Lipid Metabolite Profiling Identifies Desmosterol Metabolism As a New Antiviral Target for Hepatitis C Virus

Overview

Journal J Am Chem Soc

Publisher American Chemical Society

Specialty Chemistry

Date 2012 Apr 7

PMID 22480142

Citations 21

Authors

Mary A Rodgers

Valerie A Villareal

Esperance A Schaefer

Lee F Peng

Kathleen E Corey

Raymond T Chung

Priscilla L Yang

Affiliations

Soon will be listed here.

Abstract

Hepatitis C virus (HCV) infection has been clinically associated with serum lipid abnormalities, yet our understanding of the effects of HCV on host lipid metabolism and conversely the function of individual lipids in HCV replication remains incomplete. Using liquid chromatography-mass spectrometry metabolite profiling of the HCV JFH1 cell culture infection model, we identified a significant steady-state accumulation of desmosterol, an immediate precursor to cholesterol. Pharmacological inhibition or RNAi-mediated depletion of DHCR7 significantly reduced steady-state HCV protein expression and viral genomic RNA. Moreover, this effect was reversed when cultures were supplemented with exogenous desmosterol. Together, these observations suggest an intimate connection between HCV replication and desmosterol homeostasis and that the enzymes responsible for synthesis of desmosterol may be novel targets for antiviral design.

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