Document Detail


Characterization of the inhibition of hepatitis C virus entry by in vitro generated and patient derived oxidized low density lipoprotein.
MedLine Citation:
PMID:  23212706     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Oxidized low density lipoprotein (oxLDL) has been reported as an inhibitor of hepatitis C virus (HCV) cell entry making it the only known component of human lipid metabolism with an anti-viral effect on HCV. However, several questions remain open including its effect on full length cell culture grown HCV (HCVcc) of different genotypes or on other steps of the viral replication cycle, its mechanism of action and whether endogenous oxLDL shares the anti-HCV properties of in vitro generated oxLDL. We combined molecular virology tools with oxLDL serum measurements in different patient cohorts to address these questions. We found that oxLDL inhibits HCVcc at least as potently as HCV pseudoparticles. There was moderate variation between genotypes with genotype 4 appearing most oxLDL sensitive. Intracellular RNA replication and assembly and release of new particles were unaffected. HCV particles entering target cells lost oxLDL sensitivity with time kinetics parallel to anti-SR-BI but significantly earlier than anti-CD81 suggesting that oxLDL acts by perturbing the interaction between HCV and SR-BI. Finally, in chronically HCV infected individuals endogenous serum oxLDL levels did not correlate with viral load, but in HCV-negative sera high endogenous oxLDL had a negative effect on HCV infectivity in vitro. In conclusion oxLDL is a potent pan-genotype HCV entry inhibitor that maintains its activity in the context of human serum and targets an early step of HCV entry. (HEPATOLOGY 2012.).
Authors:
Sandra Westhaus; Dorothea Bankwitz; Stefanie Ernst; Katrin Rohrmann; Ilka Wappler; Clemens Agné; Maren Luchtefeld; Bernhard Schieffer; Christoph Sarrazin; Michael P Manns; Thomas Pietschmann; Sandra Ciesek; Thomas von Hahn
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-12-5
Journal Detail:
Title:  Hepatology (Baltimore, Md.)     Volume:  -     ISSN:  1527-3350     ISO Abbreviation:  Hepatology     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-12-5     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8302946     Medline TA:  Hepatology     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012 American Association for the Study of Liver Diseases.
Affiliation:
Institute for Molecular Biology, Medizinische Hochschule Hannover, Hannover, Germany; Department of Gastroenterology, Hepatology and Endocrinology, Medizinische Hochschule Hannover, Hannover, Germany.
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