Peroxisome proliferator-activated receptor α antagonism inhibits hepatitis C virus replication

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DOIResolve DOI: http://doi.org/10.1016/j.chembiol.2005.10.006
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TypeArticle
Journal titleChemistry & Biology
Volume13
Issue1
Pages2330; # of pages: 8
AbstractHepatitis C virus (HCV) is a global health problem and a leading cause of liver disease. Here, we demonstrate that the replication of HCV replicon RNA in Huh-7 cells is inhibited by a peroxisome proliferator-activated receptor (PPAR) antagonist, 2-chloro-5-nitro-N-(pyridyl)benzamide (BA). Downregulation of PPAR[gamma] with RNA interference approaches had no effect on HCV replication in Huh-7 cells, whereas PPAR[alpha] downregulation inhibited HCV replication. Fluorescence and coherent anti-Stokes Raman scattering (CARS) microscopy demonstrate a clear buildup of lipids upon treatment with BA. These observations are consistent with the misregulation of lipid metabolism, phospholipid secretion, cholesterol catabolism, and triglyceride clearance events associated with the inhibition of PPAR[alpha]. The inhibition of HCV replication by BA may result from disrupting lipidation of host proteins associated with the HCV replication complex or, more generally, by disrupting the membranous web where HCV replicates.
Publication date
LanguageEnglish
AffiliationNational Research Council Canada; NRC Steacie Institute for Molecular Sciences
Peer reviewedNo
NPARC number12338300
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Record identifierc1e9d7e8-0541-4e46-a9fb-72a6edb67ef0
Record created2009-09-10
Record modified2016-05-09
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