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Sci Rep. 2014 Apr 1;4:4549. doi: 10.1038/srep04549.

Stearoyl-CoA desaturase inhibition blocks formation of hepatitis C virus-induced specialized membranes.

Author information

1
1] National Research Council of Canada, Ottawa, Ontario, Canada [2] Department of Chemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Canada.
2
1] National Research Council of Canada, Ottawa, Ontario, Canada [2] Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Canada.
3
Merck Research Laboratories, Merck & Co., Kenilworth, N.J., USA.
4
National Research Council of Canada, Ottawa, Ontario, Canada.
5
1] Merck Research Laboratories, Merck & Co., Kenilworth, N.J., USA [2].
6
Immunology and Infectious Diseases, Faculty of Medicine, Memorial University of Newfoundland, St. John's, Newfoundland, Canada.
7
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.

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.

PMID:
25008545
PMCID:
PMC4091094
DOI:
10.1038/srep04549
[Indexed for MEDLINE]
Free PMC Article

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