{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T13:50:32Z","timestamp":1790344232603,"version":"4.1.0"},"reference-count":121,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2021,4,27]],"date-time":"2021-04-27T00:00:00Z","timestamp":1619481600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Metabolites"],"abstract":"<jats:p>Lipids and lipoproteins constitute indispensable components for living not only for humans. In the case of hepatitis C virus (HCV), the option of using the products of our lipid metabolism is \u201cto be, or not to be\u201d. On the other hand, HCV infection, which is the main cause of chronic hepatitis, cirrhosis and hepatocellular carcinoma, exerts a profound influence on lipid and lipoprotein metabolism of the host. The consequences of this alternation are frequently observed as hypolipidemia and hepatic steatosis in chronic hepatitis C (CHC) patients. The clinical relevance of these changes reflects the fact that lipids and lipoprotein play a crucial role in all steps of the life cycle of HCV. The virus circulates in the bloodstream as a highly lipidated lipo-viral particle (LVP) that defines HCV hepatotropism. Thus, strict relationships between lipids\/lipoproteins and HCV are indispensable for the mechanism of viral entry into hepatocytes, viral replication, viral particles assembly and secretion. The purpose of this review is to summarize the tricks thanks to which HCV utilizes host lipid metabolism to its own advantage.<\/jats:p>","DOI":"10.3390\/metabo11050273","type":"journal-article","created":{"date-parts":[[2021,4,27]],"date-time":"2021-04-27T06:19:11Z","timestamp":1619504351000},"page":"273","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["Hepatitis C Virus Uses Host Lipids to Its Own Advantage"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6620-4450","authenticated-orcid":false,"given":"Malgorzata","family":"Sidorkiewicz","sequence":"first","affiliation":[{"name":"Department of Medical Biochemistry, Faculty of Health Sciences, Medical University of Lodz, 90-419 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,4,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1451","DOI":"10.1016\/S0140-6736(19)32320-7","article-title":"Hepatitis C","volume":"394","author":"Spearman","year":"2019","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1016\/j.jhep.2009.08.004","article-title":"The long and winding road leading to the identification of the hepatitis C virus","volume":"51","author":"Houghton","year":"2009","journal-title":"J. Hepatol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1126\/science.1114016","article-title":"Complete replication of hepatitis C virus in cell culture","volume":"309","author":"Lindenbach","year":"2005","journal-title":"Science"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"9294","DOI":"10.1073\/pnas.0503596102","article-title":"Robust hepatitis C virus infection in vitro","volume":"102","author":"Zhong","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1038\/nature14899","article-title":"SEC14L2 enables pan-genotype HCV replication in cell culture","volume":"524","author":"Saeed","year":"2015","journal-title":"Nature"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"101596","DOI":"10.1016\/j.clinre.2020.101596","article-title":"Epidemiology of hepatitis C virus infection","volume":"45","year":"2021","journal-title":"Clin. Res. Hepatol. Gastroenterol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1007\/s15010-019-01345-y","article-title":"Epidemiological and etiological variations in hepatocellular carcinoma","volume":"48","author":"Sagnelli","year":"2020","journal-title":"Infection"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1175","DOI":"10.1136\/jcp.34.10.1175","article-title":"Clinical and histological features of a group of patients with sporadic non-A, non-B hepatitis","volume":"34","author":"Bamber","year":"1981","journal-title":"J. Clin. Pathol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/S0009-8981(97)06532-7","article-title":"Blood lipids of patients with chronic hepatitis: Differences related to viral etiology","volume":"261","author":"Fabris","year":"1997","journal-title":"Clin. Chim. Acta"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1007\/BF00198849","article-title":"Association of hepatitis C virus in human sera with beta-lipoprotein","volume":"181","author":"Thomssen","year":"1992","journal-title":"Med. Microbiol. Immunol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"6919","DOI":"10.1128\/JVI.76.14.6919-6928.2002","article-title":"Characterization of low- and very-low-density hepatitis C virus RNA-containing particles","volume":"76","author":"Deforges","year":"2002","journal-title":"J. Virol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"562","DOI":"10.1016\/j.chom.2014.10.009","article-title":"The impact of hepatitis C virus entry on viral tropism","volume":"16","author":"Ding","year":"2014","journal-title":"Cell Host Microbe"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1007\/978-981-10-4567-7_15","article-title":"Hepatitis C Virus Replication","volume":"997","author":"Suzuki","year":"2017","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1023\/B:DDAS.0000011597.92851.56","article-title":"Hepatic steatosis in hepatitis C virus genotype 3 infection: Does it correlate with body mass index, fibrosis, and HCV risk factors?","volume":"49","author":"Sharma","year":"2004","journal-title":"Dig. Dis. Sci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1097\/00042737-200603000-00002","article-title":"Prevalence of liver steatosis in patients with chronic hepatitis B: A study of associated factors and of relationship with fibrosis","volume":"18","author":"Thomopoulos","year":"2006","journal-title":"Eur. J. Gastroenterol. Hepatol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1111\/j.1478-3231.2008.01950.x","article-title":"Hepatitis C virus, steatosis and lipid abnormalities: Clinical and pathogenic data","volume":"29","author":"Negro","year":"2009","journal-title":"Liver Int."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1002\/hep.22288","article-title":"Morphological changes in intracellular lipid droplets induced by different hepatitis C virus genotype core sequences and relationship with steatosis","volume":"48","author":"Piodi","year":"2008","journal-title":"Hepatology"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"42615","DOI":"10.1074\/jbc.M111.285148","article-title":"Hepatitis C virus core protein decreases lipid droplet turnover: A mechanism for core-induced steatosis","volume":"286","author":"Harris","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1295","DOI":"10.1038\/nm.2238","article-title":"Efficient hepatitis C virus particle formation requires diacylglycerol acyltransferase-1","volume":"16","author":"Herker","year":"2010","journal-title":"Nat. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"8122","DOI":"10.1128\/JVI.00125-07","article-title":"Hepatitis C virus induces proteolytic cleavage of sterol regulatory element binding proteins and stimulates their phosphorylation via oxidative stress","volume":"81","author":"Waris","year":"2007","journal-title":"J. Virol."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Chang, M.L., Yeh, C.T., Chen, J.C., Huang, C.C., Lin, S.M., Sheen, I.S., Tai, D.I., Chu, C.M., Lin, W.P., and Chang, M.Y. (2008). Altered expression patterns of lipid metabolism genes in an animal model of HCV core-related, nonobese, modest hepatic steatosis. BMC Genom., 9.","DOI":"10.1186\/1471-2164-9-109"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"33466","DOI":"10.1074\/jbc.M109.019810","article-title":"Hepatitis C virus proteins induce lipogenesis and defective triglyceride secretion in transgenic mice","volume":"284","author":"Lerat","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"264017","DOI":"10.1155\/2012\/264017","article-title":"Metabolic disorders and steatosis in patients with chronic hepatitis C: Metabolic strategies for antiviral treatments","volume":"2012","author":"Enjoji","year":"2012","journal-title":"Int. J. Hepatol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"39802","DOI":"10.1074\/jbc.M510391200","article-title":"Hepatitis C virus nonstructural proteins inhibit apolipoprotein B100 secretion","volume":"280","author":"Domitrovich","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1661","DOI":"10.1053\/j.gastro.2006.02.035","article-title":"Liver microsomal triglyceride transfer protein is involved in hepatitis C liver steatosis","volume":"130","author":"Mirandola","year":"2006","journal-title":"Gastroenterology"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Cermelli, S., Ruggieri, A., Marrero, J.A., Ioannou, G.N., and Beretta, L. (2011). Circulating microRNAs in patients with chronic hepatitis C and non-alcoholic fatty liver disease. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0023937"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1111\/j.1872-034X.2011.00803.x","article-title":"Hepatitis C virus infection causes hypolipidemia regardless of hepatic damage or nutritional state: An epidemiological survey of a large Japanese cohort","volume":"41","author":"Miyazaki","year":"2011","journal-title":"Hepatol. Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"6348948","DOI":"10.1155\/2018\/6348948","article-title":"The Correlation between miR-122 and Lipoprotein Lipase Expression in Chronic Hepatitis C Patients","volume":"2018","author":"Sidorkiewicz","year":"2018","journal-title":"Can. J. Gastroenterol. Hepatol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1697","DOI":"10.1002\/hep.25990","article-title":"Elevated lipogenesis and diminished cholesterol synthesis in patients with hepatitis C viral infection compared to healthy humans","volume":"57","author":"Lambert","year":"2013","journal-title":"Hepatology"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1096\/fj.01-0396com","article-title":"Hepatitis C virus core protein inhibits microsomal triglyceride transfer protein activity and very low density lipoprotein secretion: A model of viral-related steatosis","volume":"16","author":"Perlemuter","year":"2002","journal-title":"FASEB J."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1016\/S0168-8278(00)00036-2","article-title":"Hepatitis C virus induced hypobetalipoproteinemia: A possible mechanism for steatosis in chronic hepatitis C","volume":"34","author":"Serfaty","year":"2001","journal-title":"J. Hepatol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1030","DOI":"10.1002\/hep.23219","article-title":"Hepatitis C virus infection and its clearance alter circulating lipids: Implications for long-term follow-up","volume":"50","author":"Corey","year":"2009","journal-title":"Hepatology"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"201","DOI":"10.5009\/gnl17179","article-title":"Rapid Changes in Serum Lipid Profiles during Combination Therapy with Daclatasvir and Asunaprevir in Patients Infected with Hepatitis C Virus Genotype 1b","volume":"12","author":"Chida","year":"2018","journal-title":"Gut Liver"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"e366","DOI":"10.1111\/j.1365-2893.2011.01434.x","article-title":"Acute hepatitis C infection lowers serum lipid levels","volume":"18","author":"Corey","year":"2011","journal-title":"J. Viral Hepat."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"8752","DOI":"10.1128\/JVI.02642-06","article-title":"Characterization of fusion determinants points to the involvement of three discrete regions of both E1 and E2 glycoproteins in the membrane fusion process of hepatitis C virus","volume":"81","author":"Lavillette","year":"2007","journal-title":"J. Virol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1002\/jmv.10208","article-title":"Hepatitis C virus particles of different density in the blood of chronically infected immunocompetent and immunodeficient patients: Implications for virus clearance by antibody","volume":"68","author":"Pumeechockchai","year":"2002","journal-title":"J. Med. Virol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2418","DOI":"10.1128\/JVI.80.5.2418-2428.2006","article-title":"Association between hepatitis C virus and very-low-density lipoprotein (VLDL)\/LDL analyzed in iodixanol density gradients","volume":"80","author":"Nielsen","year":"2006","journal-title":"J. Virol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2507","DOI":"10.1099\/vir.0.2008\/000083-0","article-title":"Characterization of hepatitis C RNA-containing particles from human liver by density and size","volume":"89","author":"Nielsen","year":"2008","journal-title":"J. Gen. Virol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1695","DOI":"10.1515\/cclm-2013-0358","article-title":"Recent advances in physiological lipoprotein metabolism","volume":"52","author":"Ramasamy","year":"2014","journal-title":"Clin. Chem. Lab. Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1586\/14789450.5.1.91","article-title":"Elucidation of lipoprotein particles structure by proteomic analysis","volume":"5","author":"Alonzi","year":"2008","journal-title":"Expert Rev. Proteom."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"680","DOI":"10.1136\/gut.2010.222133","article-title":"Insulin resistance and low-density apolipoprotein B-associated lipoviral particles in hepatitis C virus genotype 1 infection","volume":"60","author":"Bridge","year":"2011","journal-title":"Gut"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1186\/1743-7075-7-35","article-title":"Recent progress in understanding protein and lipid factors affecting hepatic VLDL assembly and secretion","volume":"7","author":"Sundaram","year":"2010","journal-title":"Nutr. Metab."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2178","DOI":"10.1172\/JCI111644","article-title":"Metabolism of apolipoprotein B in large triglyceride-rich very low density lipoproteins of normal and hypertriglyceridemic subjects","volume":"74","author":"Packard","year":"1984","journal-title":"J. Clin. Investig."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1002\/hep.25628","article-title":"High plasma level of nucleocapsid-free envelope glycoprotein-positive lipoproteins in hepatitis C patients","volume":"56","author":"Scholtes","year":"2012","journal-title":"Hepatology"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"10999","DOI":"10.1128\/JVI.00526-10","article-title":"Ultrastructural and biophysical characterization of hepatitis C virus particles produced in cell culture","volume":"84","author":"Gastaminza","year":"2010","journal-title":"J. Virol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"8240","DOI":"10.1128\/JVI.75.17.8240-8250.2001","article-title":"Nonenveloped nucleocapsids of hepatitis C virus in the serum of infected patients","volume":"75","author":"Maillard","year":"2001","journal-title":"J. Virol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"15975","DOI":"10.3748\/wjg.v20.i43.15975","article-title":"Impact of lipids and lipoproteins on hepatitis C virus infection and virus neutralization","volume":"20","author":"Vercauteren","year":"2014","journal-title":"World J. Gastroenterol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1487","DOI":"10.1136\/gutjnl-2016-311726","article-title":"Ultrastructural organisation of HCV from the bloodstream of infected patients revealed by electron microscopy after specific immunocapture","volume":"66","author":"Piver","year":"2017","journal-title":"Gut"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1355","DOI":"10.1053\/j.gastro.2010.06.058","article-title":"Production of infectious hepatitis C virus in primary cultures of human adult hepatocytes","volume":"139","author":"Podevin","year":"2010","journal-title":"Gastroenterology"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"11074","DOI":"10.1128\/JVI.01150-06","article-title":"Differential biophysical properties of infectious intracellular and secreted hepatitis C virus particles","volume":"80","author":"Gastaminza","year":"2006","journal-title":"J. Virol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"13783","DOI":"10.1128\/JVI.01091-07","article-title":"Human apolipoprotein e is required for infectivity and production of hepatitis C virus in cell culture","volume":"81","author":"Chang","year":"2007","journal-title":"J. Virol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2120","DOI":"10.1128\/JVI.02053-07","article-title":"Cellular determinants of hepatitis C virus assembly, maturation, degradation, and secretion","volume":"82","author":"Gastaminza","year":"2008","journal-title":"J. Virol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1038\/nm1268","article-title":"Production of infectious hepatitis C virus in tissue culture from a cloned viral genome","volume":"11","author":"Wakita","year":"2005","journal-title":"Nat. Med."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1194\/jlr.D008888","article-title":"Huh-7 or HepG2 cells: Which is the better model for studying human apolipoprotein-B100 assembly and secretion?","volume":"52","author":"Meex","year":"2011","journal-title":"J. Lipid Res."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"688","DOI":"10.1038\/nrmicro3098","article-title":"The ins and outs of hepatitis C virus entry and assembly","volume":"11","author":"Lindenbach","year":"2013","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1038\/nm.2341","article-title":"EGFR and EphA2 are host factors for hepatitis C virus entry and possible targets for antiviral therapy","volume":"17","author":"Lupberger","year":"2011","journal-title":"Nat. Med."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"6866","DOI":"10.1128\/JVI.03475-12","article-title":"Syndecan-1 serves as the major receptor for attachment of hepatitis C virus to the surfaces of hepatocytes","volume":"87","author":"Shi","year":"2013","journal-title":"J. Virol."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Lef\u00e8vre, M., Felmlee, D.J., Parnot, M., Baumert, T.F., and Schuster, C. (2014). Syndecan 4 is involved in mediating HCV entry through interaction with lipoviral particle-associated apolipoprotein E. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0095550"},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Jiang, J., Wu, X., Tang, H., and Luo, G. (2013). Apolipoprotein E mediates attachment of clinical hepatitis C virus to hepatocytes by binding to cell surface heparan sulfate proteoglycan receptors. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0067982"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"3846","DOI":"10.1128\/JVI.03647-14","article-title":"Characterization of hepatitis C virus interaction with heparan sulfate proteoglycans","volume":"89","author":"Xu","year":"2015","journal-title":"J. Virol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.virol.2009.08.037","article-title":"Apolipoprotein E on hepatitis C virion facilitates infection through interaction with low-density lipoprotein receptor","volume":"394","author":"Owen","year":"2009","journal-title":"Virology"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1149","DOI":"10.1002\/hep.24523","article-title":"Hepatitis C virus E1 envelope glycoprotein interacts with apolipoproteins in facilitating entry into hepatocytes","volume":"54","author":"Mazumdar","year":"2011","journal-title":"Hepatology"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"2174","DOI":"10.1194\/jlr.M037713","article-title":"The LXR-IDOL axis defines a clathrin-, caveolae-, and dynamin-independent endocytic route for LDLR internalization and lysosomal degradation","volume":"54","author":"Sorrentino","year":"2013","journal-title":"J. Lipid Res."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"998","DOI":"10.1002\/hep.25501","article-title":"Role of low-density lipoprotein receptor in the hepatitis C virus life cycle","volume":"55","author":"Albecka","year":"2012","journal-title":"Hepatology"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1016\/j.jhep.2006.09.024","article-title":"The low-density lipoprotein receptor plays a role in the infection of primary human hepatocytes by hepatitis C virus","volume":"46","author":"Molina","year":"2007","journal-title":"J. Hepatol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1002\/(SICI)1096-9071(199903)57:3<223::AID-JMV2>3.0.CO;2-4","article-title":"Low density lipoprotein receptor as a candidate receptor for hepatitis C virus","volume":"57","author":"Monazahian","year":"1999","journal-title":"J. Med. Virol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1282","DOI":"10.1111\/j.1365-2036.2009.04012.x","article-title":"Apolipoprotein B-associated cholesterol is a determinant of treatment outcome in patients with chronic hepatitis C virus infection receiving anti-viral agents interferon-alpha and ribavirin","volume":"29","author":"Sheridan","year":"2009","journal-title":"Aliment Pharmacol. Ther."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"5017","DOI":"10.1093\/emboj\/cdf529","article-title":"The human scavenger receptor class B type I is a novel candidate receptor for the hepatitis C virus","volume":"21","author":"Scarselli","year":"2002","journal-title":"EMBO J."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Dreux, M., Dao Thi, V.L., Fresquet, J., Gu\u00e9rin, M., Julia, Z., Verney, G., Durantel, D., Zoulim, F., Lavillette, D., and Cosset, F.L. (2009). Receptor complementation and mutagenesis reveal SR-BI as an essential HCV entry factor and functionally imply its intra- and extra-cellular domains. PLoS Pathog., 5.","DOI":"10.1371\/journal.ppat.1000310"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1002\/hep.26097","article-title":"The postbinding activity of scavenger receptor class B type I mediates initiation of hepatitis C virus infection and viral dissemination","volume":"57","author":"Zahid","year":"2013","journal-title":"Hepatology"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1096\/fj.05-4728fje","article-title":"The interaction of natural hepatitis C virus with human scavenger receptor SR-BI\/Cla1 is mediated by ApoB-containing lipoproteins","volume":"20","author":"Maillard","year":"2006","journal-title":"FASEB J."},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Gong, Y., and Cun, W. (2019). The Role of ApoE in HCV Infection and Comorbidity. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20082037"},{"key":"ref_73","first-page":"401","article-title":"Hepatitis C virus internalization","volume":"17","author":"Zona","year":"2013","journal-title":"Virologie"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1016\/j.chom.2013.02.006","article-title":"HRas signal transduction promotes hepatitis C virus cell entry by triggering assembly of the host tetraspanin receptor complex","volume":"13","author":"Zona","year":"2013","journal-title":"Cell Host Microbe"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1016\/j.chom.2018.02.005","article-title":"Single Particle Imaging of Polarized Hepatoma Organoids upon Hepatitis C Virus Infection Reveals an Ordered and Sequential Entry Process","volume":"23","author":"Baktash","year":"2018","journal-title":"Cell Host Microbe"},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Coller, K.E., Berger, K.L., Heaton, N.S., Cooper, J.D., Yoon, R., and Randall, G. (2009). RNA interference and single particle tracking analysis of hepatitis C virus endocytosis. PLoS Pathog., 5.","DOI":"10.1371\/journal.ppat.1000702"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"32357","DOI":"10.1074\/jbc.M705358200","article-title":"The exchangeable apolipoprotein ApoC-I promotes membrane fusion of hepatitis C virus","volume":"282","author":"Dreux","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Niepmann, M., and Gerresheim, G.K. (2020). Hepatitis C Virus Translation Regulation. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21072328"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.cmet.2006.01.005","article-title":"miR-122 regulation of lipid metabolism revealed by in vivo antisense targeting","volume":"3","author":"Esau","year":"2006","journal-title":"Cell Metab."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1577","DOI":"10.1126\/science.1113329","article-title":"Modulation of hepatitis C virus RNA abundance by a liver-specific MicroRNA","volume":"309","author":"Jopling","year":"2005","journal-title":"Science"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"7716","DOI":"10.1093\/nar\/gkr426","article-title":"miR-122 activates hepatitis C virus translation by a specialized mechanism requiring particular RNA components","volume":"39","author":"Roberts","year":"2011","journal-title":"Nucleic Acids Res."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"5307","DOI":"10.1093\/nar\/gkz194","article-title":"miR-122 and Ago interactions with the HCV genome alter the structure of the viral 5\u2032 terminus","volume":"47","author":"Chahal","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"2561","DOI":"10.1073\/pnas.0409834102","article-title":"Hepatitis C virus RNA replication is regulated by host geranylgeranylation and fatty acids","volume":"102","author":"Kapadia","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1016\/j.molcel.2005.04.004","article-title":"Identification of FBL2 as a geranylgeranylated cellular protein required for hepatitis C virus RNA replication","volume":"18","author":"Wang","year":"2005","journal-title":"Mol. Cell"},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Romero-Brey, I., Merz, A., Chiramel, A., Lee, J.Y., Chlanda, P., Haselman, U., Santarella-Mellwig, R., Habermann, A., Hoppe, S., and Kallis, S. (2012). Three-dimensional architecture and biogenesis of membrane structures associated with hepatitis C virus replication. PLoS Pathog., 8.","DOI":"10.1371\/journal.ppat.1003056"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1089","DOI":"10.1038\/ncb1631","article-title":"The lipid droplet is an important organelle for hepatitis C virus production","volume":"9","author":"Miyanari","year":"2007","journal-title":"Nat. Cell Biol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"5487","DOI":"10.1128\/JVI.77.9.5487-5492.2003","article-title":"Identification of the hepatitis C virus RNA replication complex in Huh-7 cells harboring subgenomic replicons","volume":"77","author":"Gosert","year":"2003","journal-title":"J. Virol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"5974","DOI":"10.1128\/JVI.76.12.5974-5984.2002","article-title":"Expression of hepatitis C virus proteins induces distinct membrane alterations including a candidate viral replication complex","volume":"76","author":"Egger","year":"2002","journal-title":"J. Virol."},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Mingorance, L., Castro, V., \u00c1vila-P\u00e9rez, G., Calvo, G., Rodriguez, M.J., Carrascosa, J.L., P\u00e9rez-Del-Pulgar, S., Forns, X., and Gastaminza, P. (2018). Host phosphatidic acid phosphatase lipin1 is rate limiting for functional hepatitis C virus replicase complex formation. PLoS Pathog., 14.","DOI":"10.1371\/journal.ppat.1007284"},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Stoeck, I.K., Lee, J.Y., Tabata, K., Romero-Brey, I., Paul, D., Schult, P., Lohmann, V., Kaderali, L., and Bartenschlager, R. (2018). Hepatitis C Virus Replication Depends on Endosomal Cholesterol Homeostasis. J. Virol., 92.","DOI":"10.1128\/JVI.01196-17"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.chom.2010.12.002","article-title":"Recruitment and activation of a lipid kinase by hepatitis C virus NS5A is essential for integrity of the membranous replication compartment","volume":"9","author":"Reiss","year":"2011","journal-title":"Cell Host Microbe"},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Bianco, A., Reghellin, V., Donnici, L., Fenu, S., Alvarez, R., Baruffa, C., Peri, F., Pagani, M., Abrignani, S., and Neddermann, P. (2012). Metabolism of phosphatidylinositol 4-kinase III\u03b1-dependent PI4P Is subverted by HCV and is targeted by a 4-anilino quinazoline with antiviral activity. PLoS Pathog., 8.","DOI":"10.1371\/journal.ppat.1002576"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"4160","DOI":"10.1128\/JVI.77.7.4160-4168.2003","article-title":"Hepatitis C virus RNA replication occurs on a detergent-resistant membrane that cofractionates with caveolin-2","volume":"77","author":"Shi","year":"2003","journal-title":"J. Virol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1053\/j.gastro.2014.11.043","article-title":"Phosphatidylinositol 4,5-bisphosphate is an HCV NS5A ligand and mediates replication of the viral genome","volume":"148","author":"Cho","year":"2015","journal-title":"Gastroenterology"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"12276","DOI":"10.1128\/JVI.00970-14","article-title":"Modulation of hepatitis C virus genome replication by glycosphingolipids and four-phosphate adaptor protein 2","volume":"88","author":"Khan","year":"2014","journal-title":"J. Virol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1373","DOI":"10.1053\/j.gastro.2014.02.002","article-title":"Oxysterol-binding protein is a phosphatidylinositol 4-kinase effector required for HCV replication membrane integrity and cholesterol trafficking","volume":"146","author":"Wang","year":"2014","journal-title":"Gastroenterology"},{"key":"ref_97","doi-asserted-by":"crossref","unstructured":"Wang, H., and Tai, A.W. (2019). Nir2 Is an Effector of VAPs Necessary for Efficient Hepatitis C Virus Replication and Phosphatidylinositol 4-Phosphate Enrichment at the Viral Replication Organelle. J. Virol., 93.","DOI":"10.1128\/JVI.00742-19"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"16247","DOI":"10.1038\/nmicrobiol.2016.247","article-title":"Tuning a cellular lipid kinase activity adapts hepatitis C virus to replication in cell culture","volume":"2","author":"Harak","year":"2016","journal-title":"Nat. Microbiol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1041","DOI":"10.1016\/j.bbalip.2018.06.002","article-title":"Complex lipid metabolic remodeling is required for efficient hepatitis C virus replication","volume":"1863","author":"Hofmann","year":"2018","journal-title":"Biochim. Biophys. Acta Mol. Cell Biol. Lipids"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1016\/j.bbrc.2004.04.019","article-title":"Anti-HCV activities of selective polyunsaturated fatty acids","volume":"318","author":"Leu","year":"2004","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"3602","DOI":"10.1016\/j.celrep.2019.05.063","article-title":"Spatiotemporal Coupling of the Hepatitis C Virus Replication Cycle by Creating a Lipid Droplet- Proximal Membranous Replication Compartment","volume":"27","author":"Lee","year":"2019","journal-title":"Cell Rep."},{"key":"ref_102","first-page":"199","article-title":"Virion assembly and release","volume":"369","author":"Lindenbach","year":"2013","journal-title":"Curr. Top. Microbiol. Immunol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"21506","DOI":"10.1074\/jbc.M412989200","article-title":"Increased very low density lipoprotein secretion and gonadal fat mass in mice overexpressing liver DGAT1","volume":"280","author":"Yamazaki","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"1200","DOI":"10.1073\/pnas.94.4.1200","article-title":"Hepatitis C virus core protein shows a cytoplasmic localization and associates to cellular lipid storage droplets","volume":"94","author":"Barba","year":"1997","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"6814","DOI":"10.1128\/JVI.79.11.6814-6826.2005","article-title":"Identification of residues in the hepatitis C virus core protein that are critical for capsid assembly in a cell-free system","volume":"79","author":"Klein","year":"2005","journal-title":"J. Virol."},{"key":"ref_106","doi-asserted-by":"crossref","unstructured":"Shi, G., Ando, T., Suzuki, R., Matsuda, M., Nakashima, K., Ito, M., Omatsu, T., Oba, M., Ochiai, H., and Kato, T. (2016). Involvement of the 3\u2032 Untranslated Region in Encapsidation of the Hepatitis C Virus. PLoS Pathog., 12.","DOI":"10.1371\/journal.ppat.1005441"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"7964","DOI":"10.1128\/JVI.00826-08","article-title":"Interaction of hepatitis C virus nonstructural protein 5A with core protein is critical for the production of infectious virus particles","volume":"82","author":"Masaki","year":"2008","journal-title":"J. Virol."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.tim.2010.11.005","article-title":"Assembly of infectious hepatitis C virus particles","volume":"19","author":"Bartenschlager","year":"2011","journal-title":"Trends Microbiol."},{"key":"ref_109","doi-asserted-by":"crossref","unstructured":"Icard, V., Diaz, O., Scholtes, C., Perrin-Cocon, L., Rami\u00e8re, C., Bartenschlager, R., Penin, F., Lotteau, V., and Andr\u00e9, P. (2009). Secretion of hepatitis C virus envelope glycoproteins depends on assembly of apolipoprotein B positive lipoproteins. PLoS ONE, 4.","DOI":"10.1371\/journal.pone.0004233"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"12422","DOI":"10.1128\/JVI.01660-14","article-title":"Apolipoprotein E likely contributes to a maturation step of infectious hepatitis C virus particles and interacts with viral envelope glycoproteins","volume":"88","author":"Lee","year":"2014","journal-title":"J. Virol."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"1433","DOI":"10.1128\/JVI.01815-13","article-title":"Apolipoprotein E codetermines tissue tropism of hepatitis C virus and is crucial for viral cell-to-cell transmission by contributing to a postenvelopment step of assembly","volume":"88","author":"Hueging","year":"2014","journal-title":"J. Virol."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"18904","DOI":"10.1074\/jbc.M113.538256","article-title":"The association of hepatitis C virus glycoproteins with apolipoproteins E and B early in assembly is conserved in lipoviral particles","volume":"289","author":"Boyer","year":"2014","journal-title":"J. Biol. Chem."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"9962","DOI":"10.1128\/JVI.00577-15","article-title":"Apolipoprotein E, but Not Apolipoprotein B, Is Essential for Efficient Cell-to-Cell Transmission of Hepatitis C Virus","volume":"89","author":"Gondar","year":"2015","journal-title":"J. Virol."},{"key":"ref_114","doi-asserted-by":"crossref","unstructured":"Fukuhara, T., Wada, M., Nakamura, S., Ono, C., Shiokawa, M., Yamamoto, S., Motomura, T., Okamoto, T., Okuzaki, D., and Yamamoto, M. (2014). Amphipathic \u03b1-helices in apolipoproteins are crucial to the formation of infectious hepatitis C virus particles. PLoS Pathog., 10.","DOI":"10.1371\/journal.ppat.1004534"},{"key":"ref_115","doi-asserted-by":"crossref","unstructured":"Fukuhara, T., Tamura, T., Ono, C., Shiokawa, M., Mori, H., Uemura, K., Yamamoto, S., Kurihara, T., Okamoto, T., and Suzuki, R. (2017). Host-derived apolipoproteins play comparable roles with viral secretory proteins Erns and NS1 in the infectious particle formation of Flaviviridae. PLoS Pathog., 13.","DOI":"10.1371\/journal.ppat.1006475"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1126\/science.282.5386.103","article-title":"Hepatitis C viral dynamics in vivo and the antiviral efficacy of interferon-alpha therapy","volume":"282","author":"Neumann","year":"1998","journal-title":"Science"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1161\/ATVBAHA.111.241471","article-title":"Intracellular trafficking and secretion of VLDL","volume":"32","author":"Tiwari","year":"2012","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_118","doi-asserted-by":"crossref","unstructured":"Cosset, F.L., Mialon, C., Boson, B., Granier, C., and Denolly, S. (2020). HCV Interplay with Lipoproteins: Inside or Outside the Cells?. Viruses, 12.","DOI":"10.3390\/v12040434"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"5848","DOI":"10.1073\/pnas.0700760104","article-title":"Hepatitis C virus production by human hepatocytes dependent on assembly and secretion of very low-density lipoproteins","volume":"104","author":"Huang","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"2983","DOI":"10.1099\/vir.0.82033-0","article-title":"Preferential association of Hepatitis C virus with apolipoprotein B48-containing lipoproteins","volume":"87","author":"Diaz","year":"2006","journal-title":"J. Gen. Virol."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1016\/j.jhep.2018.11.033","article-title":"A serum protein factor mediates maturation and apoB-association of HCV particles in the extracellular milieu","volume":"70","author":"Denolly","year":"2019","journal-title":"J. Hepatol."}],"container-title":["Metabolites"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-1989\/11\/5\/273\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:53:12Z","timestamp":1760161992000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-1989\/11\/5\/273"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,4,27]]},"references-count":121,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2021,5]]}},"alternative-id":["metabo11050273"],"URL":"https:\/\/doi.org\/10.3390\/metabo11050273","relation":{},"ISSN":["2218-1989"],"issn-type":[{"value":"2218-1989","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,4,27]]}}}