Lipid metabolite profiling identifies desmosterol metabolism as a new antiviral target for hepatitis C virus.

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 a

SUBMITTER: Rodgers MA 

PROVIDER: S-EPMC3375380 | biostudies-literature | 2012 Apr

REPOSITORIES: biostudies-literature