{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T14:43:01Z","timestamp":1791297781181,"version":"4.1.0"},"reference-count":107,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2014,2,18]],"date-time":"2014-02-18T00:00:00Z","timestamp":1392681600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Tetraspanins are integral transmembrane proteins organized in microdomains displaying specific and direct interactions with other tetraspanins and molecular partners. Among them, CD81 has been implicated in a variety of physiological and pathological processes. CD81 also plays a crucial role in pathogen entry into host cells, including hepatitis C virus (HCV) entry into hepatocytes. HCV is a major cause of liver cirrhosis and hepatocellular carcinoma. HCV entry into hepatocytes is a complex process that requires the coordinated interaction of viral and host factors for the initiation of infection, including CD81, scavenger receptor BI, claudin-1, occludin, membrane-bound host cell kinases, Niemann-Pick C1 Like 1, Harvey rat sarcoma viral oncogene homolog (HRas), CD63 and transferrin receptor 1. Furthermore, recent data in HCV model systems have demonstrated that targeting critical components of tetraspanins and associated cell membrane proteins open new avenues to prevent and treat viral infection.<\/jats:p>","DOI":"10.3390\/v6020875","type":"journal-article","created":{"date-parts":[[2014,2,18]],"date-time":"2014-02-18T11:07:10Z","timestamp":1392721630000},"page":"875-892","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":44,"title":["CD81-Receptor Associations \u2014 Impact for Hepatitis C Virus Entry and Antiviral Therapies"],"prefix":"10.3390","volume":"6","author":[{"given":"Laetitia","family":"Zona","sequence":"first","affiliation":[{"name":"Inserm, U1110, 67000 Strasbourg, France"},{"name":"University of Strasbourg, 67000 Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajiv","family":"Tawar","sequence":"additional","affiliation":[{"name":"Inserm, U1110, 67000 Strasbourg, France"},{"name":"University of Strasbourg, 67000 Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mirjam","family":"Zeisel","sequence":"additional","affiliation":[{"name":"Inserm, U1110, 67000 Strasbourg, France"},{"name":"University of Strasbourg, 67000 Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fei","family":"Xiao","sequence":"additional","affiliation":[{"name":"Inserm, U1110, 67000 Strasbourg, France"},{"name":"University of Strasbourg, 67000 Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Schuster","sequence":"additional","affiliation":[{"name":"Inserm, U1110, 67000 Strasbourg, France"},{"name":"University of Strasbourg, 67000 Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joachim","family":"Lupberger","sequence":"additional","affiliation":[{"name":"Inserm, U1110, 67000 Strasbourg, France"},{"name":"University of Strasbourg, 67000 Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Baumert","sequence":"additional","affiliation":[{"name":"Inserm, U1110, 67000 Strasbourg, France"},{"name":"University of Strasbourg, 67000 Strasbourg, France"},{"name":"P\u00f4le H\u00e9pato-digestif, H\u00f4pitaux Universitaires de Strasbourg, 67000 Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2014,2,18]]},"reference":[{"key":"ref_1","first-page":"4007","article-title":"TAPA-1, the target of an antiproliferative antibody, defines a new family of transmembrane proteins","volume":"10","author":"Oren","year":"1990","journal-title":"Mol. Cell. Biol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1038\/nri1548","article-title":"The tetraspanin web modulates immune-signalling complexes","volume":"5","author":"Levy","year":"2005","journal-title":"Nat. Rev. Immunol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1189","DOI":"10.1007\/PL00000933","article-title":"Tetraspanins","volume":"58","author":"Boucheix","year":"2001","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/S0014-5793(02)02522-X","article-title":"Differential stability of tetraspanin\/tetraspanin interactions: Role of palmitoylation","volume":"516","author":"Charrin","year":"2002","journal-title":"FEBS Lett."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2479","DOI":"10.1002\/eji.200323884","article-title":"A physical and functional link between cholesterol and tetraspanins","volume":"33","author":"Charrin","year":"2003","journal-title":"Eur. J. Immunol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"36991","DOI":"10.1074\/jbc.M205265200","article-title":"Expression of the palmitoylation-deficient CD151 weakens the association of alpha 3 beta 1 integrin with the tetraspanin-enriched microdomains and affects integrin-dependent signaling","volume":"277","author":"Berditchevski","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1091\/mbc.01-05-0275","article-title":"Palmitoylation of tetraspanin proteins: Modulation of CD151 lateral interactions, subcellular distribution, and integrin-dependent cell morphology","volume":"13","author":"Yang","year":"2002","journal-title":"Mol. Biol. Cell"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"7974","DOI":"10.1074\/jbc.M008650200","article-title":"Evaluation of prototype transmembrane 4 superfamily protein complexes and their relation to lipid rafts","volume":"276","author":"Claas","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1038\/nrm1736","article-title":"Tetraspanin functions and associated microdomains","volume":"6","author":"Hemler","year":"2005","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"6447","DOI":"10.1002\/pmic.200600282","article-title":"Membrane microdomains and proteomics: Lessons from tetraspanin microdomains and comparison with lipid rafts","volume":"6","author":"Andre","year":"2006","journal-title":"Proteomics"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1146\/annurev.cellbio.19.111301.153609","article-title":"Tetraspanin proteins mediate cellular penetration, invasion, and fusion events and define a novel type of membrane microdomain","volume":"19","author":"Hemler","year":"2003","journal-title":"Annu. Rev. Cell Dev. Biol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"10839","DOI":"10.1128\/JVI.79.17.10839-10851.2005","article-title":"Tetraspanins in viral infections: A fundamental role in viral biology?","volume":"79","author":"Martin","year":"2005","journal-title":"J. Virol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1042\/BJ20091000","article-title":"The hepatitis C virus and its hepatic environment: A toxic but finely tuned partnership","volume":"423","author":"Perrault","year":"2009","journal-title":"Biochem. J."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1042\/bj20031037","article-title":"Evidence for specific tetraspanin homodimers: Inhibition of palmitoylation makes cysteine residues available for cross-linking","volume":"377","author":"Kovalenko","year":"2004","journal-title":"Biochem. J."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1042\/bj3400103","article-title":"Selective tetraspan-integrin complexes (CD81\/alpha4beta1, CD151\/alpha3beta1, CD151\/alpha6beta1) under conditions disrupting tetraspan interactions","volume":"340","author":"Serru","year":"1999","journal-title":"Biochem. J."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1042\/bj20030343","article-title":"EWI-2 is a new component of the tetraspanin web in hepatocytes and lymphoid cells","volume":"373","author":"Charrin","year":"2003","journal-title":"Biochem. J."},{"key":"ref_17","first-page":"2665","article-title":"EWI2\/PGRL associates with the metastasis suppressor KAI1\/CD82 and inhibits the migration of prostate cancer cells","volume":"63","author":"Zhang","year":"2003","journal-title":"Canc. Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"19665","DOI":"10.1074\/jbc.M602116200","article-title":"EWI-2 and EWI-F link the tetraspanin web to the actin cytoskeleton through their direct association with ezrin-radixin-moesin proteins","volume":"281","author":"Ursa","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"4143","DOI":"10.1242\/jcs.114.23.4143","article-title":"Complexes of tetraspanins with integrins: More than meets the eye","volume":"114","author":"Berditchevski","year":"2001","journal-title":"J. Cell Sci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"4217","DOI":"10.1093\/emboj\/16.14.4217","article-title":"Normal development but differentially altered proliferative responses of lymphocytes in mice lacking CD81","volume":"16","author":"Miyazaki","year":"1997","journal-title":"EMBO J."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"10844","DOI":"10.1073\/pnas.94.20.10844","article-title":"Impaired CD19 expression and signaling, enhanced antibody response to type II T independent antigen and reduction of B-1 cells in CD81-deficient mice","volume":"94","author":"Tsitsikov","year":"1997","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1505","DOI":"10.1084\/jem.185.8.1505","article-title":"Normal lymphocyte development but delayed humoral immune response in CD81-null mice","volume":"185","author":"Maecker","year":"1997","journal-title":"J. Exp. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1265","DOI":"10.1172\/JCI39748","article-title":"CD81 gene defect in humans disrupts CD19 complex formation and leads to antibody deficiency","volume":"120","author":"Smet","year":"2010","journal-title":"J. Clin. Invest."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1566","DOI":"10.1038\/sj.onc.1207287","article-title":"Tetraspanin CD81 is linked to ERK\/MAPKinase signaling by Shc in liver tumor cells","volume":"23","author":"Carloni","year":"2004","journal-title":"Oncogene"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"25005","DOI":"10.1074\/jbc.M102156200","article-title":"Transmembrane-4 superfamily proteins associate with activated protein kinase C (PKC) and link PKC to specific beta(1) integrins","volume":"276","author":"Zhang","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1038\/nm808","article-title":"Hepatocyte CD81 is required for Plasmodium falciparum and Plasmodium yoelii sporozoite infectivity","volume":"9","author":"Silvie","year":"2003","journal-title":"Nat. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"e1000010","DOI":"10.1371\/journal.ppat.1000010","article-title":"Hepatocyte permissiveness to Plasmodium infection is conveyed by a short and structurally conserved region of the CD81 large extracellular domain","volume":"4","author":"Yalaoui","year":"2008","journal-title":"PLoS Pathog."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1128\/IAI.00661-09","article-title":"Tetraspanin CD81 is required for Listeria monocytogenes invasion","volume":"78","author":"Tham","year":"2010","journal-title":"Infect. Immun."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"938","DOI":"10.1126\/science.282.5390.938","article-title":"Binding of hepatitis C virus to CD81","volume":"282","author":"Pileri","year":"1998","journal-title":"Science"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"7270","DOI":"10.1073\/pnas.0402253101","article-title":"CD81 is an entry coreceptor for hepatitis C virus","volume":"101","author":"Cormier","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1448","DOI":"10.1128\/JVI.78.3.1448-1455.2004","article-title":"CD81 is required for hepatitis C virus glycoprotein-mediated viral infection","volume":"78","author":"Zhang","year":"2004","journal-title":"J. Virol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"5129","DOI":"10.4049\/jimmunol.177.8.5129","article-title":"Tetraspanins CD9 and CD81 modulate HIV-1-induced membrane fusion","volume":"177","author":"Barreiro","year":"2006","journal-title":"J. Immunol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2436","DOI":"10.3748\/wjg.v13.i17.2436","article-title":"Epidemiology of hepatitis C virus infection","volume":"13","author":"Alter","year":"2007","journal-title":"World J. Gastroenterol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1264","DOI":"10.1053\/j.gastro.2011.12.061","article-title":"Epidemiology of viral hepatitis and hepatocellular carcinoma","volume":"142","year":"2012","journal-title":"Gastroenterology"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1038\/nrc3449","article-title":"Pathogenic mechanisms in HBV- and HCV-associated hepatocellular carcinoma","volume":"13","author":"Arzumanyan","year":"2013","journal-title":"Nat. Rev. Canc."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1016\/j.cell.2006.02.007","article-title":"Virus entry: Open sesame","volume":"124","author":"Marsh","year":"2006","journal-title":"Cell"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1002\/hep.21959","article-title":"Hepatitis C virus cell-cell transmission in hepatoma cells in the presence of neutralizing antibodies","volume":"47","author":"Timpe","year":"2008","journal-title":"Hepatology"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"596","DOI":"10.1128\/JVI.01592-10","article-title":"Neutralizing antibody-resistant hepatitis C virus cell-to-cell transmission","volume":"85","author":"Brimacombe","year":"2011","journal-title":"J. Virol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"12407","DOI":"10.1128\/JVI.01552-09","article-title":"Hepatoma cell density promotes claudin-1 and scavenger receptor BI expression and hepatitis C virus internalization","volume":"83","author":"Schwarz","year":"2009","journal-title":"J. Virol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1053\/j.gastro.2012.04.006","article-title":"Mutations that alter use of hepatitis C virus cell entry factors mediate escape from neutralizing antibodies","volume":"143","author":"Fofana","year":"2012","journal-title":"Gastroenterology"},{"key":"ref_41","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_42","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_43","doi-asserted-by":"crossref","first-page":"7271","DOI":"10.1073\/pnas.0832180100","article-title":"Hepatitis C virus glycoproteins mediate pH-dependent cell entry of pseudotyped retroviral particles","volume":"100","author":"Hsu","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"e103","DOI":"10.1371\/journal.ppat.0030103","article-title":"Hepatitis C virus p7 protein is crucial for assembly and release of infectious virions","volume":"3","author":"Steinmann","year":"2007","journal-title":"PLoS Pathog."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"28546","DOI":"10.1074\/jbc.M803981200","article-title":"Structural and functional characterization of nonstructural protein 2 for its role in hepatitis C virus assembly","volume":"283","author":"Jirasko","year":"2008","journal-title":"J. Biol. Chem."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2163","DOI":"10.1128\/JVI.01885-08","article-title":"The hepatitis C virus NS4B protein can trans-complement viral RNA replication and modulates production of infectious virus","volume":"83","author":"Jones","year":"2009","journal-title":"J. Virol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"7624","DOI":"10.1128\/JVI.00724-08","article-title":"NS3 helicase domains involved in infectious intracellular hepatitis C virus particle assembly","volume":"82","author":"Ma","year":"2008","journal-title":"J. Virol."},{"key":"ref_48","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_49","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_50","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1002\/hep.23278","article-title":"Apolipoprotein E interacts with hepatitis C virus nonstructural protein 5A and determines assembly of infectious particles","volume":"51","author":"Benga","year":"2010","journal-title":"Hepatology"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1084\/jem.20021756","article-title":"Infectious hepatitis C virus pseudo-particles containing functional E1-E2 envelope protein complexes","volume":"197","author":"Bartosch","year":"2003","journal-title":"J. Exp. Med."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"41624","DOI":"10.1074\/jbc.M305289200","article-title":"Cell entry of hepatitis C virus requires a set of co-receptors that include the CD81 tetraspanin and the SR-B1 scavenger receptor","volume":"278","author":"Bartosch","year":"2003","journal-title":"J. Biol. Chem."},{"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":"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_55","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1002\/hep.20542","article-title":"Characterization of host-range and cell entry properties of the major genotypes and subtypes of hepatitis C virus","volume":"41","author":"Lavillette","year":"2005","journal-title":"Hepatology"},{"key":"ref_56","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_57","doi-asserted-by":"crossref","first-page":"8496","DOI":"10.1128\/JVI.78.16.8496-8505.2004","article-title":"Diverse hepatitis C virus glycoproteins mediate viral infection in a CD81-dependent manner","volume":"78","author":"McKeating","year":"2004","journal-title":"J. Virol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"6211","DOI":"10.1128\/JVI.00246-09","article-title":"Polarization restricts hepatitis C virus entry into HepG2 hepatoma cells","volume":"83","author":"Mee","year":"2009","journal-title":"J. Virol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1128\/JVI.01534-06","article-title":"The level of CD81 cell surface expression is a key determinant for productive entry of hepatitis C virus into host cells","volume":"81","author":"Koutsoudakis","year":"2007","journal-title":"J. Virol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"5036","DOI":"10.1128\/JVI.01573-06","article-title":"CD81 expression is important for the permissiveness of Huh7 cell clones for heterogeneous hepatitis C virus infection","volume":"81","author":"Akazawa","year":"2007","journal-title":"J. Virol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"3396","DOI":"10.1128\/JVI.02391-09","article-title":"Novel function of CD81 in controlling hepatitis C virus replication","volume":"84","author":"Zhang","year":"2010","journal-title":"J. Virol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"6235","DOI":"10.1128\/JVI.73.8.6235-6244.1999","article-title":"Characterization of hepatitis C virus E2 glycoprotein interaction with a putative cellular receptor, CD81","volume":"73","author":"Flint","year":"1999","journal-title":"J. Virol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"4824","DOI":"10.1128\/jvi.74.10.4824-4830.2000","article-title":"Structure-function analysis of hepatitis C virus envelope-CD81 binding","volume":"74","author":"Petracca","year":"2000","journal-title":"J. Virol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"11143","DOI":"10.1128\/JVI.76.21.11143-11147.2002","article-title":"Identification of the hepatitis C virus E2 glycoprotein binding site on the large extracellular loop of CD81","volume":"76","author":"Drummer","year":"2002","journal-title":"J. Virol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0168-1702(01)00245-3","article-title":"The small extracellular loop of CD81 is necessary for optimal surface expression of the large loop, a putative HCV receptor","volume":"80","author":"Masciopinto","year":"2001","journal-title":"Virus Res."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"4940","DOI":"10.1128\/JVI.80.10.4940-4948.2006","article-title":"Different domains of CD81 mediate distinct stages of hepatitis C virus pseudoparticle entry","volume":"80","author":"Bertaux","year":"2006","journal-title":"J. Virol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1111\/j.1462-5822.2007.01070.x","article-title":"Ceramide enrichment of the plasma membrane induces CD81 internalization and inhibits hepatitis C virus entry","volume":"10","author":"Voisset","year":"2008","journal-title":"Cell. Microbiol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1128\/JVI.01134-06","article-title":"Initiation of hepatitis C virus infection is dependent on cholesterol and cooperativity between CD81 and scavenger receptor B type I","volume":"81","author":"Kapadia","year":"2007","journal-title":"J. Virol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1111\/cmi.12047","article-title":"Hepatoma polarization limits CD81 and hepatitis C virus dynamics","volume":"15","author":"Harris","year":"2013","journal-title":"Cell. Microbiol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"4305","DOI":"10.1128\/JVI.06996-11","article-title":"Hepatitis C virus induces CD81 and claudin-1 endocytosis","volume":"86","author":"Farquhar","year":"2012","journal-title":"J. Virol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"11331","DOI":"10.1128\/JVI.00104-06","article-title":"Diverse CD81 proteins support hepatitis C virus infection","volume":"80","author":"Flint","year":"2006","journal-title":"J. Virol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"3642","DOI":"10.1128\/JVI.74.8.3642-3649.2000","article-title":"Identification of amino acid residues in CD81 critical for interaction with hepatitis C virus envelope glycoprotein E2","volume":"74","author":"Higginbottom","year":"2000","journal-title":"J. Virol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1892","DOI":"10.1111\/cmi.12008","article-title":"In silico directed mutagenesis identifies the CD81\/claudin-1 hepatitis C virus receptor interface","volume":"14","author":"Davis","year":"2012","journal-title":"Cell. Microbiol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"13954","DOI":"10.1074\/jbc.M111.220103","article-title":"Interacting regions of CD81 and two of its partners, EWI-2 and EWI-2wint, and their effect on hepatitis C virus infection","volume":"286","author":"Montpellier","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"8316","DOI":"10.1128\/JVI.00665-08","article-title":"CD81 is a central regulator of cellular events required for hepatitis C virus infection of human hepatocytes","volume":"82","author":"Brazzoli","year":"2008","journal-title":"J. Virol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"11329","DOI":"10.1074\/jbc.M410161200","article-title":"Binding of hepatitis C virus envelope protein E2 to CD81 up-regulates matrix metalloproteinase-2 in human hepatic stellate cells","volume":"280","author":"Mazzocca","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_77","first-page":"87","article-title":"Hepatitis C virus entry","volume":"369","author":"Zeisel","year":"2013","journal-title":"Curr. Top. Microbiol. Immunol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"e60333","DOI":"10.1371\/journal.pone.0060333","article-title":"Discovery of cellular proteins required for the early steps of HCV infection using integrative genomics","volume":"8","author":"Park","year":"2013","journal-title":"PLoS One"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1152\/physiol.00015.2005","article-title":"Protein-protein interactions in the tetraspanin web","volume":"20","author":"Levy","year":"2005","journal-title":"Physiology"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"21092","DOI":"10.1074\/jbc.M110.104836","article-title":"Claudin association with CD81 defines hepatitis C virus entry","volume":"285","author":"Harris","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"5007","DOI":"10.1128\/JVI.02286-07","article-title":"CD81 and claudin 1 coreceptor association: Role in hepatitis C virus entry","volume":"82","author":"Harris","year":"2008","journal-title":"J. Virol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.1083\/jcb.200110122","article-title":"Claudin-based tight junctions are crucial for the mammalian epidermal barrier: A lesson from claudin-1-deficient mice","volume":"156","author":"Furuse","year":"2002","journal-title":"J. Cell Biol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1038\/nature05654","article-title":"Claudin-1 is a hepatitis C virus co-receptor required for a late step in entry","volume":"446","author":"Evans","year":"2007","journal-title":"Nature"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1144","DOI":"10.1002\/hep.23445","article-title":"Inhibition of hepatitis C virus infection by anti-claudin-1 antibodies is mediated by neutralization of E2-CD81-claudin-1 associations","volume":"51","author":"Krieger","year":"2010","journal-title":"Hepatology"},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Douam, F., Dao Thi, V.L., Maurin, G., Fresquet, J., Mompelat, D., Zeisel, M.B., Baumert, T.F., Cosset, F.L., and Lavillette, D. (2013). A critical interaction between E1 and E2 glycoproteins determines binding and fusion properties of hepatitis C virus during cell entry. Hepatology.","DOI":"10.1002\/hep.26733"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1002\/hep.22028","article-title":"Hepatitis C virus receptor expression in normal and diseased liver tissue","volume":"47","author":"Reynolds","year":"2008","journal-title":"Hepatology"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"8643","DOI":"10.1074\/jbc.M709824200","article-title":"Correlation of the tight junction-like distribution of Claudin-1 to the cellular tropism of hepatitis C virus","volume":"283","author":"Yang","year":"2008","journal-title":"J. Biol. Chem."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"8797","DOI":"10.1128\/JVI.00592-08","article-title":"Protein kinase A-dependent step(s) in hepatitis C virus entry and infectivity","volume":"82","author":"Farquhar","year":"2008","journal-title":"J. Virol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"41922","DOI":"10.1074\/jbc.M112.414789","article-title":"Transient Activation of the PI3K-AKT Pathway by Hepatitis C Virus to Enhance Viral Entry","volume":"287","author":"Liu","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"10935","DOI":"10.1128\/JVI.00750-12","article-title":"Hepatitis C virus induces epidermal growth factor receptor activation via CD81 binding for viral internalization and entry","volume":"86","author":"Diao","year":"2012","journal-title":"J. Virol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"818","DOI":"10.1038\/nature08760","article-title":"Genome-wide RNAi screen identifies human host factors crucial for influenza virus replication","volume":"463","author":"Karlas","year":"2010","journal-title":"Nature"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1016\/j.jhep.2012.09.022","article-title":"Host-targeting agents for prevention and treatment of chronic hepatitis C - perspectives and challenges","volume":"58","author":"Zeisel","year":"2013","journal-title":"J. Hepatol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"e64221","DOI":"10.1371\/journal.pone.0064221","article-title":"A novel monoclonal anti-CD81 antibody produced by genetic immunization efficiently inhibits Hepatitis C virus cell-cell transmission","volume":"8","author":"Fofana","year":"2013","journal-title":"PLoS One"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"714","DOI":"10.1002\/jmv.20842","article-title":"The roles of CD81 and glycosaminoglycans in the adsorption and uptake of infectious HCV particles","volume":"79","author":"Morikawa","year":"2007","journal-title":"J. Med. Virol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1761","DOI":"10.1002\/hep.22547","article-title":"Anti-CD81 antibodies can prevent a hepatitis C virus infection in vivo","volume":"48","author":"Meuleman","year":"2008","journal-title":"Hepatology"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1016\/S0042-6822(03)00406-9","article-title":"Small molecule inhibition of hepatitis C virus E2 binding to CD81","volume":"314","author":"Wiznycia","year":"2003","journal-title":"Virology"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"953","DOI":"10.1053\/j.gastro.2010.05.073","article-title":"Monoclonal anti-claudin 1 antibodies prevent hepatitis C virus infection of primary human hepatocytes","volume":"139","author":"Fofana","year":"2010","journal-title":"Gastroenterology"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1002\/hep.25685","article-title":"A human claudin-1-derived peptide inhibits hepatitis C virus entry","volume":"56","author":"Si","year":"2012","journal-title":"Hepatology"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1093\/protein\/gzr039","article-title":"Efficient production of antibodies against a mammalian integral membrane protein by phage display","volume":"24","author":"Hotzel","year":"2011","journal-title":"Protein Eng. Des. Sel."},{"key":"ref_100","unstructured":"Pilot-Matias, T., Lacy, S., Ng, T., Barbon, J., Fung, E., Pithawalla, R., Barlow, E., Kutskova, Y., Hsieh, C.-M., and DiGiammarino, E. (2010, January 10\u201314). Evaluation of a panel of anti-CD81 antibodies using human liver-uPA\/SCID mice. Proceedings of the 17th International Meeting on Hepatitis C Virus and Related Viruses, Yokohama, Japan."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1136\/gut.2010.212068","article-title":"Kinase inhibitors in the treatment of chronic hepatitis C virus","volume":"60","author":"Lorho","year":"2011","journal-title":"Gut"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"1225","DOI":"10.1002\/hep.26404","article-title":"EGFR signaling impairs the antiviral activity of interferon-alpha","volume":"58","author":"Lupberger","year":"2013","journal-title":"Hepatology"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/S0955-0674(99)00071-X","article-title":"The Ras branch of small GTPases: Ras family members don't fall far from the tree","volume":"12","author":"Reuther","year":"2000","journal-title":"Curr. Opin. Cell Biol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"1934","DOI":"10.1126\/science.8316833","article-title":"Selective inhibition of ras-dependent transformation by a farnesyltransferase inhibitor","volume":"260","author":"Kohl","year":"1993","journal-title":"Science"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"1937","DOI":"10.1126\/science.8316834","article-title":"Benzodiazepine peptidomimetics: Potent inhibitors of Ras farnesylation in animal cells","volume":"260","author":"James","year":"1993","journal-title":"Science"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"22263","DOI":"10.1074\/jbc.270.38.22263","article-title":"Selective inhibition of Ras-dependent cell growth by farnesylthiosalisylic acid","volume":"270","author":"Marom","year":"1995","journal-title":"J. Biol. Chem."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"915140","DOI":"10.1155\/2012\/915140","article-title":"Integrin inhibitors as a therapeutic agent for ovarian cancer","volume":"2012","author":"Sawada","year":"2012","journal-title":"J. Oncol."}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/6\/2\/875\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T21:08:15Z","timestamp":1760216895000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/6\/2\/875"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,2,18]]},"references-count":107,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2014,2]]}},"alternative-id":["v6020875"],"URL":"https:\/\/doi.org\/10.3390\/v6020875","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,2,18]]}}}