کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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3314611 | 1211206 | 2007 | 10 صفحه PDF | دانلود رایگان |
Background/AimsHepatitis 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 resultsHCV-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 (Phe164) 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.ConclusionsThe 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.
Journal: Journal of Hepatology - Volume 46, Issue 6, June 2007, Pages 999–1008