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HCV 3a core protein increases lipid droplet cholesteryl ester content via a mechanism dependent on sphingolipid biosynthesis

Alfonso-Garcia, Alba
Conzelmann, Stéphanie
Potma, Eric O
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Published in PLOS ONE. 2014, vol. 9, no. 12, p. e115309
Abstract Hepatitis C virus (HCV) infected patients often develop steatosis and the HCV core protein alone can induce this phenomenon. To gain new insights into the pathways leading to steatosis, we performed lipidomic profiling of HCV core protein expressing-Huh-7 cells and also assessed the lipid profile of purified lipid droplets isolated from HCV 3a core expressing cells. Cholesteryl esters, ceramides and glycosylceramides, but not triglycerides, increased specifically in cells expressing the steatogenic HCV 3a core protein. Accordingly, inhibitors of cholesteryl ester biosynthesis such as statins and acyl-CoA cholesterol acyl transferase inhibitors prevented the increase of cholesteryl ester production and the formation of large lipid droplets in HCV core 3a-expressing cells. Furthermore, inhibition of de novo sphingolipid biosynthesis by myriocin - but not of glycosphingolipid biosynthesis by miglustat - affected both lipid droplet size and cholesteryl ester level. The lipid profile of purified lipid droplets, isolated from HCV 3a core-expressing cells, confirmed the particular increase of cholesteryl ester. Thus, both sphingolipid and cholesteryl ester biosynthesis are affected by the steatogenic core protein of HCV genotype 3a. These results may explain the peculiar lipid profile of HCV-infected patients with steatosis.
PMID: 25522003
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Research group Etudes et traitement de l'hépatite C et B (554)
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LOIZIDES-MANGOLD, Ursula et al. HCV 3a core protein increases lipid droplet cholesteryl ester content via a mechanism dependent on sphingolipid biosynthesis. In: PLOS ONE, 2014, vol. 9, n° 12, p. e115309. doi: 10.1371/journal.pone.0115309 https://archive-ouverte.unige.ch/unige:54993

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Deposited on : 2015-03-31

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