrew
authors.initials: A
authors.lastname: Ridsdale
authors.affiliation: Immunology and Infectious Diseases, Faculty of Medicine, Memorial University of Newfoundland, St. John's, Newfoundland, Canada.
authors.forename: Rodney S
authors.initials: RS
authors.lastname: Russell
authors.affiliation: 1] Merck Research Laboratories, Merck & Co., Kenilworth, N.J., USA [2].
authors.forename: Anthony W
authors.initials: AW
authors.lastname: Partridge
authors.affiliation: 1] National Research Council of Canada, Ottawa, Ontario, Canada [2] Department of Chemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Canada [3] Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Canada.
authors.forename: John Paul
authors.initials: JP
authors.lastname: Pezacki
mesh_terms: D045744:Cell Line, Tumor; D005231:Fatty Acids, Unsaturated / Q000378:metabolism; D016174:Hepacivirus / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D008566:Membranes / Q000187:drug effects / Q000378:metabolism* / Q000821:virology*; D013230:Stearoyl-CoA Desaturase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014779:Virus Replication / Q000187:drug effects
chemical_list: D005231:Fatty Acids, Unsaturated; C523776:SCD1 protein, human; D013230:Stearoyl-CoA Desaturase