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

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Year: 2008 Volume: 47 Issue: 4

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

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Nahmias, Yaakov Goldwasser, Jonathan Casali, Monica Van Poll, Daan Wakita, Takaji Chung, Raymond T. Yarmush, Martin L.
Description	Country affiliation: United States Author Affiliation: Nahmias Y ( Center for Engineering in Medicine, Shriners Burns Hospital, Boston, MA, USA. ynahmias@partners.org)
Abstract	UNLABELLED: 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.
File Format	HTM / HTML
ISSN	02709139
e-ISSN	15273350
DOI	10.1002/hep.22197
Journal	Hepatology
Issue Number	5
Volume Number	47
Language	English
Publisher	Wiley
Publisher Date	2008-05-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Discipline Hepatology Apolipoproteins B Physiology Flavanones Pharmacology Gene Silencing Hepacivirus Genetics Carcinoma, Hepatocellular Virology Cell Line, Tumor Cell Survival Citrus Paradisi Dna Primers Enzyme-linked Immunosorbent Assay Drug Effects Pathogenicity Liver Neoplasms Rna, Messenger Reverse Transcriptase Polymerase Chain Reaction Viral Core Proteins
Content Type	Text
Resource Type	Article
Subject	Hepatology

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Apolipoprotein B–Dependent Hepatitis C Virus Secretion Is Inhibited by the Grapefruit Flavonoid Naringenin

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

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