Characterization of the inhibition of hepatitis C virus entry by in vitro-generated and patient-derived oxidized low-density lipoprotein.

2.50
Hdl Handle:
http://hdl.handle.net/10033/296837
Title:
Characterization of the inhibition of hepatitis C virus entry by in vitro-generated and patient-derived oxidized low-density lipoprotein.
Authors:
Westhaus, Sandra; Bankwitz, Dorothea; Ernst, Stefanie; Rohrmann, Katrin; Wappler, Ilka; Agné, Clemens; Luchtefeld, Maren; Schieffer, Bernhard; Sarrazin, Christoph; Manns, Michael P; Pietschmann, Thomas; Ciesek, Sandra; von Hahn, Thomas
Abstract:
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 antiviral 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 the 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 (scavenger receptor class B type I), but significantly earlier than anti-CD81, suggesting that oxLDL acts by perturbing 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. Conclusion: oxLDL is a potent pangenotype HCV entry inhibitor that maintains its activity in the context of human serum and targets an early step of HCV entry.
Affiliation:
Institute for Molecular Biology, Medizinische Hochschule Hannover, Hannover, Germany.
Citation:
Characterization of the inhibition of hepatitis C virus entry by in vitro-generated and patient-derived oxidized low-density lipoprotein. 2013, 57 (5):1716-24 Hepatology
Journal:
Hepatology (Baltimore, Md.)
Issue Date:
May-2013
URI:
http://hdl.handle.net/10033/296837
DOI:
10.1002/hep.26190
PubMed ID:
23212706
Type:
Article
Language:
en
ISSN:
1527-3350
Appears in Collections:
publications of the department experimental Virology([TC]EVIR)

Full metadata record

DC FieldValue Language
dc.contributor.authorWesthaus, Sandraen_GB
dc.contributor.authorBankwitz, Dorotheaen_GB
dc.contributor.authorErnst, Stefanieen_GB
dc.contributor.authorRohrmann, Katrinen_GB
dc.contributor.authorWappler, Ilkaen_GB
dc.contributor.authorAgné, Clemensen_GB
dc.contributor.authorLuchtefeld, Marenen_GB
dc.contributor.authorSchieffer, Bernharden_GB
dc.contributor.authorSarrazin, Christophen_GB
dc.contributor.authorManns, Michael Pen_GB
dc.contributor.authorPietschmann, Thomasen_GB
dc.contributor.authorCiesek, Sandraen_GB
dc.contributor.authorvon Hahn, Thomasen_GB
dc.date.accessioned2013-07-23T09:33:06Z-
dc.date.available2013-07-23T09:33:06Z-
dc.date.issued2013-05-
dc.identifier.citationCharacterization of the inhibition of hepatitis C virus entry by in vitro-generated and patient-derived oxidized low-density lipoprotein. 2013, 57 (5):1716-24 Hepatologyen_GB
dc.identifier.issn1527-3350-
dc.identifier.pmid23212706-
dc.identifier.doi10.1002/hep.26190-
dc.identifier.urihttp://hdl.handle.net/10033/296837-
dc.description.abstractOxidized 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 antiviral 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 the 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 (scavenger receptor class B type I), but significantly earlier than anti-CD81, suggesting that oxLDL acts by perturbing 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. Conclusion: oxLDL is a potent pangenotype HCV entry inhibitor that maintains its activity in the context of human serum and targets an early step of HCV entry.en_GB
dc.language.isoenen
dc.rightsArchived with thanks to Hepatology (Baltimore, Md.)en_GB
dc.subject.meshAntigens, CD36en_GB
dc.subject.meshCarcinoma, Hepatocellularen_GB
dc.subject.meshCell Line, Tumoren_GB
dc.subject.meshCells, Cultureden_GB
dc.subject.meshDNA, Viralen_GB
dc.subject.meshGenotypeen_GB
dc.subject.meshHepacivirusen_GB
dc.subject.meshHepatitis C, Chronicen_GB
dc.subject.meshHumansen_GB
dc.subject.meshLipoproteins, LDLen_GB
dc.subject.meshLiver Neoplasmsen_GB
dc.subject.meshViral Loaden_GB
dc.subject.meshVirionen_GB
dc.subject.meshVirus Replicationen_GB
dc.titleCharacterization of the inhibition of hepatitis C virus entry by in vitro-generated and patient-derived oxidized low-density lipoprotein.en
dc.typeArticleen
dc.contributor.departmentInstitute for Molecular Biology, Medizinische Hochschule Hannover, Hannover, Germany.en_GB
dc.identifier.journalHepatology (Baltimore, Md.)en_GB

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