Direct imaging of the disruption of hepatitis C virus replication complexes by inhibitors of lipid metabolism

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DOIResolve DOI: http://doi.org/10.1016/j.virol.2009.08.022
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TypeArticle
Journal titleVirology
Volume394
Issue1
Pages130142; # of pages: 12
SubjectHCV; Lovastatin; PPARalpha; Viral replication; CARS imaging
AbstractHere we have simultaneously characterized the influence of inhibitors of peroxisome proliferator-activated receptor α (PPARα) and the mevalonate pathway on hepatocyte lipid metabolism and the subcellular localization of hepatitis C virus (HCV) RNA using two-photon fluorescence (TPF) and coherent anti-Stokes Raman scattering (CARS) microscopy. Using this approach, we demonstrate that modulators of PPARα signaling rapidly cause the dispersion of HCV RNA from replication sites and simultaneously induce lipid storage and increases in lipid droplet size. We demonstrate that reductions in the levels of cholesterol resulting from inhibition of the mevalonate pathway upregulates triglyceride levels. We also show that the rate of dispersion of HCV RNA is very rapid when using a PPARα antagonist. This occurs with a faster rate to that of direct inhibition of 3-hydroxy-3-methyglutaryl CoA reductase (HMG-CoA reductase) using lovastatin in living cells, demonstrating the potential therapeutic value of modulating host cell pathways as part of a strategy to eliminate chronic HCV infection.
Publication date
LanguageEnglish
AffiliationNational Research Council Canada (NRC-CNRC); NRC Steacie Institute for Molecular Sciences
Peer reviewedYes
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This is a non-NRC publication

"Non-NRC publications" are publications authored by NRC employees prior to their employment by NRC.

NPARC number16080389
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Record identifier478e299b-ce78-490c-8985-5c6a2e488003
Record created2010-09-21
Record modified2016-05-09
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