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

Bojana Rakic, Selena M. Sagan, Matthew Noestheden, Sylvie Bélanger, Xiaolin Nan, Conor L. Evans, X. Sunney Xie, John Paul Pezacki

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Abstract

Hepatitis 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 PPARγ with RNA interference approaches had no effect on HCV replication in Huh-7 cells, whereas PPARα 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 PPARα. 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.

Original languageEnglish (US)
Pages (from-to)23-30
Number of pages8
JournalChemistry and Biology
Volume13
Issue number1
DOIs
StatePublished - Jan 1 2006

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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmacology
  • Drug Discovery
  • Clinical Biochemistry

Cite this

Rakic, B., Sagan, S. M., Noestheden, M., Bélanger, S., Nan, X., Evans, C. L., Xie, X. S., & Pezacki, J. P. (2006). Peroxisome proliferator-activated receptor α antagonism inhibits hepatitis C virus replication. Chemistry and Biology, 13(1), 23-30. https://doi.org/10.1016/j.chembiol.2005.10.006