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dc.contributor.authorZapatero-Belinchón, Francisco J
dc.contributor.authorÖtjengerdes, Rina
dc.contributor.authorSheldon, Julie
dc.contributor.authorSchulte, Benjamin
dc.contributor.authorCarriquí-Madroñal, Belén
dc.contributor.authorBrogden, Graham
dc.contributor.authorArroyo-Fernández, Laura M
dc.contributor.authorVondran, Florian W R
dc.contributor.authorMaasoumy, Benjamin
dc.contributor.authorvon Hahn, Thomas
dc.contributor.authorGerold, Gisa
dc.date.accessioned2021-08-23T14:37:18Z
dc.date.available2021-08-23T14:37:18Z
dc.date.issued2021-06-29
dc.identifier.citationCells. 2021 Jun 29;10(7):1626. doi: 10.3390/cells10071626.en_US
dc.identifier.pmid34209751
dc.identifier.doi10.3390/cells10071626
dc.identifier.urihttp://hdl.handle.net/10033/622996
dc.description.abstractThe HCV replication cycle is tightly associated with host lipid metabolism: Lipoprotein receptors SR-B1 and LDLr promote entry of HCV, replication is associated with the formation of lipid-rich membranous organelles and infectious particle assembly highjacks the very‑low-density lipoprotein (VLDL) secretory pathway. Hence, medications that interfere with the lipid metabolism of the cell, such as statins, may affect HCV infection. Here, we study the interplay between lipoprotein receptors, lipid homeostasis, and HCV infection by genetic and pharmacological interventions. We found that individual ablation of the lipoprotein receptors SR‑B1 and LDLr did not drastically affect HCV entry, replication, or infection, but double lipoprotein receptor knock-outs significantly reduced HCV infection. Furthermore, we could show that this effect was neither due to altered expression of additional HCV entry factors nor caused by changes in cellular cholesterol content. Strikingly, whereas lipid‑lowering drugs such as simvastatin or fenofibrate did not affect HCV entry or infection of immortalized hepatoma cells expressing SR-B1 and/or LDLr or primary human hepatocytes, ablation of these receptors rendered cells more susceptible to these drugs. Finally, we observed no significant differences between statin users and control groups with regards to HCV viral load in a cohort of HCV infected patients before and during HCV antiviral treatment. Interestingly, statin treatment, which blocks the mevalonate pathway leading to decreased cholesterol levels, was associated with mild but appreciable lower levels of liver damage markers before HCV therapy. Overall, our findings confirm the role of lipid homeostasis in HCV infection and highlight the importance of the mevalonate pathway in the HCV replication cycle.en_US
dc.language.isoenen_US
dc.publisherMDPIen_US
dc.rightsAttribution 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subjectHCVen_US
dc.subjectHMG-CoA-reductase inhibitoren_US
dc.subjectLDLren_US
dc.subjectPCSK9‑inhibitoren_US
dc.subjectSR-B1en_US
dc.subjectfibrateen_US
dc.subjecthepatitis C virusen_US
dc.subjectlipid metabolismen_US
dc.subjectlipid-lowering drugen_US
dc.subjectlipoprotein receptoren_US
dc.subjectstatinen_US
dc.titleInterdependent Impact of Lipoprotein Receptors and Lipid-Lowering Drugs on HCV Infectivity.en_US
dc.typeArticleen_US
dc.identifier.eissn2073-4409
dc.contributor.departmentTWINCORE, Zentrum für experimentelle und klinische Infektionsforschung GmbH,Feodor-Lynen Str. 7, 30625 Hannover, Germany.en_US
dc.identifier.journalCellsen_US
dc.source.volume10
dc.source.issue7
dc.source.journaltitleCells
dc.source.countrySwitzerland


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Attribution 4.0 International
Except where otherwise noted, this item's license is described as Attribution 4.0 International