Apolipoprotein B-dependent hepatitis C virus secretion is inhibited by the grapefruit flavonoid naringenin

Center for Engineering in Medicine, Shriners Burns Hospital, Boston, MA, USA.
Hepatology (Impact Factor: 11.06). 05/2008; 47(5):1437-45. DOI: 10.1002/hep.22197
Source: PubMed


Hepatitis C virus (HCV) infects over 3% of the world population and is the leading cause of chronic liver disease worldwide. HCV has long been known to associate with circulating lipoproteins, and its interactions with the cholesterol and lipid pathways have been recently described. In this work, we demonstrate that HCV is actively secreted by infected cells through a Golgi-dependent mechanism while bound to very low density lipoprotein (vLDL). Silencing apolipoprotein B (ApoB) messenger RNA in infected cells causes a 70% reduction in the secretion of both ApoB-100 and HCV. More importantly, we demonstrate that the grapefruit flavonoid naringenin, previously shown to inhibit vLDL secretion both in vivo and in vitro, inhibits the microsomal triglyceride transfer protein activity as well as the transcription of 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase and acyl-coenzyme A:cholesterol acyltransferase 2 in infected cells. Stimulation with naringenin reduces HCV secretion in infected cells by 80%. Moreover, we find that naringenin is effective at concentrations that are an order of magnitude below the toxic threshold in primary human hepatocytes and in mice. CONCLUSION: These results suggest a novel therapeutic approach for the treatment of HCV infection.

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Available from: Yaakov Nahmias, Apr 10, 2015
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    • "HCV core protein and ApoB100 in culture supernatants were measured using Ortho Ò HCV core antigen ELISA (Wako Chemicals) and Alerchek's Human ApoB100 ELISA, respectively, as previously described [15]. "

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    • "Few of the plant derived dietary components have been explored for their abilities to interfere with all possible stages of HCV life cycle via different mechanisms and proved valuable to HCV therapy. Recently, naringenin (grapes) has been shown to inhibit apolipoprotein B-dependent secretion of HCV particles5. Proanthocyanidin (blueberry) suppresses HCV replication, possibly by interacting with hnRNP A2/B6. "
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