Hepatitis C Virus Entry

  • Mirjam B. Zeisel
  • Daniel J. Felmlee
  • Thomas F. BaumertEmail author
Part of the Current Topics in Microbiology and Immunology book series (CT MICROBIOLOGY, volume 369)


Hepatitis C virus (HCV) is a hepatotropic virus and a major cause of chronic hepatitis and liver disease worldwide. Initial interactions between HCV virions and hepatocytes are required for productive viral infection and initiation of the viral life cycle. Furthermore, HCV entry contributes to the tissue tropism and species specificity of this virus. The elucidation of these interactions is critical, not only to understand the pathogenesis of HCV infection, but also to design efficient antiviral strategies and vaccines. This review summarizes our current knowledge of the host factors required for the HCV-host interactions during HCV binding and entry, our understanding of the molecular mechanisms underlying HCV entry into target cells, and the relevance of HCV entry for the pathogenesis of liver disease, antiviral therapy, and vaccine development.


Epidermal Growth Factor Receptor Entry Factor HCVcc Infection Host Cell Kinase 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.





Cluster of differentiation 81


Claudin 1


Epidermal growth factor receptor


Ephrin receptor A2


Hepatitis C virus


Cell culture-derived HCV


HCV-like particles


HCV pseudoparticles


High-density lipoprotein


Immunoglobulin G


Japanese fulminant hepatitis 1


Low-density lipoprotein


Low-density lipoprotein receptor


Liver transplantation


Monoclonal antibody


Niemann-Pick C1-like 1




Protein kinase A


Receptor tyrosine kinases


Scavenger receptor class B type I (alias SCARBI)




Very-low-density lipoprotein



The authors acknowledge financial support of their work by the European Union (ERC-2008-AdG-233130-HEPCENT and INTERREG-IV-FEDER-Hepato-Regio-Net 2009 and 2012), Laboratoire d’Excellence HEPSYS (Investissement d’Avenir; ANR-10-LAB-28), ANRS (2008/354, 2009/183, 2011/132, 2012/239), Inserm, University of Strasbourg and the Strasbourg University Hospitals, France. DJF is a recipient of an EASL fellowship. We also would like to thank Isabel Fofana (Inserm U748, Strasbourg, France) for critical reading of the manuscript.


  1. Agnello V, Abel G, Elfahal M, Knight GB, Zhang QX (1999) Hepatitis C virus and other flaviviridae viruses enter cells via low density lipoprotein receptor. Proc Natl Acad Sci USA 96:12766–12771PubMedGoogle Scholar
  2. Aizaki H, Morikawa K, Fukasawa M, Hara H, Inoue Y, Tani H, Saito K, Nishijima M, Hanada K, Matsuura Y, Lai MM, Miyamura T, Wakita T, Suzuki T (2008) Critical role of virion-associated cholesterol and sphingolipid in hepatitis C virus infection. J Virol 82:5715–5724PubMedGoogle Scholar
  3. Albecka A, Belouzard S, de Beeck AO, Descamps V, Goueslain L, Bertrand-Michel J, Terce F, Duverlie G, Rouille Y, Dubuisson J (2012) Role of low-density lipoprotein receptor in the hepatitis C virus life cycle. Hepatology 55:998–1007PubMedGoogle Scholar
  4. Altmann SW, Davis HR Jr, Yao X, Laverty M, Compton DS, Zhu LJ, Crona JH, Caplen MA, Hoos LM, Tetzloff G, Priestley T, Burnett DA, Strader CD, Graziano MP (2002) The identification of intestinal scavenger receptor class B, type I (SR-BI) by expression cloning and its role in cholesterol absorption. Biochim Biophys Acta 1580:77–93PubMedGoogle Scholar
  5. Andre P, Komurian-Pradel F, Deforges S, Perret M, Berland JL, Sodoyer M, Pol S, Brechot C, Paranhos-Baccala G, Lotteau V (2002) Characterization of low- and very-low-density hepatitis C virus RNA-containing particles. J Virol 76:6919–6928PubMedGoogle Scholar
  6. Andreo U, Maillard P, Kalinina O, Walic M, Meurs E, Martinot M, Marcellin P, Budkowska A (2007) Lipoprotein lipase mediates hepatitis C virus (HCV) cell entry and inhibits HCV infection. Cell Microbiol 9:2445–2456PubMedGoogle Scholar
  7. Appel N, Zayas M, Miller S, Krijnse-Locker J, Schaller T, Friebe P, Kallis S, Engel U, Bartenschlager R (2008) Essential role of domain III of nonstructural protein 5A for hepatitis C virus infectious particle assembly. PLoS Pathog 4:e1000035PubMedGoogle Scholar
  8. Bankwitz D, Steinmann E, Bitzegeio J, Ciesek S, Friesland M, Herrmann E, Zeisel MB, Baumert TF, Keck ZY, Foung SK, Pecheur EI, Pietschmann T (2010) Hepatitis C virus hypervariable region 1 modulates receptor interactions, conceals the CD81 binding site, and protects conserved neutralizing epitopes. J Virol 84:5751–5763PubMedGoogle Scholar
  9. Barth H, Schäfer C, Adah MI, Zhang F, Linhardt RJ, Toyoda H, Kinoshita-Toyoda A, Toida T, Van Kuppevelt TH, Depla E, Weizsäcker FV, Blum HE, Baumert TF (2003) Cellular binding of hepatitis C virus envelope glycoprotein E2 requires cell surface heparan sulfate. J Biol Chem 278:41003–41012PubMedGoogle Scholar
  10. Barth H, Cerino R, Arcuri M, Hoffmann M, Schurmann P, Adah MI, Gissler B, Zhao X, Ghisetti V, Lavezzo B, Blum HE, von Weizsacker F, Vitelli A, Scarselli E, Baumert TF (2005a) Scavenger receptor class B type I and hepatitis C virus infection of primary tupaia hepatocytes. J Virol 79:5774–5785PubMedGoogle Scholar
  11. Barth H, Ulsenheimer A, Pape GR, Diepolder HM, Hoffmann M, Neumann-Haefelin C, Thimme R, Henneke P, Klein R, Paranhos-Baccala G, Depla E, Liang TJ, Blum HE, Baumert TF (2005b) Uptake and presentation of hepatitis C virus-like particles by human dendritic cells. Blood 105:3605–3614PubMedGoogle Scholar
  12. Barth H, Liang TJ, Baumert TF (2006a) Hepatitis C virus entry: molecular biology and clinical implications. Hepatology 44:527–535PubMedGoogle Scholar
  13. Barth H, Schnober EK, Zhang F, Linhardt RJ, Depla E, Boson B, Cosset FL, Patel AH, Blum HE, Baumert TF (2006b) Viral and cellular determinants of the hepatitis C virus envelope-heparan sulfate interaction. J Virol 80:10579–10590PubMedGoogle Scholar
  14. Barth H, Schnober EK, Neumann-Haefelin C, Thumann C, Zeisel MB, Diepolder HM, Hu Z, Liang TJ, Blum HE, Thimme R, Lambotin M, Baumert TF (2008) Scavenger receptor class B is required for hepatitis C virus uptake and cross-presentation by human dendritic cells. J Virol 82:3466–3479PubMedGoogle Scholar
  15. Bartosch B, Dubuisson J, Cosset FL (2003a) Infectious hepatitis C virus pseudo-particles containing functional E1-E2 envelope protein complexes. J Exp Med 197: 633-642. J Exp Med 197:633–642PubMedGoogle Scholar
  16. Bartosch B, Vitelli A, Granier C, Goujon C, Dubuisson J, Pascale S, Scarselli E, Cortese R, Nicosia A, Cosset FL (2003b) Cell entry of hepatitis C virus requires a set of co-receptors that include the CD81 tetraspanin and the SR-B1 scavenger receptor. J Biol Chem 278:41624–41630PubMedGoogle Scholar
  17. Bartosch B, Verney G, Dreux M, Donot P, Morice Y, Penin F, Pawlotsky JM, Lavillette D, Cosset FL (2005) An interplay between hypervariable region 1 of the hepatitis C virus E2 glycoprotein, the scavenger receptor BI, and high-density lipoprotein promotes both enhancement of infection and protection against neutralizing antibodies. J Virol 79:8217–8229PubMedGoogle Scholar
  18. Bartosch B, Cosset FL (2006) Cell entry of hepatitis C virus. Virology 348:1–12PubMedGoogle Scholar
  19. Baumert TF, Ito S, Wong DT, Liang TJ (1998) Hepatitis C virus structural proteins assemble into viruslike particles in insect cells. J Virol 72:3827–3836PubMedGoogle Scholar
  20. Benedicto I, Molina-Jimenez F, Barreiro O, Maldonado-Rodriguez A, Prieto J, Moreno-Otero R, Aldabe R, Lopez-Cabrera M, Majano PL (2008) Hepatitis C virus envelope components alter localization of hepatocyte tight junction-associated proteins and promote occludin retention in the endoplasmic reticulum. Hepatology 48:1044–1053PubMedGoogle Scholar
  21. Benedicto I, Molina-Jimenez F, Bartosch B, Cosset FL, Lavillette D, Prieto J, Moreno-Otero R, Valenzuela-Fernandez A, Aldabe R, Lopez-Cabrera M, Majano PL (2009) The tight junction-associated protein occludin is required for a postbinding step in hepatitis C virus entry and infection. J Virol 83:8012–8020PubMedGoogle Scholar
  22. Benga WJ, Krieger SE, Dimitrova M, Zeisel MB, Parnot M, Lupberger J, Hildt E, Luo G, McLauchlan J, Baumert TF, Schuster C (2010) Apolipoprotein E interacts with hepatitis C virus nonstructural protein 5A and determines assembly of infectious particles. Hepatology 51:43–53PubMedGoogle Scholar
  23. Berneis KK, Krauss RM (2002) Metabolic origins and clinical significance of LDL heterogeneity. J Lipid Res 43:1363–1379PubMedGoogle Scholar
  24. Bertaux C, Dragic T (2006) Different domains of CD81 mediate distinct stages of hepatitis C virus pseudoparticle entry. J Virol 80:4940–4948PubMedGoogle Scholar
  25. Blanchard E, Brand D, Trassard S, Goudeau A, Roingeard P (2002) Hepatitis C virus-like particle morphogenesis. J. Virol. 76:4073–4079PubMedGoogle Scholar
  26. Blanchard E, Belouzard S, Goueslain L, Wakita T, Dubuisson J, Wychowski C, Rouille Y (2006) Hepatitis C virus entry depends on clathrin-mediated endocytosis. J Virol 80:6964–6972PubMedGoogle Scholar
  27. Boriskin YS, Pecheur EI, Polyak SJ (2006) Arbidol: a broad-spectrum antiviral that inhibits acute and chronic HCV infection. Virology J 3:56Google Scholar
  28. Boriskin YS, Leneva IA, Pecheur EI, Polyak SJ (2008) Arbidol: a broad-spectrum antiviral compound that blocks viral fusion. Curr Medicinal Chem 15:997–1005Google Scholar
  29. Boulant S, Targett-Adams P, McLauchlan J (2007) Disrupting the association of hepatitis C virus core protein with lipid droplets correlates with a loss in production of infectious virus. J Gen Virol 88:2204–2213PubMedGoogle Scholar
  30. Bradley D, McCaustland K, Krawczynski K, Spelbring J, Humphrey C, Cook EH (1991) Hepatitis C virus: buoyant density of the factor VIII-derived isolate in sucrose. J Med Virol 34:206–208PubMedGoogle Scholar
  31. Bridge SH, Sheridan DA, Felmlee DJ, Nielsen SU, Thomas HC, Taylor-Robinson SD, Neely RD, Toms GL, Bassendine MF (2011) Insulin resistance and low-density apolipoprotein B-associated lipoviral particles in hepatitis C virus genotype 1 infection. Gut 60:680–687PubMedGoogle Scholar
  32. Brimacombe CL, Grove J, Meredith LW, Hu K, Syder AJ, Flores MV, Timpe JM, Krieger SE, Baumert TF, Tellinghuisen TL, Wong-Staal F, Balfe P, McKeating JA (2011) Neutralizing antibody-resistant hepatitis C virus cell-to-cell transmission. J Virol 85:596–605PubMedGoogle Scholar
  33. Bukh J (2012) Animal models for the study of hepatitis C virus infection and related liver disease. Gastroenterology 142(1279–1287):e1273Google Scholar
  34. Catanese MT, Graziani R, von Hahn T, Moreau M, Huby T, Paonessa G, Santini C, Luzzago A, Rice CM, Cortese R, Vitelli A, Nicosia A (2007) High-avidity monoclonal antibodies against the human scavenger class B type I receptor efficiently block hepatitis C virus infection in the presence of high-density lipoprotein. J Virol 81:8063–8071PubMedGoogle Scholar
  35. Catanese MT, Ansuini H, Graziani R, Huby T, Moreau M, Ball JK, Paonessa G, Rice CM, Cortese R, Vitelli A, Nicosia A (2010) Role of scavenger receptor class B type I in hepatitis C virus entry: kinetics and molecular determinants. J Virol 84:34–43PubMedGoogle Scholar
  36. Chang KS, Jiang J, Cai Z, Luo G (2007) Human apolipoprotein e is required for infectivity and production of hepatitis C virus in cell culture. J Virol 81:13783–13793PubMedGoogle Scholar
  37. Chevaliez S, Asselah T (2011) Mechanisms of non-response to antiviral treatment in chronic hepatitis C. Clin Res Hepatol Gastroenterol 35(Suppl 1):S31–41PubMedGoogle Scholar
  38. Choo Q-L, Kuo A, Weiner AJ, Overby LR, Bradley DW, Houghton M (1989) Isolation of a cDNA clone derived from a blood-borne non-A, non-B viral hepatitis genome. Science 244:359–362PubMedGoogle Scholar
  39. Codran A, Royer C, Jaeck D, Bastien-Valle M, Baumert TF, Kieny MP, Pereira CA, Martin JP (2006) Entry of hepatitis C virus pseudotypes into primary human hepatocytes by clathrin-dependent endocytosis. J Gen Virol 87:2583–2593PubMedGoogle Scholar
  40. Coller KE, Berger KL, Heaton NS, Cooper JD, Yoon R, Randall G (2009) RNA interference and single particle tracking analysis of hepatitis C virus endocytosis. PLoS Pathog 5:e1000702PubMedGoogle Scholar
  41. Cormier EG, Durso RJ, Tsamis F, Boussemart L, Manix C, Olson WC, Gardner JP, Dragic T (2004) L-SIGN (CD209L) and DC-SIGN (CD209) mediate transinfection of liver cells by hepatitis C virus. Proc Natl Acad Sci USA 101:14067–14072PubMedGoogle Scholar
  42. Cukierman L, Meertens L, Bertaux C, Kajumo F, Dragic T (2009) Residues in a highly conserved claudin-1 motif are required for hepatitis C virus entry and mediate the formation of cell-cell contacts. J Virol 83:5477–5484PubMedGoogle Scholar
  43. Cun W, Jiang J, Luo G (2010) The C-terminal alpha-helix domain of apolipoprotein E is required for interaction with nonstructural protein 5A and assembly of hepatitis C virus. J Virol 84:11532–11541PubMedGoogle Scholar
  44. Dao Thi VL, Granier C, Zeisel MB, Guerin M, Mancip J, Granio O, Penin F, Lavillette D, Bartenschlager R, Baumert TF, Cosset FL, Dreux M (2012) Characterization of Hepatitis C Virus Particle Subpopulations Reveals Multiple Usage of the Scavenger Receptor BI for Entry Steps. J Biol Chem 287:31242–31257PubMedGoogle Scholar
  45. Davis GL, Nelson DR, Terrault N, Pruett TL, Schiano TD, Fletcher CV, Sapan CV, Riser LN, Li Y, Whitley RJ, Gnann JW Jr (2005) A randomized, open-label study to evaluate the safety and pharmacokinetics of human hepatitis C immune globulin (Civacir) in liver transplant recipients. Liver Transpl 11:941–949PubMedGoogle Scholar
  46. Dorner M, Horwitz JA, Robbins JB, Barry WT, Feng Q, Mu K, Jones CT, Schoggins JW, Catanese MT, Burton DR, Law M, Rice CM, Ploss A (2011) A genetically humanized mouse model for hepatitis C virus infection. Nature 474:208–211PubMedGoogle Scholar
  47. Dreux M, Pietschmann T, Granier C, Voisset C, Ricard-Blum S, Mangeot PE, Keck Z, Foung S, Vu-Dac N, Dubuisson J, Bartenschlager R, Lavillette D, Cosset FL (2006) High density lipoprotein inhibits hepatitis C virus-neutralizing antibodies by stimulating cell entry via activation of the scavenger receptor BI. J Biol Chem 281:18285–18295PubMedGoogle Scholar
  48. Dreux M, Boson B, Ricard-Blum S, Molle J, Lavillette D, Bartosch B, Pecheur EI, Cosset FL (2007) The Exchangeable Apolipoprotein ApoC-I Promotes Membrane Fusion of Hepatitis C Virus. J Biol Chem 282:32357–32369PubMedGoogle Scholar
  49. Dreux M, Dao Thi VL, Fresquet J, Guerin M, Julia Z, Verney G, Durantel D, Zoulim F, Lavillette D, Cosset FL, Bartosch B (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:e1000310PubMedGoogle Scholar
  50. Drummer HE, Boo I, Poumbourios P (2007) Mutagenesis of a conserved fusion peptide-like motif and membrane-proximal heptad-repeat region of hepatitis C virus glycoprotein E1. J Gen Virol 88:1144–1148PubMedGoogle Scholar
  51. Evans MJ, von Hahn T, Tscherne DM, Syder AJ, Panis M, Wolk B, Hatziioannou T, McKeating JA, Bieniasz PD, Rice CM (2007) Claudin-1 is a hepatitis C virus co-receptor required for a late step in entry. Nature 446:801–805PubMedGoogle Scholar
  52. Fafi-Kremer S, Fofana I, Soulier E, Carolla P, Meuleman P, Leroux-Roels G, Patel AH, Cosset FL, Pessaux P, Doffoel M, Wolf P, Stoll-Keller F, Baumert TF (2010) Viral entry and escape from antibody-mediated neutralization influence hepatitis C virus reinfection in liver transplantation. J Exp Med 207:2019–2031PubMedGoogle Scholar
  53. Farquhar MJ, Harris HJ, Diskar M, Jones S, Mee CJ, Nielsen SU, Brimacombe CL, Molina S, Toms GL, Maurel P, Howl J, Herberg FW, van Ijzendoorn SC, Balfe P, McKeating JA (2008) Protein kinase A-dependent step(s) in hepatitis C virus entry and infectivity. J Virol 82:8797–8811PubMedGoogle Scholar
  54. Farquhar MJ, Hu K, Harris HJ, Davis C, Brimacombe CL, Fletcher SJ, Baumert TF, Rappoport JZ, Balfe P, McKeating JA (2012) Hepatitis C virus induces CD81 and claudin-1 endocytosis. J Virol 86:4305–4316PubMedGoogle Scholar
  55. Felmlee DJ, Sheridan DA, Bridge SH, Nielsen SU, Milne RW, Packard CJ, Caslake MJ, McLauchlan J, Toms GL, Neely RD, Bassendine MF (2010) Intravascular transfer contributes to postprandial increase in numbers of very-low-density hepatitis C virus particles. Gastroenterology 139: 1774-1783, 1783 e1771-1776.Google Scholar
  56. Flint M, Maidens CM, Loomis-Price LD, Shotton C, Dubuisson J, Monk P, Hittingbottom A, Levy S, McKeating J (1999) Characterization of hepatitis C virus E2 glycoprotein interaction with a putative cellular receptor CD81. J. Virol. 73:6235–6244PubMedGoogle Scholar
  57. Fofana I, Krieger SE, Grunert F, Glauben S, Xiao F, Fafi-Kremer S, Soulier E, Royer C, Thumann C, Mee CJ, McKeating JA, Dragic T, Pessaux P, Stoll-Keller F, Schuster C, Thompson J, Baumert TF (2010) Monoclonal anti-claudin 1 antibodies prevent hepatitis C virus infection of primary human hepatocytes. Gastroenterology 39:953–964Google Scholar
  58. Fofana I, Fafi-Kremer S, Carolla P, Fauvelle C, Zahid MN, Turek M, Heydmann L, Cury K, Hayer J, Combet C, Cosset FL, Pietschmann T, Hiet MS, Bartenschlager R, Habersetzer F, Doffoel M, Keck ZY, Foung SKH, Zeisel MB, Stoll-Keller F, Baumert TF (2012) Mutations that alter use of hepatitis C virus cell entry factors mediate escape from neutralizing antibodies. Gastroenterology 143(223–233):e229Google Scholar
  59. Frey SE, Houghton M, Coates S, Abrignani S, Chien D, Rosa D, Pileri P, Ray R, Di Bisceglie AM, Rinella P, Hill H, Wolff MC, Schultze V, Han JH, Scharschmidt B, Belshe RB (2010) Safety and immunogenicity of HCV E1E2 vaccine adjuvanted with MF59 administered to healthy adults. Vaccine 28:6367–6373PubMedGoogle Scholar
  60. Gardner JP, Durso RJ, Arrigale RR, Donovan GP, Maddon PJ, Dragic T, Olson WC (2003) L-SIGN (CD 209L) is a liver-specific capture receptor for hepatitis C virus. Proc Natl Acad Sci USA 100:4498–4503PubMedGoogle Scholar
  61. Garrone P, Fluckiger AC, Mangeot PE, Gauthier E, Dupeyrot-Lacas P, Mancip J, Cangialosi A, Du Chene I, LeGrand R, Mangeot I, Lavillette D, Bellier B, Cosset FL, Tangy F, Klatzmann D, Dalba C (2011) A prime-boost strategy using virus-like particles pseudotyped for HCV proteins triggers broadly neutralizing antibodies in macaques. Sci Transl Med 3: 94ra71.Google Scholar
  62. Gastaminza P, Kapadia SB, Chisari FV (2006) Differential biophysical properties of infectious intracellular and secreted hepatitis C virus particles. J Virol 80:11074–11081PubMedGoogle Scholar
  63. Gastaminza P, Cheng G, Wieland S, Zhong J, Liao W, Chisari FV (2008) Cellular determinants of hepatitis C virus assembly, maturation, degradation, and secretion. J Virol 82:2120–2129PubMedGoogle Scholar
  64. Giang E, Dorner M, Prentoe JC, Dreux M, Evans MJ, Bukh J, Rice CM, Ploss A, Burton DR, Law M (2012) Human broadly neutralizing antibodies to the envelope glycoprotein complex of hepatitis C virus. Proc Natl Acad Sci USA 109:6205–6210PubMedGoogle Scholar
  65. Grove J, Huby T, Stamataki Z, Vanwolleghem T, Meuleman P, Farquhar M, Schwarz A, Moreau M, Owen JS, Leroux-Roels G, Balfe P, McKeating JA (2007) Scavenger receptor BI and BII expression levels modulate Hepatitis C virus infectivity. J Virol 81:3162–3169PubMedGoogle Scholar
  66. Grove J, Nielsen S, Zhong J, Bassendine MF, Drummer HE, Balfe P, McKeating JA (2008) Identification of a residue in hepatitis C virus E2 glycoprotein that determines scavenger receptor BI and CD81 receptor dependency and sensitivity to neutralizing antibodies. J Virol 82:12020–12029PubMedGoogle Scholar
  67. Haberstroh A, Schnober EK, Zeisel MB, Carolla P, Barth H, Blum HE, Cosset FL, Koutsoudakis G, Bartenschlager R, Union A, Depla E, Owsianka A, Patel AH, Schuster C, Stoll-Keller F, Doffoel M, Dreux M, Baumert TF (2008) Neutralizing host responses in hepatitis C virus infection target viral entry at postbinding steps and membrane fusion. Gastroenterology 135(1719–1728):e1711Google Scholar
  68. Haid S, Pietschmann T, Pecheur EI (2009) Low pH-dependent hepatitis C virus membrane fusion depends on E2 integrity, target lipid composition, and density of virus particles. J Biol Chem 284:17657–17667PubMedGoogle Scholar
  69. Halliday J, Klenerman P, Barnes E (2011) Vaccination for hepatitis C virus: closing in on an evasive target. Exp Rev Vaccines 10:659–672Google Scholar
  70. Harris HJ, Farquhar MJ, Mee CJ, Davis C, Reynolds GM, Jennings A, Hu K, Yuan F, Deng H, Hubscher SG, Han JH, Balfe P, McKeating JA (2008) CD81 and claudin 1 coreceptor association: role in hepatitis C virus entry. J Virol 82:5007–5020PubMedGoogle Scholar
  71. Harris HJ, Davis C, Mullins JG, Hu K, Goodall M, Farquhar MJ, Mee CJ, McCaffrey K, Young S, Drummer H, Balfe P, McKeating JA (2010) Claudin association with CD81 defines hepatitis C virus entry. J Biol Chem 285:21092–21102PubMedGoogle Scholar
  72. Hawke RL, Schrieber SJ, Soule TA, Wen Z, Smith PC, Reddy KR, Wahed AS, Belle SH, Afdhal NH, Navarro VJ, Berman J, Liu QY, Doo E, Fried MW (2010) Silymarin ascending multiple oral dosing phase I study in noncirrhotic patients with chronic hepatitis C. J Clin Pharmacol 50:434–449PubMedGoogle Scholar
  73. Helle F, Wychowski C, Vu-Dac N, Gustafson KR, Voisset C, Dubuisson J (2006) Cyanovirin-N inhibits hepatitis C virus entry by binding to envelope protein glycans. J Biol Chem 281:25177–25183PubMedGoogle Scholar
  74. Hijikata M, Shimizu YK, Kato H, Iwamoto A, Shih JW, Alter HJ, Purcell RH, Yoshikura H (1993) Equilibrium centrifugation studies of hepatitis C virus: evidence for circulating immune complexes. J Virol 67:1953–1958PubMedGoogle Scholar
  75. Hishiki T, Shimizu Y, Tobita R, Sugiyama K, Ogawa K, Funami K, Ohsaki Y, Fujimoto T, Takaku H, Wakita T, Baumert TF, Miyanari Y, Shimotohno K (2010) Infectivity of hepatitis C virus is influenced by association with apolipoprotein E isoforms. J Virol 84:12048–12057PubMedGoogle Scholar
  76. Houghton M (2012) Prospects for prophylactic and therapeutic vaccines against the hepatitis C viruses. Immunological Rev 239:99–108Google Scholar
  77. Hsu M, Zhang J, Flint M, Logvinoff C, Cheng-Mayer C, Rice CM, McKeating JA (2003) Hepatitis C virus glycoproteins mediate pH-dependent cell entry of pseudotyped retroviral particles. Proc Natl Acad Sci USA 100:7271–7276PubMedGoogle Scholar
  78. Huang H, Sun F, Owen DM, Li W, Chen Y, Gale M Jr, Ye J (2007) Hepatitis C virus production by human hepatocytes dependent on assembly and secretion of very low-density lipoproteins. Proc Natl Acad Sci USA 104:5848–5853PubMedGoogle Scholar
  79. Jamil H, Chu CH, Dickson JK Jr, Chen Y, Yan M, Biller SA, Gregg RE, Wetterau JR, Gordon DA (1998) Evidence that microsomal triglyceride transfer protein is limiting in the production of apolipoprotein B-containing lipoproteins in hepatic cells. J Lipid Res 39:1448–1454PubMedGoogle Scholar
  80. Jia L, Betters JL, Yu L (2011) Niemann-pick C1-like 1 (NPC1L1) protein in intestinal and hepatic cholesterol transport. Annual Rev Physiol 73:239–259PubMedGoogle Scholar
  81. Jiang J, Luo G (2009) Apolipoprotein E but not B is required for the formation of infectious hepatitis C virus particles. J Virol 83:12680–12691PubMedGoogle Scholar
  82. Jiang J, Cun W, Wu X, Shi Q, Tang H, Luo G (2012) Hepatitis C Virus Attachment Mediated by Apolipoprotein E Binding to Cell Surface Heparan Sulfate. J Virol 86:7256–7267PubMedGoogle Scholar
  83. Jones CT, Catanese MT, Law LM, Khetani SR, Syder AJ, Ploss A, Oh TS, Schoggins JW, MacDonald MR, Bhatia SN, Rice CM (2010) Real-time imaging of hepatitis C virus infection using a fluorescent cell-based reporter system. Nat Biotechnol 28:167–171PubMedGoogle Scholar
  84. Kanto T, Hayashi N, Takehara T, Hagiwara H, Mita E, Naito M, Kasahara A, Fusamoto H, Kamada T (1995) Density analysis of hepatitis C virus particle population in the circulation of infected hosts: implications for virus neutralization or persistence. J Hepatol 22:440–448PubMedGoogle Scholar
  85. Kapadia SB, Barth H, Baumert T, McKeating JA, Chisari FV (2007) Initiation of Hepatitis C Virus Infection Is Dependent on Cholesterol and Cooperativity between CD81 and Scavenger Receptor B Type I. J Virol 81:374–383PubMedGoogle Scholar
  86. Kobayashi M, Bennett MC, Bercot T, Singh IR (2006) Functional analysis of hepatitis C virus envelope proteins, using a cell-cell fusion assay. J Virol 80:1817–1825PubMedGoogle Scholar
  87. Koutsoudakis G, Kaul A, Steinmann E, Kallis S, Lohmann V, Pietschmann T, Bartenschlager R (2006) Characterization of the early steps of hepatitis C virus infection by using luciferase reporter viruses. J Virol 80:5308–5320PubMedGoogle Scholar
  88. Krieger SE, Zeisel MB, Davis C, Thumann C, Harris HJ, Schnober EK, Mee C, Soulier E, Royer C, Lambotin M, Grunert F, Dao Thi VL, Dreux M, Cosset FL, McKeating JA, Schuster C, Baumert TF (2010) Inhibition of hepatitis C virus infection by anti-claudin-1 antibodies is mediated by neutralization of E2-CD81-claudin-1 associations. Hepatology 51:1144–1157PubMedGoogle Scholar
  89. Lacek K, Vercauteren K, Grzyb K, Naddeo M, Verhoye L, Slowikowski MP, Fafi-Kremer S, Patel AH, Baumert TF, Folgori A, Leroux-Roels G, Cortese R, Meuleman P, Nicosia A (2012) Novel human SR-BI antibodies prevent infection and dissemination of HCV in vitro and in humanized mice. J Hepatol 57:17–23PubMedGoogle Scholar
  90. Lavie M, Goffard A, Dubuisson J (2007) Assembly of a functional HCV glycoprotein heterodimer. Current issues in molecular biology 9:71–86PubMedGoogle Scholar
  91. Lavillette D, Bartosch B, Nourrisson D, Verney G, Cosset FL, Penin F, Pecheur EI (2006) Hepatitis C virus glycoproteins mediate low pH-dependent membrane fusion with liposomes. J Biol Chem 281:3909–3917PubMedGoogle Scholar
  92. Lavillette D, Pecheur EI, Donot P, Fresquet J, Molle J, Corbau R, Dreux M, Penin F, Cosset FL (2007) 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. J Virol 81:8752–8765PubMedGoogle Scholar
  93. Law M, Maruyama T, Lewis J, Giang E, Tarr AW, Stamataki Z, Gastaminza P, Chisari FV, Jones IM, Fox RI, Ball JK, McKeating JA, Kneteman NM, Burton DR (2008) Broadly neutralizing antibodies protect against hepatitis C virus quasispecies challenge. Nat Med 14:25–27PubMedGoogle Scholar
  94. Lindenbach BD, Meuleman P, Ploss A, Vanwolleghem T, Syder AJ, McKeating JA, Lanford RE, Feinstone SM, Major ME, Leroux-Roels G, Rice CM (2006) Cell culture-grown hepatitis C virus is infectious in vivo and can be recultured in vitro. Proc Natl Acad Sci USA 103:3805–3809PubMedGoogle Scholar
  95. Lindenbach BD, Thiel HJ, Rice CM (2007) Flaviviridae: the viruses and their replication. In “Fields Virology” (DM Knipe and PM Howley, eds.), pp. 1101-1152. Lippincott-Raven, PhiladelphiaGoogle Scholar
  96. Liu S, Yang W, Shen L, Turner JR, Coyne CB, Wang T (2009) Tight junction proteins claudin-1 and occludin control hepatitis C virus entry and are downregulated during infection to prevent superinfection. J Virol 83:2011–2014PubMedGoogle Scholar
  97. Liu S, McCormick KD, Zhao W, Zhao T, Fan D, Wang T (2012) Human apolipoprotein E peptides inhibit hepatitis C virus entry by blocking virus binding. Hepatology 56:484–491PubMedGoogle Scholar
  98. Lozach PY, Lortat-Jacob H, de Lacroix de Lavalette A, Staropoli I, Foung S, Amara A, Houles C, Fieschi F, Schwartz O, Virelizier JL, Arenzana-Seisdedos F, Altmeyer R (2003) DC-SIGN and L-SIGN are high affinity binding receptors for hepatitis C virus glycoprotein E2. J Biol Chem 278: 20358-20366Google Scholar
  99. Lozach PY, Amara A, Bartosch B, Virelizier JL, Arenzana-Seisdedos F, Cosset FL, Altmeyer R (2004) C-type lectins L-SIGN and DC-SIGN capture and transmit infectious hepatitis C virus pseudotype particles. J Biol Chem 279:32035–32045PubMedGoogle Scholar
  100. Ludwig IS, Lekkerkerker AN, Depla E, Bosman F, Musters RJ, Depraetere S, van Kooyk Y, Geijtenbeek TB (2004) Hepatitis C virus targets DC-SIGN and L-SIGN to escape lysosomal degradation. J Virol 78:8322–8332PubMedGoogle Scholar
  101. Lupberger J, Zeisel MB, Xiao F, Thumann C, Fofana I, Zona L, Davis C, Mee CJ, Turek M, Gorke S, Royer C, Fischer B, Zahid MN, Lavillette D, Fresquet J, Cosset FL, Rothenberg SM, Pietschmann T, Patel AH, Pessaux P, Doffoel M, Raffelsberger W, Poch O, McKeating JA, Brino L, Baumert TF (2011) EGFR and EphA2 are host factors for hepatitis C virus entry and possible targets for antiviral therapy. Nat Med 17:589–595PubMedGoogle Scholar
  102. Maillard P, Huby T, Andreo U, Moreau M, Chapman J, Budkowska A (2006) The interaction of natural hepatitis C virus with human scavenger receptor SR-BI/Cla1 is mediated by ApoB-containing lipoproteins. Faseb J 20:735–737PubMedGoogle Scholar
  103. Maillard P, Walic M, Meuleman P, Roohvand F, Huby T, Le Goff W, Leroux-Roels G, Pecheur EI, Budkowska A (2011) Lipoprotein lipase inhibits hepatitis C virus (HCV) infection by blocking virus cell entry. PLoS ONE 6:e26637PubMedGoogle Scholar
  104. Matsumura T, Hu Z, Kato T, Dreux M, Zhang YY, Imamura M, Hiraga N, Juteau JM, Cosset FL, Chayama K, Vaillant A, Liang TJ (2009) Amphipathic DNA polymers inhibit hepatitis C virus infection by blocking viral entry. Gastroenterology 137:673–681PubMedGoogle Scholar
  105. Mazumdar B, Banerjee A, Meyer K, Ray R (2011) Hepatitis C virus E1 envelope glycoprotein interacts with apolipoproteins in facilitating entry into hepatocytes. Hepatology 54:1149–1156PubMedGoogle Scholar
  106. Mee CJ, Harris HJ, Farquhar MJ, Wilson G, Reynolds G, Davis C, van ISC, Balfe P, McKeating JA (2009) Polarization restricts hepatitis C virus entry into HepG2 hepatoma cells. J Virol 83: 6211-6221Google Scholar
  107. Meertens L, Bertaux C, Dragic T (2006) Hepatitis C virus entry requires a critical postinternalization step and delivery to early endosomes via clathrin-coated vesicles. J Virol 80:11571–11578PubMedGoogle Scholar
  108. Meertens L, Bertaux C, Cukierman L, Cormier E, Lavillette D, Cosset FL, Dragic T (2008) The tight junction proteins claudin-1, -6, and -9 are entry cofactors for hepatitis C virus. J Virol 82:3555–3560PubMedGoogle Scholar
  109. Mensa L, Crespo G, Gastinger MJ, Kabat J, Perez-del-Pulgar S, Miquel R, Emerson SU, Purcell RH, Forns X (2011) Hepatitis C virus receptors claudin-1 and occludin after liver transplantation and influence on early viral kinetics. Hepatology 53:1436–1445PubMedGoogle Scholar
  110. Merz A, Long G, Hiet MS, Brugger B, Chlanda P, Andre P, Wieland F, Krijnse-Locker J, Bartenschlager R (2011) Biochemical and morphological properties of hepatitis C virus particles and determination of their lipidome. J Biol Chem 286:3018–3032PubMedGoogle Scholar
  111. Meuleman P, Hesselgesser J, Paulson M, Vanwolleghem T, Desombere I, Reiser H, Leroux-Roels G (2008) Anti-CD81 antibodies can prevent a hepatitis C virus infection in vivo. Hepatology 48:1761–1768PubMedGoogle Scholar
  112. Meuleman P, Albecka A, Belouzard S, Vercauteren K, Verhoye L, Wychowski C, Leroux-Roels G, Palmer KE, Dubuisson J (2011a) Griffithsin has antiviral activity against hepatitis C virus. Antimicrob Agents Chemother 55:5159–5167PubMedGoogle Scholar
  113. Meuleman P, Bukh J, Verhoye L, Farhoudi A, Vanwolleghem T, Wang RY, Desombere I, Alter H, Purcell RH, Leroux-Roels G (2011b) In vivo evaluation of the cross-genotype neutralizing activity of polyclonal antibodies against hepatitis C virus. Hepatology 53:755–762PubMedGoogle Scholar
  114. Meuleman P, Catanese MT, Verhoye L, Desombere I, Farhoudi A, Jones CT, Sheahan T, Grzyb K, Cortese R, Rice CM, Leroux-Roels G, Nicosia A (2012) A human monoclonal antibody targeting scavenger receptor class B type I precludes hepatitis C virus infection and viral spread in vitro and in vivo. Hepatology 55:364–372PubMedGoogle Scholar
  115. Meunier JC, Russell RS, Engle RE, Faulk KN, Purcell RH, Emerson SU (2008) Apolipoprotein c1 association with hepatitis C virus. J Virol 82:9647–9656PubMedGoogle Scholar
  116. Miyamoto H, Okamoto H, Sato K, Tanaka T, Mishiro S (1992) Extraordinarily low density of hepatitis C virus estimated by sucrose gradient centrifugation and the polymerase chain reaction. J Gen Virol 73:715–718PubMedGoogle Scholar
  117. Miyanari Y, Atsuzawa K, Usuda N, Watashi K, Hishiki T, Zayas M, Bartenschlager R, Wakita T, Hijikata M, Shimotohno K (2007) The lipid droplet is an important organelle for hepatitis C virus production. Nat Cell Biol 9:1089–1097PubMedGoogle Scholar
  118. Monazahian M, Bohme I, Bonk S, Koch A, Scholz C, Grethe S, Thomssen R (1999) Low density lipoprotein receptor as a candidate receptor for hepatitis C virus. J Med Virol 57:223–229PubMedGoogle Scholar
  119. Morikawa K, Zhao Z, Date T, Miyamoto M, Murayama A, Akazawa D, Tanabe J, Sone S, Wakita T (2007) The roles of CD81 and glycosaminoglycans in the adsorption and uptake of infectious HCV particles. J Med Virol 79:714–723PubMedGoogle Scholar
  120. Murray CL, Rice CM (2011) Turning Hepatitis C Virus into a Real Virus. Annual Rev Microbiol 65:307–327Google Scholar
  121. Neumann UP, Biermer M, Eurich D, Neuhaus P, Berg T (2010) Successful prevention of hepatitis C virus (HCV) liver graft reinfection by silibinin mono-therapy. J Hepatol 52:951–952PubMedGoogle Scholar
  122. Nielsen SU, Bassendine MF, Burt AD, Martin C, Pumeechockchai W, Toms GL (2006) Association between hepatitis C virus and very-low-density lipoprotein (VLDL)/LDL analyzed in iodixanol density gradients. J Virol 80:2418–2428PubMedGoogle Scholar
  123. Op De Beeck A, Dubuisson J (2003) Topology of hepatitis C virus envelope glycoproteins. Rev Med Virol 13:233–241PubMedGoogle Scholar
  124. Out R, Hoekstra M, Spijkers JA, Kruijt JK, van Eck M, Bos IS, Twisk J, Van Berkel TJ (2004) Scavenger receptor class B type I is solely responsible for the selective uptake of cholesteryl esters from HDL by the liver and the adrenals in mice. J Lipid Res 45:2088–2095PubMedGoogle Scholar
  125. Owen DM, Huang H, Ye J, Gale M Jr (2009) Apolipoprotein E on hepatitis C virion facilitates infection through interaction with low-density lipoprotein receptor. Virology 394:99–108PubMedGoogle Scholar
  126. Packard CJ, Shepherd J (1997) Lipoprotein heterogeneity and apolipoprotein B metabolism. Arteriosclerosis Thrombosis Vascular Biol 17:3542–3556Google Scholar
  127. Pawlotsky JM (2011) Treatment failure and resistance with direct-acting antiviral drugs against hepatitis C virus. Hepatology 53:1742–1751PubMedGoogle Scholar
  128. Pileri P, Uematsu Y, Campagnoli S, Galli G, Falugi F, Petracca R, Weiner AJ, Houghton M, Rosa D, Grandi G, Abrignani S (1998) Binding of hepatitis C virus to CD81. Science 282:938–941PubMedGoogle Scholar
  129. Ploss A, Evans MJ, Gaysinskaya VA, Panis M, You H, de Jong YP, Rice CM (2009) Human occludin is a hepatitis C virus entry factor required for infection of mouse cells. Nature 457:882–886PubMedGoogle Scholar
  130. Pohlmann S, Zhang J, Baribaud F, Chen Z, Leslie GJ, Lin G, Granelli-Piperno A, Doms RW, Rice CM, McKeating JA (2003) Hepatitis C Virus Glycoproteins Interact with DC-SIGN and DC-SIGNR. J Virol 77:4070–4080PubMedGoogle Scholar
  131. Polyak SJ, Morishima C, Shuhart MC, Wang CC, Liu Y, Lee DY (2007) Inhibition of T-cell inflammatory cytokines, hepatocyte NF-kappaB signaling, and HCV infection by standardized Silymarin. Gastroenterology 132:1925–1936PubMedGoogle Scholar
  132. Prentoe J, Jensen TB, Meuleman P, Serre SB, Scheel TK, Leroux-Roels G, Gottwein JM, Bukh J (2011) Hypervariable region 1 differentially impacts viability of hepatitis C virus strains of genotypes 1 to 6 and impairs virus neutralization. J Virol 85:2224–2234PubMedGoogle Scholar
  133. Price DA, Bassendine MF, Norris SM, Golding C, Toms GL, Schmid ML, Morris CM, Burt AD, Donaldson PT (2006) Apolipoprotein epsilon3 allele is associated with persistent hepatitis C virus infection. Gut 55:715–718PubMedGoogle Scholar
  134. Prince AM, Huima-Byron T, Parker TS, Levine DM (1996) Visualization of hepatitis C virions and putative defective interfering particles isolated from low-density lipoproteins. J Viral Hepat 3:11–17PubMedGoogle Scholar
  135. Reynolds GM, Harris HJ, Jennings A, Hu K, Grove J, Lalor PF, Adams DH, Balfe P, Hubscher SG, McKeating JA (2008) Hepatitis C virus receptor expression in normal and diseased liver tissue. Hepatology 47:418–427PubMedGoogle Scholar
  136. Roingeard P, Hourioux C, Blanchard E, Prensier G (2008) Hepatitis C virus budding at lipid droplet-associated ER membrane visualized by 3D electron microscopy. Histochem Cell Biol 130:561–566PubMedGoogle Scholar
  137. Rothblat GH, Phillips MC (2010) High-density lipoprotein heterogeneity and function in reverse cholesterol transport. Curr Opin Lipidol 21:229–238PubMedGoogle Scholar
  138. Rutter K, Scherzer TM, Beinhardt S, Kerschner H, Stattermayer AF, Hofer H, Popow-Kraupp T, Steindl-Munda P, Ferenci P (2011) Intravenous silibinin as ‘rescue treatment’ for on-treatment non-responders to pegylated interferon/ribavirin combination therapy. Antiviral Therapy 16:1327–1333PubMedGoogle Scholar
  139. Rye KA, Bursill CA, Lambert G, Tabet F, Barter PJ (2009) The metabolism and anti-atherogenic properties of HDL. J Lipid Res 50(Suppl):S195–200PubMedGoogle Scholar
  140. Sainz B Jr, Barretto N, Martin DN, Hiraga N, Imamura M, Hussain S, Marsh KA, Yu X, Chayama K, Alrefai WA, Uprichard SL (2012) Identification of the Niemann-Pick C1-like 1 cholesterol absorption receptor as a new hepatitis C virus entry factor. Nat Med 18:281–285PubMedGoogle Scholar
  141. Saito H, Dhanasekaran P, Nguyen D, Baldwin F, Weisgraber KH, Wehrli S, Phillips MC, Lund-Katz S (2003) Characterization of the heparin binding sites in human apolipoprotein E. J Biol Chem 278:14782–14787PubMedGoogle Scholar
  142. Saunier B, Triyatni M, Ulianich L, Maruvada P, Yen P, Kohn LD (2003) Role of the asialoglycoprotein receptor in binding and entry of hepatitis C virus structural proteins in cultured human hepatocytes. J Virol 77:546–559PubMedGoogle Scholar
  143. Scarselli E, Ansuini H, Cerino R, Roccasecca RM, Acali S, Filocamo G, Traboni C, Nicosia A, Cortese R, Vitelli A (2002) The human scavenger receptor class B type I is a novel candidate receptor for the hepatitis C virus. EMBO J 21:5017–5025PubMedGoogle Scholar
  144. Shachter NS (2001) Apolipoproteins C-I and C-III as important modulators of lipoprotein metabolism. Curr Opin Lipidol 12:297–304PubMedGoogle Scholar
  145. Shelness GS, Sellers JA (2001) Very-low-density lipoprotein assembly and secretion. Curr Opin Lipidol 12:151–157PubMedGoogle Scholar
  146. Shimizu Y, Hishiki T, Sugiyama K, Ogawa K, Funami K, Kato A, Ohsaki Y, Fujimoto T, Takaku H, Shimotohno K (2010) Lipoprotein lipase and hepatic triglyceride lipase reduce the infectivity of hepatitis C virus (HCV) through their catalytic activities on HCV-associated lipoproteins. Virology 407:152–159PubMedGoogle Scholar
  147. Skov M, Tonnesen CK, Hansen GH, Danielsen EM (2011) Dietary cholesterol induces trafficking of intestinal Niemann-Pick Type C1 Like 1 from the brush border to endosomes. Am J Physiol 300:G33–40Google Scholar
  148. Steinmann D, Barth H, Gissler B, Schürmann P, Adah MI, Gerlach JT, Pape GR, Depla E, Jacobs D, Maertens G, Patel AH, Inchauspé G, Liang TJ, Blum HE, Baumert TF (2004) Inhibition of hepatitis C virus-like particle binding to target cells by antiviral antibodies in acute and chronic hepatitis C. J Virol 78:9030–9040PubMedGoogle Scholar
  149. Syder AJ, Lee H, Zeisel MB, Grove J, Soulier E, Macdonald J, Chow S, Chang J, Baumert TF, McKeating JA, McKelvy J, Wong-Staal F (2011) Small molecule scavenger receptor BI antagonists are potent HCV entry inhibitors. J Hepatol 54:48–55PubMedGoogle Scholar
  150. Thomssen R, Bonk S, Propfe C, Heermann K-H, Koechel HG, Uy A (1992) Association of hepatitis C virus in human sera with beta-lipoprotein. Med Microbiol Immunol 181:293–300PubMedGoogle Scholar
  151. Thomssen R, Bonk S, Thiele A (1993) Density heterogeneities of hepatitis C virus in human sera due to the binding of beta-lipoproteins and immunoglobulins. Med Microbiol Immunol 182:329–334PubMedGoogle Scholar
  152. Timpe JM, Stamataki Z, Jennings A, Hu K, Farquhar MJ, Harris HJ, Schwarz A, Desombere I, Roels GL, Balfe P, McKeating JA (2008) Hepatitis C virus cell-cell transmission in hepatoma cells in the presence of neutralizing antibodies. Hepatology 47:17–24PubMedGoogle Scholar
  153. Triyatni M, Saunier B, Maruvada P, Davis AR, Ulianich L, Heller T, Patel A, Kohn LD, Liang TJ (2002) Interaction of hepatitis C virus-like particles and cells: a model system for studying viral binding and entry. J Virol 76:9335–9344PubMedGoogle Scholar
  154. Trotard M, Lepere-Douard C, Regeard M, Piquet-Pellorce C, Lavillette D, Cosset FL, Gripon P, Le Seyec J (2009) Kinases required in hepatitis C virus entry and replication highlighted by small interference RNA screening. Faseb J 23:3780–3789PubMedGoogle Scholar
  155. Tscherne DM, Jones CT, Evans MJ, Lindenbach BD, McKeating JA, Rice CM (2006) Time- and temperature-dependent activation of hepatitis C virus for low-pH-triggered entry. J Virol 80:1734–1741PubMedGoogle Scholar
  156. Tscherne DM, Evans MJ, von Hahn T, Jones CT, Stamataki Z, McKeating JA, Lindenbach BD, Rice CM (2007) Superinfection exclusion in cells infected with hepatitis C virus. J Virol 81:3693–3703PubMedGoogle Scholar
  157. Valasek MA, Weng J, Shaul PW, Anderson RG, Repa JJ (2005) Caveolin-1 is not required for murine intestinal cholesterol transport. J Biol Chem 280:28103–28109PubMedGoogle Scholar
  158. VanCompernolle SE, Wiznycia AV, Rush JR, Dhanasekaran M, Baures PW, Todd SC (2003) Small molecule inhibition of hepatitis C virus E2 binding to CD81. Virology 314:371–380PubMedGoogle Scholar
  159. Vanwolleghem T, Bukh J, Meuleman P, Desombere I, Meunier JC, Alter H, Purcell RH, Leroux-Roels G (2008) Polyclonal immunoglobulins from a chronic hepatitis C virus patient protect human liver-chimeric mice from infection with a homologous hepatitis C virus strain. Hepatology 47:1846–1855PubMedGoogle Scholar
  160. Vieyres G, Dubuisson J, Patel AH (2011) Characterization of antibody-mediated neutralization directed against the hypervariable region 1 of hepatitis C virus E2 glycoprotein. J Gen Virol 92:494–506PubMedGoogle Scholar
  161. Voisset C, Callens N, Blanchard E, Op De Beeck A, Dubuisson J, Vu-Dac N (2005) High density lipoproteins facilitate hepatitis C virus entry through the scavenger receptor class B type I. J Biol Chem 280:7793–7799PubMedGoogle Scholar
  162. Voisset C, Lavie M, Helle F, Op De Beeck A, Bilheu A, Bertrand-Michel J, Terce F, Cocquerel L, Wychowski C, Vu-Dac N, Dubuisson J (2008) Ceramide enrichment of the plasma membrane induces CD81 internalization and inhibits hepatitis C virus entry. Cell Microbiol 10:606–617PubMedGoogle Scholar
  163. von Hahn T, Lindenbach BD, Boullier A, Quehenberger O, Paulson M, Rice CM, McKeating JA (2006) Oxidized low-density lipoprotein inhibits hepatitis C virus cell entry in human hepatoma cells. Hepatology 43:932–942Google Scholar
  164. von Hahn T, Rice CM (2008) Hepatitis C virus entry. J Biol Chem 283:3689–3693Google Scholar
  165. Wagoner J, Negash A, Kane OJ, Martinez LE, Nahmias Y, Bourne N, Owen DM, Grove J, Brimacombe C, McKeating JA, Pecheur EI, Graf TN, Oberlies NH, Lohmann V, Cao F, Tavis JE, Polyak SJ (2010) Multiple effects of silymarin on the hepatitis C virus lifecycle. Hepatology 51:1912–1921PubMedGoogle Scholar
  166. Wang H, Gilham D, Lehner R (2007) Proteomic and lipid characterization of apolipoprotein B-free luminal lipid droplets from mouse liver microsomes: implications for very low density lipoprotein assembly. J Biol Chem 282:33218–33226PubMedGoogle Scholar
  167. Witteveldt J, Evans MJ, Bitzegeio J, Koutsoudakis G, Owsianka AM, Angus AG, Keck ZY, Foung SK, Pietschmann T, Rice CM, Patel AH (2009) CD81 is dispensable for hepatitis C virus cell-to-cell transmission in hepatoma cells. J Gen Virol 90:48–58PubMedGoogle Scholar
  168. Wunschmann S, Medh JD, Klinzmann D, Schmidt WN, Stapleton JT (2000) Characterization of hepatitis C virus (HCV) and HCV E2 interactions with CD81 and the low-density lipoprotein receptor. J Virol 74:10055–10062PubMedGoogle Scholar
  169. Yamamoto M, Aizaki H, Fukasawa M, Teraoka T, Miyamura T, Wakita T, Suzuki T (2011) Structural requirements of virion-associated cholesterol for infectivity, buoyant density and apolipoprotein association of hepatitis C virus. J Gen Virol 92:2082–2087PubMedGoogle Scholar
  170. Yang W, Qiu C, Biswas N, Jin J, Watkins SC, Montelaro RC, Coyne CB, Wang T (2008) Correlation of the tight junction-like distribution of Claudin-1 to the cellular tropism of hepatitis C virus. J Biol Chem 283:8643–8653PubMedGoogle Scholar
  171. Zahid MN, Turek M, Xiao F, Thi VL, Guerin M, Fofana I, Bachellier P, Thompson J, Delang L, Neyts J, Bankwitz D, Pietschmann T, Dreux M, Cosset FL, Grunert F, Baumert TF, Zeisel MB (2012) The post-binding activity of scavenger receptor BI mediates initiation of hepatitis C virus infection and viral dissemination. Hepatology. Oct 18. doi: 10.1002/hep.26097. [Epub ahead of print]Google Scholar
  172. Zeisel MB, Koutsoudakis G, Schnober EK, Haberstroh A, Blum HE, Cosset F-L, Wakita T, Jaeck D, Doffoel M, Royer C, Soulier E, Schvoerer E, Schuster C, Stoll-Keller F, Bartenschlager R, Pietschmann T, Barth H, Baumert TF (2007) Scavenger receptor BI is a key host factor for Hepatitis C virus infection required for an entry step closely linked to CD81. Hepatology 46:1722–1731PubMedGoogle Scholar
  173. Zeisel MB, Fofana I, Fafi-Kremer S, Baumert TF (2011) Hepatitis C virus entry into hepatocytes: Molecular mechanisms and targets for antiviral therapies. J Hepatol 54:566–576PubMedGoogle Scholar
  174. Zeisel MB, Lupberger J, Fofana I, Baumert TF (2012) Host-targeting agents for prevention and treatment of viral hepatitis C - perspectives and challenges. J Hepatol Oct 4. pii: S0168–8278(12)00753-2. doi: 10.1016/j.jhep.2012.09.022. [Epub ahead of print]Google Scholar
  175. Zheng A, Yuan F, Li Y, Zhu F, Hou P, Li J, Song X, Ding M, Deng H (2007) Claudin-6 and claudin-9 function as additional coreceptors for hepatitis C virus. J Virol 81:12465–12471PubMedGoogle Scholar
  176. Zheng C, Khoo C, Furtado J, Ikewaki K, Sacks FM (2008) Dietary monounsaturated fat activates metabolic pathways for triglyceride-rich lipoproteins that involve apolipoproteins E and C-III. Am J Clin Nutri 88:272–281Google Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Mirjam B. Zeisel
    • 1
    • 2
  • Daniel J. Felmlee
    • 1
    • 2
  • Thomas F. Baumert
    • 1
    • 2
    • 3
    Email author
  1. 1.Inserm, U1110StrasbourgFrance
  2. 2.University of StrasbourgStrasbourgFrance
  3. 3.Pôle Hépato-digestif Hôpitaux Universitaires de StrasbourgStrasbourgFrance

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