Journal
VIROLOGY
Volume 394, Issue 1, Pages 130-142Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.virol.2009.08.022
Keywords
HCV; Lovastatin; PPARalpha; Viral replication; CARS imaging
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Funding
- Canadian Institutes for Health Research (CIHR)
- NSERC
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Here we have Simultaneously characterized the influence of inhibitors of peroxisome proliferator-activated receptor alpha (PPAR alpha) 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 PPAR alpha 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 PPAR alpha 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. Crown Copyright (C) 2009 Published by Elsevier Inc. All rights reserved.
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