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

Research output: Contribution to journalArticle

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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 2006
Externally publishedYes

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Peroxisome Proliferator-Activated Receptors
Virus Replication
Viruses
Hepacivirus
Down-Regulation
RNA
Replicon
Raman Spectrum Analysis
Medical problems
RNA Interference
Lipid Metabolism
Liver
Raman scattering
Liver Diseases
Microscopy
Phospholipids
Microscopic examination
Triglycerides
Fluorescence
Cholesterol

ASJC Scopus subject areas

  • Organic Chemistry

Cite this

Rakic, B., Sagan, S. M., Noestheden, M., Bélanger, S., Nan, X., Evans, C. L., ... 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

Peroxisome proliferator-activated receptor α antagonism inhibits hepatitis C virus replication. / Rakic, Bojana; Sagan, Selena M.; Noestheden, Matthew; Bélanger, Sylvie; Nan, Xiaolin; Evans, Conor L.; Xie, X. Sunney; Pezacki, John Paul.

In: Chemistry and Biology, Vol. 13, No. 1, 01.2006, p. 23-30.

Research output: Contribution to journalArticle

Rakic, B, Sagan, SM, Noestheden, M, Bélanger, S, Nan, X, Evans, CL, Xie, XS & Pezacki, JP 2006, 'Peroxisome proliferator-activated receptor α antagonism inhibits hepatitis C virus replication', Chemistry and Biology, vol. 13, no. 1, pp. 23-30. https://doi.org/10.1016/j.chembiol.2005.10.006
Rakic, Bojana ; Sagan, Selena M. ; Noestheden, Matthew ; Bélanger, Sylvie ; Nan, Xiaolin ; Evans, Conor L. ; Xie, X. Sunney ; Pezacki, John Paul. / Peroxisome proliferator-activated receptor α antagonism inhibits hepatitis C virus replication. In: Chemistry and Biology. 2006 ; Vol. 13, No. 1. pp. 23-30.
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