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

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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Fatty Acids, Unsaturated / metabolism
  • Hepacivirus / drug effects
  • Hepacivirus / metabolism*
  • Humans
  • Membranes / drug effects
  • Membranes / metabolism*
  • Membranes / virology*
  • Stearoyl-CoA Desaturase / antagonists & inhibitors*
  • Stearoyl-CoA Desaturase / metabolism
  • Virus Replication / drug effects

Substances

  • Fatty Acids, Unsaturated
  • SCD1 protein, human
  • Stearoyl-CoA Desaturase