{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T19:31:53Z","timestamp":1778873513712,"version":"3.51.4"},"reference-count":72,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2021,6,29]],"date-time":"2021-06-29T00:00:00Z","timestamp":1624924800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["158989968"],"award-info":[{"award-number":["158989968"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"name":"SFB 900","award":["C7"],"award-info":[{"award-number":["C7"]}]},{"DOI":"10.13039\/501100004063","name":"Knut and Alice Wallenberg Foundation","doi-asserted-by":"publisher","award":["-"],"award-info":[{"award-number":["-"]}],"id":[{"id":"10.13039\/501100004063","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>The 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.<\/jats:p>","DOI":"10.3390\/cells10071626","type":"journal-article","created":{"date-parts":[[2021,6,29]],"date-time":"2021-06-29T10:52:46Z","timestamp":1624963966000},"page":"1626","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Interdependent Impact of Lipoprotein Receptors and Lipid-Lowering Drugs on HCV Infectivity"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2751-8411","authenticated-orcid":false,"given":"Francisco J.","family":"Zapatero-Belinch\u00f3n","sequence":"first","affiliation":[{"name":"Centre for Experimental and Clinical Infection Research, Institute for Experimental Virology, TWINCORE, 30625 Hannover, Germany"},{"name":"Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, 30625 Hannover, Germany"},{"name":"Institute of Molecular Biology, Hannover Medical School, 30625 Hannover, Germany"},{"name":"German Center for Infection Research (DZIF), Hannover-Braunschweig Site, 38124 Braunschweig, Germany"},{"name":"Department of Clinical Microbiology, Virology, Ume\u00e5 University, SE-90185 Ume\u00e5, Sweden"},{"name":"Wallenberg Centre for Molecular Medicine (WCMM), Ume\u00e5 University, SE-90185 Ume\u00e5, Sweden"},{"name":"Department of Biochemistry & Research Center for Emerging Infections and Zoonoses (RIZ), University of Veterinary Medicine Hannover, 30559 Hannover, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rina","family":"\u00d6tjengerdes","sequence":"additional","affiliation":[{"name":"Centre for Experimental and Clinical Infection Research, Institute for Experimental Virology, TWINCORE, 30625 Hannover, Germany"},{"name":"Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, 30625 Hannover, Germany"},{"name":"Institute of Molecular Biology, Hannover Medical School, 30625 Hannover, Germany"},{"name":"German Center for Infection Research (DZIF), Hannover-Braunschweig Site, 38124 Braunschweig, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julie","family":"Sheldon","sequence":"additional","affiliation":[{"name":"Centre for Experimental and Clinical Infection Research, Institute for Experimental Virology, TWINCORE, 30625 Hannover, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0380-5985","authenticated-orcid":false,"given":"Benjamin","family":"Schulte","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, 30625 Hannover, Germany"},{"name":"German Center for Infection Research (DZIF), Hannover-Braunschweig Site, 38124 Braunschweig, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bel\u00e9n","family":"Carriqu\u00ed-Madro\u00f1al","sequence":"additional","affiliation":[{"name":"Centre for Experimental and Clinical Infection Research, Institute for Experimental Virology, TWINCORE, 30625 Hannover, Germany"},{"name":"Department of Biochemistry & Research Center for Emerging Infections and Zoonoses (RIZ), University of Veterinary Medicine Hannover, 30559 Hannover, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Graham","family":"Brogden","sequence":"additional","affiliation":[{"name":"Centre for Experimental and Clinical Infection Research, Institute for Experimental Virology, TWINCORE, 30625 Hannover, Germany"},{"name":"Department of Biochemistry & Research Center for Emerging Infections and Zoonoses (RIZ), University of Veterinary Medicine Hannover, 30559 Hannover, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0698-1132","authenticated-orcid":false,"given":"Laura M.","family":"Arroyo-Fern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Department of Biochemistry & Research Center for Emerging Infections and Zoonoses (RIZ), University of Veterinary Medicine Hannover, 30559 Hannover, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Florian W. R.","family":"Vondran","sequence":"additional","affiliation":[{"name":"German Center for Infection Research (DZIF), Hannover-Braunschweig Site, 38124 Braunschweig, Germany"},{"name":"Department of General, Visceral and Transplant Surgery, Hannover Medical School, 30625 Hannover, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Benjamin","family":"Maasoumy","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, 30625 Hannover, Germany"},{"name":"German Center for Infection Research (DZIF), Hannover-Braunschweig Site, 38124 Braunschweig, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"von Hahn","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, 30625 Hannover, Germany"},{"name":"Department of Gastroenterology, Hepatology and Interventional Endoscopy, Asklepios Hospital Barmbek, Semmelweis University, Campus Hamburg, 22307 Hamburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1326-5038","authenticated-orcid":false,"given":"Gisa","family":"Gerold","sequence":"additional","affiliation":[{"name":"Centre for Experimental and Clinical Infection Research, Institute for Experimental Virology, TWINCORE, 30625 Hannover, Germany"},{"name":"Department of Clinical Microbiology, Virology, Ume\u00e5 University, SE-90185 Ume\u00e5, Sweden"},{"name":"Wallenberg Centre for Molecular Medicine (WCMM), Ume\u00e5 University, SE-90185 Ume\u00e5, Sweden"},{"name":"Department of Biochemistry & Research Center for Emerging Infections and Zoonoses (RIZ), University of Veterinary Medicine Hannover, 30559 Hannover, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,6,29]]},"reference":[{"key":"ref_1","unstructured":"(2020, June 26). 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