Lipid metabolite profiling identifies desmosterol metabolism as a new antiviral target for hepatitis C virus.
J Am Chem Soc
; 134(16): 6896-9, 2012 Apr 25.
Article
em En
| MEDLINE
| ID: mdl-22480142
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Antivirais
/
Hepatite C
/
Hepacivirus
/
Desmosterol
/
Metabolismo dos Lipídeos
Limite:
Humans
Idioma:
En
Revista:
J Am Chem Soc
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
Estados Unidos