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J Hepatol. 2007 Jun;46(6):999-1008. Epub 2006 Nov 27.

Up-regulation of fatty acid synthase promoter by hepatitis C virus core protein: genotype-3a core has a stronger effect than genotype-1b core.

Author information

1
Vaccine and Infectious Disease Organization, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.

Abstract

BACKGROUND/AIMS:

Hepatitis C virus genotype-3a (HCV-3a) is directly linked to steatosis development. We studied the effects of HCV-3a core protein on the promoter activity of fatty acid synthase (FAS), a major enzyme involved in de novo lipid synthesis.

METHODS AND RESULTS:

HCV-3a and -1b core genes were cloned and expressed. Using a FAS promoter-luciferase reporter, we demonstrated that both HCV-3a and -1b core proteins up-regulated the FAS promoter. However, HCV-3a core protein expression induced significantly higher FAS promoter activity than HCV-1b core. We further showed that FAS up-regulation by HCV core was dependent on transcription factor sterol response element binding protein-1. Mutational analysis showed that processing of HCV core protein of different genotypes was differentially involved in FAS promoter up-regulation. Although lipid droplet localization of HCV core protein was not important for FAS up-regulation, a specific amino acid residue (Phe(164)) within the FATG lipid droplet localization sequence of HCV-3a core protein played a major role in the stronger FAS activation by HCV-3a core.

CONCLUSIONS:

The stronger effect of HCV-3a core protein on FAS activation in comparison to HCV-1b core could contribute to the higher prevalence and severity of steatosis in HCV-3a infections.

PMID:
17188392
DOI:
10.1016/j.jhep.2006.10.019
[Indexed for MEDLINE]

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