Genetic diversity underlying the envelope glycoproteins of hepatitis C virus: Structural and functional consequences and the implications for vaccine design

Viruses

Volumn 7, Issue 7, 2015, Pages 3995-4046

  Tarr, Alexander W ^a   Khera, Tanvi ^b   Hueging, Kathrin ^b   Sheldon, Julie ^b   Steinmann, Eike ^b   Pietschmann, Thomas ^b,c   Brown, Richard J P ^b  

^a UNIVERSITY OF NOTTINGHAM   (United Kingdom)

^b INSTITUTE OF INFECTION IMMUNOLOGY   (Germany)

^c HELMHOLTZ CENTRE FOR INFECTION RESEARCH   (Germany)

Author keywords

Antigenicity; Diversity; Evolution; Functionality; Glycoproteins; HCV; Structure; Vaccine

Indexed keywords

CIGB 230; DNA VACCINE; GLYCOPROTEIN; GLYCOPROTEIN E1; GLYCOPROTEIN E2; HEPATITIS C VACCINE; INTERFERON; NEUTRALIZING ANTIBODY; RECOMBINANT PROTEIN; RITUXIMAB; UNCLASSIFIED DRUG; VIRUS VECTOR; HEPATITIS VACCINE; VIRUS ENVELOPE PROTEIN;

ANTIGENICITY; DRUG DESIGN; GENETIC VARIABILITY; HEPATITIS C; HEPATITIS C VIRUS; HUMAN; IMMUNE EVASION; IMMUNE RESPONSE; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PROTEIN STRUCTURE; REVIEW; SEQUENCE ANALYSIS; VIRUS ENTRY; VIRUS INACTIVATION; VIRUS LIKE AGENT; ANIMAL; CHEMISTRY; GENETIC VARIATION; GENETICS; HEPACIVIRUS; IMMUNOLOGY; VIROLOGY;

HEPATITIS C VIRUS;

ANIMALS; GENETIC VARIATION; HEPACIVIRUS; HEPATITIS C; HUMANS; VIRAL ENVELOPE PROTEINS; VIRAL HEPATITIS VACCINES;

EID: 84937458498     PISSN: None     EISSN: 19994915     Source Type: Journal    
DOI: 10.3390/v7072809     Document Type: Review

References (315)

1. Choo, Q.L.; Kuo, G.; Weiner, A.J.; Overby, L.R.; Bradley, D.W.; Houghton, M. Isolation of a cDNA clone derived from a blood-borne non-A, non-B viral hepatitis genome. Science 1989, 244, 359–362. [CrossRef] [PubMed]
2. Pfaender, S.; Brown, R.J.P.; Pietschmann, T. Natural reservoirs for homologs of hepatitis C virus. Emerg. Microbes Infect. 2014, 3, e21. [CrossRef] [PubMed]
3. Von Schaewen, M.; Ploss, A. Murine models of hepatitis C: What can we look forward to? Antivir. Res. 2014, 104, 15–22. [CrossRef] [PubMed]
4. Shepard, C.W.; Finelli, L.; Alter, M.J. Global epidemiology of hepatitis C virus infection. Lancet Infect. Dis. 2005, 5, 558–567. [CrossRef]
5. Gower, E.; Estes, C.; Blach, S.; Razavi-Shearer, K.; Razavi, H. Global epidemiology and genotype distribution of the hepatitis C virus infection. J. Hepatol. 2014, 61(Suppl. S1), S45–S57. [CrossRef] [PubMed]
6. Vieyres, G.; Thomas, X.; Descamps, V.; Duverlie, G.; Patel, A.H.; Dubuisson, J. Characterization of the envelope glycoproteins associated with infectious hepatitis C virus. J. Virol. 2010, 84, 10159–10168. [CrossRef] [PubMed]
7. Blanchard, E.; Belouzard, S.; Goueslain, L.; Wakita, T.; Dubuisson, J.; Wychowski, C.; Rouille, Y. Hepatitis C virus entry depends on clathrin-mediated endocytosis. J. Virol. 2006, 80, 6964–6972. [CrossRef] [PubMed]
8. Meertens, L.; Bertaux, C.; Dragic, T. Hepatitis C virus entry requires a critical postinternalization step and delivery to early endosomes via clathrin-coated vesicles. J. Virol. 2006, 80, 11571–11578. [CrossRef] [PubMed]
9. Tscherne, D.M.; Jones, C.T.; Evans, M.J.; Lindenbach, B.D.; McKeating, J.A.; Rice, C.M. Time- and temperature-dependent activation of hepatitis C virus for low-pH-triggered entry. J. Virol. 2006, 80, 1734–1741. [CrossRef] [PubMed]
10. Bartosch, B.; Dubuisson, J.; Cosset, F.L. Infectious hepatitis C virus pseudo-particles containing functional E1-E2 envelope protein complexes. J. Exp. Med. 2003, 197, 633–642. [CrossRef] [PubMed]
11. Lavillette, D.; Tarr, A.W.; Voisset, C.; Donot, P.; Bartosch, B.; Bain, C.; Patel, A.H.; Dubuisson, J.; Ball, J.K.; Cosset, F.L. Characterization of host-range and cell entry properties of the major genotypes and subtypes of hepatitis C virus. Hepatology 2005, 41, 265–274. [CrossRef] [PubMed]
12. Hsu, M.; Zhang, J.; Flint, M.; Logvinoff, C.; Cheng-Mayer, C.; Rice, C.M.; McKeating, J.A. Hepatitis C virus glycoproteins mediate pH-dependent cell entry of pseudotyped retroviral particles. Proc. Natl. Acad. Sci. USA 2003, 100, 7271–7276. [CrossRef] [PubMed]
13. Pileri, P.; Uematsu, Y.; Campagnoli, S.; Galli, G.; Falugi, F.; Petracca, R.; Weiner, A.J.; Houghton, M.; Rosa, D.; Grandi, G., et al. Binding of hepatitis C virus to CD81. Science 1998, 282, 938–941. [CrossRef] [PubMed]
14. Scarselli, E.; Ansuini, H.; Cerino, R.; Roccasecca, R.M.; Acali, S.; Filocamo, G.; Traboni, C.; Nicosia, A.; Cortese, R.; Vitelli, A. The human scavenger receptor class B type I is a novel candidate receptor for the hepatitis C virus. EMBO J. 2002, 21, 5017–5025. [CrossRef] [PubMed]
15. Cocquerel, L.; Meunier, J.C.; Op de Beeck, A.; Bonte, D.; Wychowski, C.; Dubuisson, J. Coexpression of hepatitis C virus envelope proteins E1 and E2 in cis improves the stability of membrane insertion of E2. J. Gen. Virol. 2001, 82, 1629–1635. [PubMed]
16. Cocquerel, L.; Wychowski, C.; Minner, F.; Penin, F.; Dubuisson, J. Charged residues in the transmembrane domains of hepatitis C virus glycoproteins play a major role in the processing, subcellular localization, and assembly of these envelope proteins. J. Virol. 2000, 74, 3623–3633. [CrossRef] [PubMed]
17. Albecka, A.; Montserret, R.; Krey, T.; Tarr, A.W.; Diesis, E.; Ball, J.K.; Descamps, V.; Duverlie, G.; Rey, F.; Penin, F., et al. Identification of new functional regions in hepatitis C virus envelope glycoprotein E2. J. Virol. 2011, 85, 1777–1792. [CrossRef] [PubMed]
18. Li, R.; Qin, Y.; He, Y.; Tao, W.; Zhang, N.; Tsai, C.; Zhou, P.; Zhong, J. Production of hepatitis C virus lacking the envelope-encoding genes for single-cycle infection by providing homologous envelope proteins or vesicular stomatitis virus glycoproteins in trans. J. Virol. 2011, 85, 2138–2147. [CrossRef] [PubMed]
19. Doerrbecker, J.; Friesland, M.; Riebesehl, N.; Ginkel, C.; Behrendt, P.; Brown, R.J.; Ciesek, S.; Wedemeyer, H.; Sarrazin, C.; Kaderali, L., et al. Incorporation of primary patient-derived glycoproteins into authentic infectious hepatitis C virus particles. Hepatology 2014, 60, 508–520. [CrossRef] [PubMed]
20. Fournier, C.; Helle, F.; Descamps, V.; Morel, V.; Francois, C.; Dedeurwaerder, S.; Wychowski, C.; Duverlie, G.; Castelain, S. Natural selection of adaptive mutations in non-structural genes increases trans-encapsidation of hepatitis C virus replicons lacking envelope protein genes. J. Gen. Virol. 2013, 94, 996–1008. [CrossRef] [PubMed]
21. Adair, R.; Patel, A.H.; Corless, L.; Griffin, S.; Rowlands, D.J.; McCormick, C.J. Expression of hepatitis C virus (HCV) structural proteins in trans facilitates encapsidation and transmission of HCV subgenomic RNA. J. Gen. Virol. 2009, 90, 833–842. [CrossRef] [PubMed]
22. Steinmann, E.; Brohm, C.; Kallis, S.; Bartenschlager, R.; Pietschmann, T. Efficient trans-encapsidation of hepatitis C virus RNAs into infectious virus-like particles. J. Virol. 2008, 82, 7034–7046. [CrossRef] [PubMed]
23. Ciczora, Y.; Callens, N.; Montpellier, C.; Bartosch, B.; Cosset, F.L.; Op de Beeck, A.; Dubuisson, J. Contribution of the charged residues of hepatitis C virus glycoprotein E2 transmembrane domain to the functions of the E1E2 heterodimer. J. Gen. Virol. 2005, 86, 2793–2798. [CrossRef] [PubMed]
24. Cocquerel, L.; Meunier, J.C.; Pillez, A.; Wychowski, C.; Dubuisson, J. A retention signal necessary and sufficient for endoplasmic reticulum localization maps to the transmembrane domain of hepatitis C virus glycoprotein E2. J. Virol. 1998, 72, 2183–2191. [PubMed]
25. Ciczora, Y.; Callens, N.; Penin, F.; Pecheur, E.I.; Dubuisson, J. Transmembrane domains of hepatitis C virus envelope glycoproteins: Residues involved in E1E2 heterodimerization and involvement of these domains in virus entry. J. Virol. 2007, 81, 2372–2381. [CrossRef] [PubMed]
26. Op de Beeck, A.; Montserret, R.; Duvet, S.; Cocquerel, L.; Cacan, R.; Barberot, B.; Le Maire, M.; Penin, F.; Dubuisson, J. The transmembrane domains of hepatitis C virus envelope glycoproteins E1 and E2 play a major role in heterodimerization. J. Biol. Chem. 2000, 275, 31428–31437. [CrossRef] [PubMed]
27. Douam, F.; Dao Thi, V.L.; Maurin, G.; Fresquet, J.; Mompelat, D.; Zeisel, M.B.; Baumert, T.F.; Cosset, F.L.; Lavillette, D. Critical interaction between E1 and E2 glycoproteins determines binding and fusion properties of hepatitis C virus during cell entry. Hepatology 2014, 59, 776–788. [CrossRef] [PubMed]
28. Meunier, J.C.; Fournillier, A.; Choukhi, A.; Cahour, A.; Cocquerel, L.; Dubuisson, J.; Wychowski, C. Analysis of the glycosylation sites of hepatitis C virus (HCV) glycoprotein E1 and the influence of E1 glycans on the formation of the HCV glycoprotein complex. J. Gen. Virol. 1999, 80, 887–896. [PubMed]
29. Goffard, A.; Callens, N.; Bartosch, B.; Wychowski, C.; Cosset, F.L.; Montpellier, C.; Dubuisson, J. Role of N-linked glycans in the functions of hepatitis C virus envelope glycoproteins. J. Virol. 2005, 79, 8400–8409. [CrossRef] [PubMed]
30. Brown, K.S.; Keogh, M.J.; Owsianka, A.M.; Adair, R.; Patel, A.H.; Arnold, J.N.; Ball, J.K.; Sim, R.B.; Tarr, A.W.; Hickling, T.P. Specific interaction of hepatitis C virus glycoproteins with mannan binding lectin inhibits virus entry. Protein Cell 2010, 1, 664–674. [CrossRef] [PubMed]
31. McCaffrey, K.; Boo, I.; Tewierek, K.; Edmunds, M.L.; Poumbourios, P.; Drummer, H.E. Role of conserved cysteine residues in hepatitis C virus glycoprotein e2 folding and function. J. Virol. 2012, 86, 3961–3974. [CrossRef] [PubMed]
32. Wahid, A.; Helle, F.; Descamps, V.; Duverlie, G.; Penin, F.; Dubuisson, J. Disulfide bonds in hepatitis C virus glycoprotein E1 control the assembly and entry functions of E2 glycoprotein. J. Virol. 2013, 87, 1605–1617. [CrossRef] [PubMed]
33. Lee, J.Y.; Acosta, E.G.; Stoeck, I.K.; Long, G.; Hiet, M.S.; Mueller, B.; Fackler, O.T.; Kallis, S.; Bartenschlager, R. Apolipoprotein E likely contributes to a maturation step of infectious hepatitis C virus particles and interacts with viral envelope glycoproteins. J. Virol. 2014, 88, 12422–12437. [CrossRef] [PubMed]
34. Brazzoli, M.; Helenius, A.; Foung, S.K.; Houghton, M.; Abrignani, S.; Merola, M. Folding and dimerization of hepatitis C virus E1 and E2 glycoproteins in stably transfected CHO cells. Virology 2005, 332, 438–453. [CrossRef] [PubMed]
35. Wakita, T.; Pietschmann, T.; Kato, T.; Date, T.; Miyamoto, M.; Zhao, Z.; Murthy, K.; Habermann, A.; Krausslich, H.G.; Mizokami, M., et al. Production of infectious hepatitis C virus in tissue culture from a cloned viral genome. Nat. Med. 2005, 11, 791–796. [CrossRef] [PubMed]
36. Sandrin, V.; Boulanger, P.; Penin, F.; Granier, C.; Cosset, F.L.; Bartosch, B. Assembly of functional hepatitis C virus glycoproteins on infectious pseudoparticles occurs intracellularly and requires concomitant incorporation of E1 and E2 glycoproteins. J. Gen. Virol. 2005, 86, 3189–3199. [CrossRef] [PubMed]
37. Yagnik, A.T.; Lahm, A.; Meola, A.; Roccasecca, R.M.; Ercole, B.B.; Nicosia, A.; Tramontano, A. A model for the hepatitis C virus envelope glycoprotein E2. Proteins 2000, 40, 355–366. [CrossRef]
38. Flint, M.; Thomas, J.M.; Maidens, C.M.; Shotton, C.; Levy, S.; Barclay, W.S.; McKeating, J.A. Functional analysis of cell surface-expressed hepatitis C virus E2 glycoprotein. J. Virol. 1999, 73, 6782–6790. [PubMed]
39. Modis, Y.; Ogata, S.; Clements, D.; Harrison, S.C. A ligand-binding pocket in the dengue virus envelope glycoprotein. Proc. Natl. Acad. Sci. USA 2003, 100, 6986–6991. [CrossRef] [PubMed]
40. Modis, Y.; Ogata, S.; Clements, D.; Harrison, S.C. Structure of the dengue virus envelope protein after membrane fusion. Nature 2004, 427, 313–319. [CrossRef] [PubMed]
41. Krey, T.; d’Alayer, J.; Kikuti, C.M.; Saulnier, A.; Damier-Piolle, L.; Petitpas, I.; Johansson, D.X.; Tawar, R.G.; Baron, B.; Robert, B., et al. The disulfide bonds in glycoprotein E2 of hepatitis C virus reveal the tertiary organization of the molecule. PLoS Pathog. 2010, 6, e1000762. [CrossRef] [PubMed]
42. Kong, L.; Giang, E.; Nieusma, T.; Kadam, R.U.; Cogburn, K.E.; Hua, Y.; Dai, X.; Stanfield, R.L.; Burton, D.R.; Ward, A.B., et al. Hepatitis C virus E2 envelope glycoprotein core structure. Science 2013, 342, 1090–1094. [CrossRef] [PubMed]
43. Li, H.F.; Huang, C.H.; Ai, L.S.; Chuang, C.K.; Chen, S.S. Mutagenesis of the fusion peptide-like domain of hepatitis C virus E1 glycoprotein: Involvement in cell fusion and virus entry. J. Biomed. Sci. 2009, 16, e89. [CrossRef] [PubMed]
44. Drummer, H.E.; Boo, I.; Poumbourios, P. Mutagenesis of a conserved fusion peptide-like motif and membrane-proximal heptad-repeat region of hepatitis C virus glycoprotein E1. J. Gen. Virol. 2007, 88, 1144–1148. [CrossRef] [PubMed]
45. Spadaccini, R.; D’Errico, G.; D’Alessio, V.; Notomista, E.; Bianchi, A.; Merola, M.; Picone, D. Structural characterization of the transmembrane proximal region of the hepatitis C virus E1 glycoprotein. Biochim. Biophys. Acta 2010, 1798, 344–353. [CrossRef] [PubMed]
46. Russell, R.S.; Kawaguchi, K.; Meunier, J.C.; Takikawa, S.; Faulk, K.; Bukh, J.; Purcell, R.H.; Emerson, S.U. Mutational analysis of the hepatitis C virus E1 glycoprotein in retroviral pseudoparticles and cell-culture-derived H77/JFH1 chimeric infectious virus particles. J. Viral Hepat. 2009, 16, 621–632. [CrossRef] [PubMed]
47. Li, Y.; Wang, J.; Kanai, R.; Modis, Y. Crystal structure of glycoprotein E2 from bovine viral diarrhea virus. Proc. Natl. Acad. Sci. USA 2013, 110, 6805–6810. [CrossRef] [PubMed]
48. El Omari, K.; Iourin, O.; Harlos, K.; Grimes, J.M.; Stuart, D.I. Structure of a pestivirus envelope glycoprotein E2 clarifies its role in cell entry. Cell Rep. 2013, 3, 30–35. [CrossRef] [PubMed]
49. Khan, A.G.; Whidby, J.; Miller, M.T.; Scarborough, H.; Zatorski, A.V.; Cygan, A.; Price, A.A.; Yost, S.A.; Bohannon, C.D.; Jacob, J., et al. Structure of the core ectodomain of the hepatitis C virus envelope glycoprotein 2. Nature 2014, 509, 381–384. [CrossRef] [PubMed]
50. Catanese, M.T.; Uryu, K.; Kopp, M.; Edwards, T.J.; Andrus, L.; Rice, W.J.; Silvestry, M.; Kuhn, R.J.; Rice, C.M. Ultrastructural analysis of hepatitis C virus particles. Proc. Natl. Acad. Sci. USA 2013, 110, 9505–9510. [CrossRef] [PubMed]
51. Gastaminza, P.; Dryden, K.A.; Boyd, B.; Wood, M.R.; Law, M.; Yeager, M.; Chisari, F.V. Ultrastructural and biophysical characterization of hepatitis C virus particles produced in cell culture. J. Virol. 2010, 84, 10999–11009. [CrossRef] [PubMed]
52. Owsianka, A.M.; Timms, J.M.; Tarr, A.W.; Brown, R.J.; Hickling, T.P.; Szwejk, A.; Bienkowska-Szewczyk, K.; Thomson, B.J.; Patel, A.H.; Ball, J.K. Identification of conserved residues in the E2 envelope glycoprotein of the hepatitis C virus that are critical for CD81 binding. J. Virol. 2006, 80, 8695–8704. [CrossRef] [PubMed]
53. Rothwangl, K.B.; Manicassamy, B.; Uprichard, S.L.; Rong, L. Dissecting the role of putative CD81 binding regions of E2 in mediating HCV entry: Putative CD81 binding region 1 is not involved in CD81 binding. Virol. J. 2008, 5, e46. [CrossRef] [PubMed]
54. Lavie, M.; Sarrazin, S.; Montserret, R.; Descamps, V.; Baumert, T.F.; Duverlie, G.; Seron, K.; Penin, F.; Dubuisson, J. Identification of conserved residues in hepatitis C virus envelope glycoprotein E2 that modulate virus dependence on CD81 and SRB1 entry factors. J. Virol. 2014, 88, 10584–10597. [CrossRef] [PubMed]
55. Bankwitz, D.; Steinmann, E.; Bitzegeio, J.; Ciesek, S.; Friesland, M.; Herrmann, E.; Zeisel, M.B.; Baumert, T.F.; Keck, Z.Y.; Foung, S.K., et al. Hepatitis C virus hypervariable region 1 modulates receptor interactions, conceals the CD81 binding site, and protects conserved neutralizing epitopes. J. Virol. 2010, 84, 5751–5763. [CrossRef] [PubMed]
56. Bankwitz, D.; Vieyres, G.; Hueging, K.; Bitzegeio, J.; Doepke, M.; Chhatwal, P.; Haid, S.; Catanese, M.T.; Zeisel, M.B.; Nicosia, A., et al. Role of hypervariable region 1 for the interplay of hepatitis C virus with entry factors and lipoproteins. J. Virol. 2014, 88, 12644–12655. [CrossRef] [PubMed]
57. Bartosch, B.; Verney, G.; Dreux, M.; Donot, P.; Morice, Y.; Penin, F.; Pawlotsky, J.M.; Lavillette, D.; Cosset, F.L. 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. 2005, 79, 8217–8229. [CrossRef] [PubMed]
58. Callens, N.; Ciczora, Y.; Bartosch, B.; Vu-Dac, N.; Cosset, F.L.; Pawlotsky, J.M.; Penin, F.; Dubuisson, J. Basic residues in hypervariable region 1 of hepatitis C virus envelope glycoprotein e2 contribute to virus entry. J. Virol. 2005, 79, 15331–15341. [CrossRef] [PubMed]
59. Guan, M.; Wang, W.; Liu, X.; Tong, Y.; Liu, Y.; Ren, H.; Zhu, S.; Dubuisson, J.; Baumert, T.F.; Zhu, Y., et al. Three different functional microdomains in the hepatitis C virus hypervariable region 1 (HVR1) mediate entry and immune evasion. J. Biol. Chem. 2012, 287, 35631–35645. [CrossRef] [PubMed]
60. Tarr, A.W.; Owsianka, A.M.; Jayaraj, D.; Brown, R.J.; Hickling, T.P.; Irving, W.L.; Patel, A.H.; Ball, J.K. Determination of the human antibody response to the epitope defined by the hepatitis C virus-neutralizing monoclonal antibody AP33. J. Gen. Virol. 2007, 88, 2991–3001. [CrossRef] [PubMed]
61. Tarr, A.W.; Urbanowicz, R.A.; Jayaraj, D.; Brown, R.J.; McKeating, J.A.; Irving, W.L.; Ball, J.K. Naturally occurring antibodies that recognize linear epitopes in the amino terminus of the hepatitis C virus E2 protein confer noninterfering, additive neutralization. J. Virol. 2012, 86, 2739–2749. [CrossRef] [PubMed]
62. Meola, A.; Tarr, A.W.; England, P.; Meredith, L.W.; McClure, C.P.; Foung, S.K.; McKeating, J.A.; Ball, J.K.; Rey, F.A.; Krey, T. Structural flexibility of a conserved antigenic region in hepatitis C virus glycoprotein e2 recognized by broadly neutralizing antibodies. J. Virol. 2015, 89, 2170–2181. [CrossRef] [PubMed]
63. Potter, J.A.; Owsianka, A.M.; Jeffery, N.; Matthews, D.J.; Keck, Z.Y.; Lau, P.; Foung, S.K.; Taylor, G.L.; Patel, A.H. Toward a hepatitis C virus vaccine: The structural basis of hepatitis C virus neutralization by AP33, a broadly neutralizing antibody. J. Virol. 2012, 86, 12923–12932. [CrossRef] [PubMed]
64. Kong, L.; Giang, E.; Nieusma, T.; Robbins, J.B.; Deller, M.C.; Stanfield, R.L.; Wilson, I.A.; Law, M. Structure of hepatitis C virus envelope glycoprotein E2 antigenic site 412 to 423 in complex with antibody AP33. J. Virol. 2012, 86, 13085–13088. [CrossRef] [PubMed]
65. Kong, L.; Giang, E.; Robbins, J.B.; Stanfield, R.L.; Burton, D.R.; Wilson, I.A.; Law, M. Structural basis of hepatitis C virus neutralization by broadly neutralizing antibody HCV1. Proc. Natl. Acad. Sci. USA 2012, 109, 9499–9504. [CrossRef] [PubMed]
66. Li, Y.; Pierce, B.G.; Wang, Q.; Keck, Z.Y.; Fuerst, T.R.; Foung, S.K.; Mariuzza, R.A. Structural basis for penetration of the glycan shield of hepatitis c virus e2 glycoprotein by a broadly neutralizing human antibody. J. Biol. Chem. 2015, 290, 10117–10125. [CrossRef] [PubMed]
67. Rey, F.A.; Heinz, F.X.; Mandl, C.; Kunz, C.; Harrison, S.C. The envelope glycoprotein from tick-borne encephalitis virus at 2 A resolution. Nature 1995, 375, 291–298. [CrossRef] [PubMed]
68. Fournillier Jacob, A.; Cahour, A.; Escriou, N.; Girard, M.; Wychowski, C. Processing of the E1 glycoprotein of hepatitis C virus expressed in mammalian cells. J. Gen. Virol. 1996, 77, 1055–1064. [CrossRef] [PubMed]
69. Ciccaglione, A.R.; Marcantonio, C.; Costantino, A.; Equestre, M.; Geraci, A.; Rapicetta, M. Hepatitis C virus E1 protein induces modification of membrane permeability in E. coli cells. Virology 1998, 250, 1–8. [CrossRef] [PubMed]
70. Merola, M.; Brazzoli, M.; Cocchiarella, F.; Heile, J.M.; Helenius, A.; Weiner, A.J.; Houghton, M.; Abrignani, S. Folding of hepatitis C virus E1 glycoprotein in a cell-free system. J. Virol. 2001, 75, 11205–11217. [CrossRef] [PubMed]
71. El Omari, K.; Iourin, O.; Kadlec, J.; Sutton, G.; Harlos, K.; Grimes, J.M.; Stuart, D.I. Unexpected structure for the N-terminal domain of hepatitis C virus envelope glycoprotein E1. Nat. Commun. 2014, 5, e4874. [CrossRef] [PubMed]
72. Radford, A.D.; Chapman, D.; Dixon, L.; Chantrey, J.; Darby, A.C.; Hall, N. Application of next-generation sequencing technologies in virology. J. Gen. Virol. 2012, 93, 1853–1868. [CrossRef] [PubMed]
73. Suthar, A.B.; Harries, A.D. A public health approach to hepatitis C control in low- and middle-income countries. PLoS Med. 2015, 12, e1001795. [CrossRef] [PubMed]
74. Mazumdar, B.; Banerjee, A.; Meyer, K.; Ray, R. Hepatitis C virus E1 envelope glycoprotein interacts with apolipoproteins in facilitating entry into hepatocytes. Hepatology 2011, 54, 1149–1156. [CrossRef] [PubMed]
75. Grove, J.; Nielsen, S.; Zhong, J.; Bassendine, M.F.; Drummer, H.E.; Balfe, P.; McKeating, J.A. 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. 2008, 82, 12020–12029. [CrossRef] [PubMed]
76. Drummer, H.E.; Boo, I.; Maerz, A.L.; Poumbourios, P. A conserved Gly436-Trp-Leu-Ala-Gly-Leu-Phe-Tyr motif in hepatitis C virus glycoprotein E2 is a determinant of CD81 binding and viral entry. J. Virol. 2006, 80, 7844–7853. [CrossRef] [PubMed]
77. Brown, R.J.; Tarr, A.W.; McClure, C.P.; Juttla, V.S.; Tagiuri, N.; Irving, W.L.; Ball, J.K. Cross-genotype characterization of genetic diversity and molecular adaptation in hepatitis C virus envelope glycoprotein genes. J. Gen. Virol. 2007, 88, 458–469. [CrossRef] [PubMed]
78. Lindenbach, B.D.; Evans, M.J.; Syder, A.J.; Wolk, B.; Tellinghuisen, T.L.; Liu, C.C.; Maruyama, T.; Hynes, R.O.; Burton, D.R.; McKeating, J.A., et al. Complete replication of hepatitis C virus in cell culture. Science 2005, 309, 623–626. [CrossRef] [PubMed]
79. Simmonds, P.; Bukh, J.; Combet, C.; Deleage, G.; Enomoto, N.; Feinstone, S.; Halfon, P.; Inchauspe, G.; Kuiken, C.; Maertens, G., et al. Consensus proposals for a unified system of nomenclature of hepatitis C virus genotypes. Hepatology 2005, 42, 962–973. [CrossRef] [PubMed]
80. Smith, D.B.; Bukh, J.; Kuiken, C.; Muerhoff, A.S.; Rice, C.M.; Stapleton, J.T.; Simmonds, P. Expanded classification of hepatitis C virus into 7 genotypes and 67 subtypes: Updated criteria and genotype assignment web resource. Hepatology 2014, 59, 318–327. [CrossRef] [PubMed]
81. Gravitz, L. Introduction: A smouldering public-health crisis. Nature 2011, 474, S2–S4. [CrossRef] [PubMed]
82. Messina, J.P.; Humphreys, I.; Flaxman, A.; Brown, A.; Cooke, G.S.; Pybus, O.G.; Barnes, E. Global distribution and prevalence of hepatitis C virus genotypes. Hepatology 2015, 61, 77–87. [CrossRef] [PubMed]
83. Alter, M.J. Epidemiology of hepatitis C virus infection. World J. Gastroenterol. 2007, 13, 2436–2441. [CrossRef] [PubMed]
84. Magiorkinis, G.; Magiorkinis, E.; Paraskevis, D.; Ho, S.Y.; Shapiro, B.; Pybus, O.G.; Allain, J.P.; Hatzakis, A. The global spread of hepatitis C virus 1a and 1b: A phylodynamic and phylogeographic analysis. PLoS Med. 2009, 6, e1000198. [CrossRef] [PubMed]
85. Pybus, O.G.; Charleston, M.A.; Gupta, S.; Rambaut, A.; Holmes, E.C.; Harvey, P.H. The epidemic behavior of the hepatitis C virus. Science 2001, 292, 2323–2325. [CrossRef] [PubMed]
86. Klenerman, P.; Fleming, V.; Barnes, E. What are the prospects for controlling hepatitis C? PLoS Med. 2009, 6, e1000096. [CrossRef] [PubMed]
87. Simmonds, P. Genetic diversity and evolution of hepatitis C virus—15 years on. J. Gen. Virol. 2004, 85, 3173–3188. [CrossRef] [PubMed]
88. Brown, R.J.; Koutsoudakis, G.; Urbanowicz, R.A.; Mirza, D.; Ginkel, C.; Riebesehl, N.; Calland, N.; Albecka, A.; Price, L.; Hudson, N., et al. Analysis of serine codon conservation reveals diverse phenotypic constraints on hepatitis C virus glycoprotein evolution. J. Virol. 2014, 88, 667–678. [CrossRef] [PubMed]
89. Munshaw, S.; Bailey, J.R.; Liu, L.; Osburn, W.O.; Burke, K.P.; Cox, A.L.; Ray, S.C. Computational reconstruction of Bole1a, a representative synthetic hepatitis C virus subtype 1a genome. J. Virol. 2012, 86, 5915–5921. [CrossRef] [PubMed]
90. Burke, L.P.; Munshaw, S.; Osburn, W.O.; Levine, J.; Liu, L.; Sidney, J.; Sette, A.; Ray, S.C.; Cox, A.L. Immunogenicity and cross-reactivity of a representative ancestral sequence in hepatitis C virus infection. J. Immunol. 2012, 5177–5188. [CrossRef] [PubMed]
91. Salazar-Gonzalez, J.F.; Bailes, E.; Pham, K.T.; Salazar, M.G.; Guffey, M.B.; Keele, B.F.; Derdeyn, C.A.; Farmer, P.; Hunter, E.; Allen, S., et al. Deciphering human immunodeficiency virus type 1 transmission and early envelope diversification by single-genome amplification and sequencing. J. Virol. 2008, 82, 3952–3970. [CrossRef] [PubMed]
92. Wang, G.P.; Sherrill-Mix, S.A.; Chang, K.M.; Quince, C.; Bushman, F.D. Hepatitis C virus transmission bottlenecks analyzed by deep sequencing. J. Virol. 2010, 84, 6218–6228. [CrossRef] [PubMed]
93. Herring, B.L.; Tsui, R.; Peddada, L.; Busch, M.; Delwart, E.L. Wide range of quasispecies diversity during primary hepatitis C virus infection. J. Virol. 2005, 79, 4340–4346. [CrossRef] [PubMed]
94. Li, H.; Stoddard, M.B.; Wang, S.; Blair, L.M.; Giorgi, E.E.; Parrish, E.H.; Learn, G.H.; Hraber, P.; Goepfert, P.A.; Saag, M.S.; Denny, T.N., et al. Elucidation of hepatitis C virus transmission and early diversification by single genome sequencing. PLoS Pathog. 2012, 8, e1002880. [CrossRef] [PubMed]
95. Stoddard, M.B.; Li, H.; Wang, S.; Saeed, M.; Andrus, L.; Ding, W.; Jiang, X.; Learn, G.H.; von Schaewen, M.; Wen, J., et al. Identification, molecular cloning, and analysis of full-length hepatitis C virus transmitted/founder genotypes 1, 3, and 4. MBio 2015, 6, e02518-14. [CrossRef] [PubMed]
96. Mitchell, A.M.; Stone, A.E.; Cheng, L.; Ballinger, K.; Edwards, M.G.; Stoddard, M.; Li, H.; Golden-Mason, L.; Shaw, G.M.; Khetani, S., et al. Transmitted/founder hepatitis c viruses induce cell-type- and genotype-specific differences in innate signaling within the liver. MBio 2015, 6, e02510-14. [CrossRef] [PubMed]
97. Pond, S.L.; Frost, S.D.; Muse, S.V. HyPhy: Hypothesis testing using phylogenies. Bioinformatics 2005, 21, 676–679. [CrossRef] [PubMed]
98. Tamura, K.; Stecher, G.; Filipski, A.; Kumar, S. MEGA6: Molecular evolutionary genetics analysis version 6.0. Mol. Biol. Evol. 2013, 30, 2725–2729. [CrossRef] [PubMed]
99. Glaser, F.; Pupko, T.; Paz, I.; Bell, R.E.; Bechor-Shental, D.; Martz, E.; Ben-Tal, N. ConSurf: identification of functional regions in proteins by surface-mapping of phylogenetic information. Bioinformatics 2003, 19, 163–164. [CrossRef] [PubMed]
100. Brown, R.J.; Hudson, N.; Wilson, G.; Rehman, S.U.; Jabbari, S.; Hu, K.; Tarr, A.W.; Borrow, P.; Joyce, M.; Lewis, J., et al. Hepatitis C virus envelope glycoprotein fitness defines virus population composition following transmission to a new host. J. Virol. 2012, 86, 11956–11966. [CrossRef] [PubMed]
101. D’Arienzo, V.; Moreau, A.; D’Alteroche, L.; Gissot, V.; Blanchard, E.; Gaudy-Graffin, C.; Roch, E.; Dubois, F.; Giraudeau, B.; Plantier, J.C., et al. Sequence and functional analysis of the envelope glycoproteins of hepatitis C virus variants selectively transmitted to a new host. J. Virol. 2013, 87, 13609–13618. [CrossRef] [PubMed]
102. Honegger, J.R.; Kim, S.; Price, A.A.; Kohout, J.A.; McKnight, K.L.; Prasad, M.R.; Lemon, S.M.; Grakoui, A.; Walker, C.M. Loss of immune escape mutations during persistent HCV infection in pregnancy enhances replication of vertically transmitted viruses. Nat. Med. 2013, 19, 1529–1533. [CrossRef] [PubMed]
103. Gray, R.R.; Strickland, S.L.; Veras, N.M.; Goodenow, M.M.; Pybus, O.G.; Lemon, S.M.; Fried, M.W.; Nelson, D.R.; Salemi, M. Unexpected maintenance of hepatitis C viral diversity following liver transplantation. J. Virol. 2012, 86, 8432–8439. [CrossRef] [PubMed]
104. Fafi-Kremer, S.; Fofana, I.; Soulier, E.; Carolla, P.; Meuleman, P.; Leroux-Roels, G.; Patel, A.H.; Cosset, F.L.; Pessaux, P.; Doffoel, M., et al. Viral entry and escape from antibody-mediated neutralization influence hepatitis C virus reinfection in liver transplantation. J. Exp. Med. 2010, 207, 2019–2031. [CrossRef] [PubMed]
105. Ribeiro, R.M.; Li, H.; Wang, S.; Stoddard, M.B.; Learn, G.H.; Korber, B.T.; Bhattacharya, T.; Guedj, J.; Parrish, E.H.; Hahn, B.H., et al. Quantifying the diversification of hepatitis C virus (HCV) during primary infection: Estimates of the in vivo mutation rate. PLoS Pathog. 2012, 8, e1002881. [CrossRef] [PubMed]
106. Smith, J.A.; Aberle, J.H.; Fleming, V.M.; Ferenci, P.; Thomson, E.C.; Karayiannis, P.; McLean, A.R.; Holzmann, H.; Klenerman, P. Dynamic coinfection with multiple viral subtypes in acute hepatitis C. J. Infect. Dis. 2010, 202, 1770–1779. [CrossRef] [PubMed]
107. Edwards, V.C.; McClure, C.P.; Brown, R.J.; Thompson, E.; Irving, W.L.; Ball, J.K. Use of short tandem repeat fingerprinting to validate sample origins in hepatitis C virus molecular epidemiology studies. J. Gen. Virol. 2014, 95, 66–70. [CrossRef] [PubMed]
108. Irving, W.L.; Brown, R.J. Acute hepatitis C virus infection: A dynamic-and challenging-concept. J. Infect. Dis. 2010, 202, 1765–1767. [CrossRef] [PubMed]
109. Farci, P.; Shimoda, A.; Coiana, A.; Diaz, G.; Peddis, G.; Melpolder, J.C.; Strazzera, A.; Chien, D.Y.; Munoz, S.J.; Balestrieri, A., et al. The outcome of acute hepatitis C predicted by the evolution of the viral quasispecies. Science 2000, 288, 339–344. [CrossRef] [PubMed]
110. Ray, S.C.; Wang, Y.M.; Laeyendecker, O.; Ticehurst, J.R.; Villano, S.A.; Thomas, D.L. Acute hepatitis C virus structural gene sequences as predictors of persistent viremia: Hypervariable region 1 as a decoy. J. Virol. 1999, 73, 2938–2946. [PubMed]
111. Sheridan, I.; Pybus, O.G.; Holmes, E.C.; Klenerman, P. High-resolution phylogenetic analysis of hepatitis c virus adaptation and its relationship to disease progression. J. Virol. 2004, 78, 3447–3454. [CrossRef] [PubMed]
112. Bull, R.A.; Luciani, F.; McElroy, K.; Gaudieri, S.; Pham, S.T.; Chopra, A.; Cameron, B.; Maher, L.; Dore, G.J.; White, P.A., et al. Sequential bottlenecks drive viral evolution in early acute hepatitis C virus infection. PLoS Pathog. 2011, 7, e1002243. [CrossRef] [PubMed]
113. Callendret, B.; Bukh, J.; Eccleston, H.B.; Heksch, R.; Hasselschwert, D.L.; Purcell, R.H.; Hughes, A.L.; Walker, C.M. Transmission of clonal hepatitis C virus genomes reveals the dominant but transitory role of CD8(+) T cells in early viral evolution. J. Virol. 2011, 85, 11833–11845. [CrossRef] [PubMed]
114. Kuntzen, T.; Timm, J.; Berical, A.; Lewis-Ximenez, L.L.; Jones, A.; Nolan, B.; Schulze zur Wiesch, J.; Li, B.; Schneidewind, A.; Kim, A.Y., et al. Viral sequence evolution in acute hepatitis C virus infection. J. Virol. 2007, 81, 11658–11668. [CrossRef] [PubMed]
115. Bull, R.A.; Leung, P.; Gaudieri, S.; Deshpande, P.; Cameron, B.; Walker, M.; Chopra, A.; Lloyd, A.R.; Luciani, F. The transmitted/founder viruses rapidly escape from CD8+ T cell responses in acute hepatitis C infection. J. Virol. 2015, 89, 5478–5490. [CrossRef] [PubMed]
116. Dowd, K.A.; Netski, D.M.; Wang, X.H.; Cox, A.L.; Ray, S.C. Selection pressure from neutralizing antibodies drives sequence evolution during acute infection with hepatitis C virus. Gastroenterology 2009, 136, 2377–2386. [CrossRef] [PubMed]
117. Osburn, W.O.; Snider, A.E.; Wells, B.L.; Latanich, R.; Bailey, J.R.; Thomas, D.L.; Cox, A.L.; Ray, S.C. Clearance of hepatitis C infection is associated with the early appearance of broad neutralizing antibody responses. Hepatology 2014, 59, 2140–2151. [CrossRef] [PubMed]
118. Pestka, J.M.; Zeisel, M.B.; Blaser, E.; Schurmann, P.; Bartosch, B.; Cosset, F.L.; Patel, A.H.; Meisel, H.; Baumert, J.; Viazov, S., et al. Rapid induction of virus-neutralizing antibodies and viral clearance in a single-source outbreak of hepatitis C. Proc. Natl. Acad. Sci. USA 2007, 104, 6025–6030. [CrossRef] [PubMed]
119. Graw, F.; Balagopal, A.; Kandathil, A.J.; Ray, S.C.; Thomas, D.L.; Ribeiro, R.M.; Perelson, A.S. Inferring viral dynamics in chronically HCV infected patients from the spatial distribution of infected hepatocytes. PLoS Comput. Biol. 2014, 10, e1003934. [CrossRef] [PubMed]
120. Farci, P.; Wollenberg, K.; Diaz, G.; Engle, R.E.; Lai, M.E.; Klenerman, P.; Purcell, R.H.; Pybus, O.G.; Alter, H.J. Profibrogenic chemokines and viral evolution predict rapid progression of hepatitis C to cirrhosis. Proc. Natl. Acad. Sci. USA 2012, 109, 14562–14567. [CrossRef] [PubMed]
121. Farci, P.; Quinti, I.; Farci, S.; Alter, H.J.; Strazzera, R.; Palomba, E.; Coiana, A.; Cao, D.; Casadei, A.M.; Ledda, R., et al. Evolution of hepatitis C viral quasispecies and hepatic injury in perinatally infected children followed prospectively. Proc. Natl. Acad. Sci. USA 2006, 103, 8475–8480. [CrossRef] [PubMed]
122. Li, H.; McMahon, B.J.; McArdle, S.; Bruden, D.; Sullivan, D.G.; Shelton, D.; Deubner, H.; Gretch, D.R. Hepatitis C virus envelope glycoprotein co-evolutionary dynamics during chronic hepatitis C. Virology 2008, 375, 580–591. [CrossRef] [PubMed]
123. Brown, R.J.; Juttla, V.S.; Tarr, A.W.; Finnis, R.; Irving, W.L.; Hemsley, S.; Flower, D.R.; Borrow, P.; Ball, J.K. Evolutionary dynamics of hepatitis C virus envelope genes during chronic infection. J. Gen. Virol. 2005, 86, 1931–1942. [CrossRef] [PubMed]
124. Palmer, B.A.; Dimitrova, Z.; Skums, P.; Crosbie, O.; Kenny-Walsh, E.; Fanning, L.J. Analysis of the evolution and structure of a complex intrahost viral population in chronic hepatitis C virus mapped by ultradeep pyrosequencing. J. Virol. 2014, 88, 13709–13721. [CrossRef] [PubMed]
125. Ramachandran, S.; Campo, D.S.; Dimitrova, Z.E.; Xia, G.L.; Purdy, M.A.; Khudyakov, Y.E. Temporal variations in the hepatitis C virus intrahost population during chronic infection. J. Virol. 2011, 85, 6369–6380. [CrossRef] [PubMed]
126. Bailey, J.R.; Laskey, S.; Wasilewski, L.N.; Munshaw, S.; Fanning, L.J.; Kenny-Walsh, E.; Ray, S.C. Constraints on viral evolution during chronic hepatitis C virus infection arising from a common-source exposure. J. Virol. 2012, 86, 12582–12590. [CrossRef] [PubMed]
127. Logvinoff, C.; Major, M.E.; Oldach, D.; Heyward, S.; Talal, A.; Balfe, P.; Feinstone, S.M.; Alter, H.; Rice, C.M.; McKeating, J.A. Neutralizing antibody response during acute and chronic hepatitis C virus infection. Proc. Natl. Acad. Sci. USA 2004, 101, 10149–10154. [CrossRef] [PubMed]
128. Von Hahn, T.; Yoon, J.C.; Alter, H.; Rice, C.M.; Rehermann, B.; Balfe, P.; McKeating, J.A. Hepatitis C virus continuously escapes from neutralizing antibody and T-cell responses during chronic infection in vivo. Gastroenterology 2007, 132, 667–678. [CrossRef] [PubMed]
129. Irving, W.L.; Rupp, D.; McClure, C.P.; Than, L.M.; Titman, A.; Ball, J.K.; Steinmann, E.; Bartenschlager, R.; Pietschmann, T.; Brown, R.J. Development of a high-throughput pyrosequencing assay for monitoring temporal evolution and resistance associated variant emergence in the Hepatitis C virus protease coding-region. Antivir. Res. 2014, 110, 52–59. [CrossRef] [PubMed]
130. Fernandez, J.; Taylor, D.; Morhardt, D.R.; Mihalik, K.; Puig, M.; Rice, C.M.; Feinstone, S.M.; Major, M.E. Long-term persistence of infection in chimpanzees inoculated with an infectious hepatitis C virus clone is associated with a decrease in the viral amino acid substitution rate and low levels of heterogeneity. J. Virol. 2004, 78, 9782–9789. [CrossRef] [PubMed]
131. Meunier, J.C.; Russell, R.S.; Goossens, V.; Priem, S.; Walter, H.; Depla, E.; Union, A.; Faulk, K.N.; Bukh, J.; Emerson, S.U., et al. Isolation and characterization of broadly neutralizing human monoclonal antibodies to the e1 glycoprotein of hepatitis C virus. J. Virol. 2008, 82, 966–973. [CrossRef] [PubMed]
132. Keck, Z.Y.; Sung, V.M.; Perkins, S.; Rowe, J.; Paul, S.; Liang, T.J.; Lai, M.M.; Foung, S.K. Human monoclonal antibody to hepatitis C virus E1 glycoprotein that blocks virus attachment and viral infectivity. J. Virol. 2004, 78, 7257–7263. [CrossRef] [PubMed]
133. Leroux-Roels, G.; Depla, E.; Hulstaert, F.; Tobback, L.; Dincq, S.; Desmet, J.; Desombere, I.; Maertens, G. A candidate vaccine based on the hepatitis C E1 protein: Tolerability and immunogenicity in healthy volunteers. Vaccine 2004, 22, 3080–3086. [CrossRef] [PubMed]
134. Liu, R.; Rao, H.; Wang, J.; Xie, X.; Jiang, D.; Pan, X.; Zhao, P.; Zhang, H.; Wei, L. Determination of the human antibody response to the neutralization epitopes encompassing amino acids 313–327 and 432–443 of hepatitis C virus E1E2 glycoproteins. PLoS ONE 2013, 8, e66872. [CrossRef] [PubMed]
135. Farci, P.; Shimoda, A.; Wong, D.; Cabezon, T.; De Gioannis, D.; Strazzera, A.; Shimizu, Y.; Shapiro, M.; Alter, H.J.; Purcell, R.H. Prevention of hepatitis C virus infection in chimpanzees by hyperimmune serum against the hypervariable region 1 of the envelope 2 protein. Proc. Natl. Acad. Sci. USA 1996, 93, 15394–15399. [CrossRef] [PubMed]
136. Mondelli, M.U.; Cerino, A.; Segagni, L.; Meola, A.; Cividini, A.; Silini, E.; Nicosia, A. Hypervariable region 1 of hepatitis C virus: Immunological decoy or biologically relevant domain? Antivir. Res. 2001, 52, 153–159. [CrossRef]
137. Vieyres, G.; Dubuisson, J.; Patel, A.H. Characterization of antibody-mediated neutralization directed against the hypervariable region 1 of hepatitis C virus E2 glycoprotein. J. Gen. Virol. 2011, 92, 494–506. [CrossRef] [PubMed]
138. Sabo, M.C.; Luca, V.C.; Prentoe, J.; Hopcraft, S.E.; Blight, K.J.; Yi, M.; Lemon, S.M.; Ball, J.K.; Bukh, J.; Evans, M.J. Neutralizing monoclonal antibodies against hepatitis C virus E2 protein bind discontinuous epitopes and inhibit infection at a postattachment step. J. Virol. 2011, 85, 7005–7019. [CrossRef] [PubMed]
139. Hadlock, K.G.; Lanford, R.E.; Perkins, S.; Rowe, J.; Yang, Q.; Levy, S.; Pileri, P.; Abrignani, S.; Foung, S.K. Human monoclonal antibodies that inhibit binding of hepatitis C virus E2 protein to CD81 and recognize conserved conformational epitopes. J. Virol. 2000, 74, 10407–10416. [CrossRef] [PubMed]
140. Keck, Z.Y.; Li, T.K.; Xia, J.; Gal-Tanamy, M.; Olson, O.; Li, S.H.; Patel, A.H.; Ball, J.K.; Lemon, S.M.; Foung, S.K. Definition of a conserved immunodominant domain on hepatitis C virus E2 glycoprotein by neutralizing human monoclonal antibodies. J. Virol. 2008, 82, 6061–6066. [CrossRef] [PubMed]
141. Keck, Z.Y.; Xia, J.; Cai, Z.; Li, T.K.; Owsianka, A.M.; Patel, A.H.; Luo, G.; Foung, S.K. Immunogenic and functional organization of hepatitis C virus (HCV) glycoprotein E2 on infectious HCV virions. J. Virol. 2007, 81, 1043–1047. [CrossRef] [PubMed]
142. Keck, Z.Y.; Xia, J.; Wang, Y.; Wang, W.; Krey, T.; Prentoe, J.; Carlsen, T.; Li, A.Y.; Patel, A.H.; Lemon, S.M., et al. Human monoclonal antibodies to a novel cluster of conformational epitopes on HCV E2 with resistance to neutralization escape in a genotype 2a isolate. PLoS Pathog. 2012, 8, e1002653. [CrossRef] [PubMed]
143. Keck, Z.Y.; Saha, A.; Xia, J.; Wang, Y.; Lau, P.; Krey, T.; Rey, F.A.; Foung, S.K. Mapping a region of hepatitis C virus E2 that is responsible for escape from neutralizing antibodies and a core CD81-binding region that does not tolerate neutralization escape mutations. J. Virol. 2011, 85, 10451–10463. [CrossRef] [PubMed]
144. Habersetzer, F.; Fournillier, A.; Dubuisson, J.; Rosa, D.; Abrignani, S.; Wychowski, C.; Nakano, I.; Trepo, C.; Desgranges, C.; Inchauspe, G. Characterization of human monoclonal antibodies specific to the hepatitis C virus glycoprotein E2 with in vitro binding neutralization properties. Virology 1998, 249, 32–41. [CrossRef] [PubMed]
145. Law, M.; Maruyama, T.; Lewis, J.; Giang, E.; Tarr, A.W.; Stamataki, Z.; Gastaminza, P.; Chisari, F.V.; Jones, I.M.; Fox, R.I., et al. Broadly neutralizing antibodies protect against hepatitis C virus quasispecies challenge. Nat. Med. 2008, 14, 25–27. [CrossRef] [PubMed]
146. Johansson, D.X.; Voisset, C.; Tarr, A.W.; Aung, M.; Ball, J.K.; Dubuisson, J.; Persson, M.A. Human combinatorial libraries yield rare antibodies that broadly neutralize hepatitis C virus. Proc. Natl. Acad. Sci. USA 2007, 104, 16269–16274. [CrossRef] [PubMed]
147. Perotti, M.; Mancini, N.; Diotti, R.A.; Tarr, A.W.; Ball, J.K.; Owsianka, A.; Adair, R.; Patel, A.H.; Clementi, M.; Burioni, R. Identification of a broadly cross-reacting and neutralizing human monoclonal antibody directed against the hepatitis C virus E2 protein. J. Virol. 2008, 82, 1047–1052. [CrossRef] [PubMed]
148. Burioni, R.; Mancini, N.; Carletti, S.; Perotti, M.; Grieco, A.; Canducci, F.; Varaldo, P.E.; Clementi, M. Cross-reactive pseudovirus-neutralizing anti-envelope antibodies coexist with antibodies devoid of such activity in persistent hepatitis C virus infection. Virology 2004, 327, 242–248. [CrossRef] [PubMed]
149. Bugli, F.; Mancini, N.; Kang, C.Y.; Di Campli, C.; Grieco, A.; Manzin, A.; Gabrielli, A.; Gasbarrini, A.; Fadda, G.; Varaldo, P.E., et al. Mapping B-cell epitopes of hepatitis C virus E2 glycoprotein using human monoclonal antibodies from phage display libraries. J. Virol. 2001, 75, 9986–9990. [CrossRef] [PubMed]
150. Giang, E.; Dorner, M.; Prentoe, J.C.; Dreux, M.; Evans, M.J.; Bukh, J.; Rice, C.M.; Ploss, A.; Burton, D.R.; Law, M. Human broadly neutralizing antibodies to the envelope glycoprotein complex of hepatitis C virus. Proc. Natl. Acad. Sci. USA 2012, 109, 6205–6210. [CrossRef] [PubMed]
151. Ball, J.K.; Tarr, A.W.; McKeating, J.A. The past, present and future of neutralizing antibodies for hepatitis C virus. Antivir. Res. 2014, 105, 100–111. [CrossRef] [PubMed]
152. Edwards, V.C.; Tarr, A.W.; Urbanowicz, R.A.; Ball, J.K. The role of neutralizing antibodies in hepatitis C virus infection. J. Gen. Virol. 2012, 93, 1–19. [CrossRef] [PubMed]
153. Bassett, S.E.; Thomas, D.L.; Brasky, K.M.; Lanford, R.E. Viral persistence, antibody to E1 and E2, and hypervariable region 1 sequence stability in hepatitis C virus-inoculated chimpanzees. J. Virol. 1999, 73, 1118–1126. [PubMed]
154. Osburn, W.O.; Fisher, B.E.; Dowd, K.A.; Urban, G.; Liu, L.; Ray, S.C.; Thomas, D.L.; Cox, A.L. Spontaneous control of primary hepatitis C virus infection and immunity against persistent reinfection. Gastroenterology 2010, 138, 315–324. [CrossRef] [PubMed]
155. Lavillette, D.; Morice, Y.; Germanidis, G.; Donot, P.; Soulier, A.; Pagkalos, E.; Sakellariou, G.; Intrator, L.; Bartosch, B.; Pawlotsky, J.M., et al. Human serum facilitates hepatitis C virus infection, and neutralizing responses inversely correlate with viral replication kinetics at the acute phase of hepatitis C virus infection. J. Virol. 2005, 79, 6023–6034. [CrossRef] [PubMed]
156. Tarr, A.W.; Urbanowicz, R.A.; Hamed, M.R.; Albecka, A.; McClure, C.P.; Brown, R.J.; Irving, W.L.; Dubuisson, J.; Ball, J.K. Hepatitis C patient-derived glycoproteins exhibit marked differences in susceptibility to serum neutralizing antibodies: Genetic subtype defines antigenic but not neutralization serotype. J. Virol. 2011, 85, 4246–4257. [CrossRef] [PubMed]
157. Meunier, J.C.; Engle, R.E.; Faulk, K.; Zhao, M.; Bartosch, B.; Alter, H.; Emerson, S.U.; Cosset, F.L.; Purcell, R.H.; Bukh, J. Evidence for cross-genotype neutralization of hepatitis C virus pseudo-particles and enhancement of infectivity by apolipoprotein C1. Proc. Natl. Acad. Sci. USA 2005, 102, 4560–4565. [CrossRef] [PubMed]
158. Clayton, R.F.; Owsianka, A.; Aitken, J.; Graham, S.; Bhella, D.; Patel, A.H. Analysis of antigenicity and topology of E2 glycoprotein present on recombinant hepatitis C virus-like particles. J. Virol. 2002, 76, 7672–7682. [CrossRef] [PubMed]
159. Flint, M.; Maidens, C.; Loomis-Price, L.D.; Shotton, C.; Dubuisson, J.; Monk, P.; Higginbottom, A.; Levy, S.; McKeating, J.A. Characterization of hepatitis C virus E2 glycoprotein interaction with a putative cellular receptor, CD81. J. Virol. 1999, 73, 6235–6244. [PubMed]
160. Owsianka, A.; Tarr, A.W.; Juttla, V.S.; Lavillette, D.; Bartosch, B.; Cosset, F.L.; Ball, J.K.; Patel, A.H. Monoclonal antibody AP33 defines a broadly neutralizing epitope on the hepatitis C virus E2 envelope glycoprotein. J. Virol. 2005, 79, 11095–11104. [CrossRef] [PubMed]
161. Gal-Tanamy, M.; Keck, Z.Y.; Yi, M.; McKeating, J.A.; Patel, A.H.; Foung, S.K.; Lemon, S.M. In vitro selection of a neutralization-resistant hepatitis C virus escape mutant. Proc. Natl. Acad. Sci. USA 2008, 105, 19450–19455. [CrossRef] [PubMed]
162. Wong, J.A.; Bhat, R.; Hockman, D.; Logan, M.; Chen, C.; Levin, A.; Frey, S.E.; Belshe, R.B.; Tyrrell, D.L.; Law, J.L., et al. Recombinant hepatitis C virus envelope glycoprotein vaccine elicits antibodies targeting multiple epitopes on the envelope glycoproteins associated with broad cross-neutralization. J. Virol. 2014, 88, 14278–14288. [CrossRef] [PubMed]
163. Tarr, A.W.; Lafaye, P.; Meredith, L.; Damier-Piolle, L.; Urbanowicz, R.A.; Meola, A.; Jestin, J.L.; Brown, R.J.; McKeating, J.A.; Rey, F.A., et al. An alpaca nanobody inhibits hepatitis C virus entry and cell-to-cell transmission. Hepatology 2013, 58, 932–939. [CrossRef] [PubMed]
164. Chmielewska, A.M.; Naddeo, M.; Capone, S.; Ammendola, V.; Hu, K.; Meredith, L.; Verhoye, L.; Rychlowska, M.; Rappuoli, R.; Ulmer, J.B., et al. Combined adenovirus vector and hepatitis C virus envelope protein prime-boost regimen elicits T cell and neutralizing antibody immune responses. J. Virol. 2014, 88, 5502–5510. [CrossRef] [PubMed]
165. Stamataki, Z.; Coates, S.; Evans, M.J.; Wininger, M.; Crawford, K.; Dong, C.; Fong, Y.L.; Chien, D.; Abrignani, S.; Balfe, P., et al. Hepatitis C virus envelope glycoprotein immunization of rodents elicits cross-reactive neutralizing antibodies. Vaccine 2007, 25, 7773–7784. [CrossRef] [PubMed]
166. Stamataki, Z.; Coates, S.; Abrignani, S.; Houghton, M.; McKeating, J.A. Immunization of human volunteers with hepatitis C virus envelope glycoproteins elicits antibodies that cross-neutralize heterologous virus strains. J. Infect. Dis. 2011, 204, 811–813. [CrossRef] [PubMed]
167. Verstrepen, B.E.; Depla, E.; Rollier, C.S.; Mares, G.; Drexhage, J.A.; Priem, S.; Verschoor, E.J.; Koopman, G.; Granier, C.; Dreux, M., et al. Clearance of genotype 1b hepatitis C virus in chimpanzees in the presence of vaccine-induced E1-neutralizing antibodies. J. Infect. Dis. 2011, 204, 837–844. [CrossRef] [PubMed]
168. Ruwona, T.B.; Giang, E.; Nieusma, T.; Law, M. Fine mapping of murine antibody responses to immunization with a novel soluble form of hepatitis C virus envelope glycoprotein complex. J. Virol. 2014, 88, 10459–10471. [CrossRef] [PubMed]
169. Tarr, A.W.; Owsianka, A.M.; Timms, J.M.; McClure, C.P.; Brown, R.J.; Hickling, T.P.; Pietschmann, T.; Bartenschlager, R.; Patel, A.H.; Ball, J.K. Characterization of the hepatitis C virus E2 epitope defined by the broadly neutralizing monoclonal antibody AP33. Hepatology 2006, 43, 592–601. [CrossRef] [PubMed]
170. Helle, F.; Goffard, A.; Morel, V.; Duverlie, G.; McKeating, J.; Keck, Z.Y.; Foung, S.; Penin, F.; Dubuisson, J.; Voisset, C. The neutralizing activity of anti-hepatitis C virus antibodies is modulated by specific glycans on the E2 envelope protein. J. Virol. 2007, 81, 8101–8111. [CrossRef] [PubMed]
171. Pantua, H.; Diao, J.; Ultsch, M.; Hazen, M.; Mathieu, M.; McCutcheon, K.; Takeda, K.; Date, S.; Cheung, T.K.; Phung, Q., et al. Glycan shifting on hepatitis C virus (HCV) E2 glycoprotein is a mechanism for escape from broadly neutralizing antibodies. J. Mol. Biol. 2013, 425, 1899–1914. [CrossRef] [PubMed]
172. Anjum, S.; Wahid, A.; Afzal, M.S.; Albecka, A.; Alsaleh, K.; Ahmad, T.; Baumert, T.F.; Wychowski, C.; Qadri, I.; Penin, F., et al. Additional glycosylation within a specific hypervariable region of subtype 3a of hepatitis C virus protects against virus neutralization. J. Infect. Dis. 2013, 208, 1888–1897. [CrossRef] [PubMed]
173. Helle, F.; Wychowski, C.; Vu-Dac, N.; Gustafson, K.R.; Voisset, C.; Dubuisson, J. Cyanovirin-N inhibits hepatitis C virus entry by binding to envelope protein glycans. J. Biol. Chem. 2006, 281, 25177–25183. [CrossRef] [PubMed]
174. Kachko, A.; Loesgen, S.; Shahzad-Ul-Hussan, S.; Tan, W.; Zubkova, I.; Takeda, K.; Wells, F.; Rubin, S.; Bewley, C.A.; Major, M.E. Inhibition of hepatitis C virus by the cyanobacterial protein Microcystis viridis lectin: Mechanistic differences between the high-mannose specific lectins MVL, CV-N, and GNA. Mol. Pharm. 2013, 10, 4590–4602. [CrossRef] [PubMed]
175. Hamed, M.R.; Brown, R.J.; Zothner, C.; Urbanowicz, R.A.; Mason, C.P.; Krarup, A.; McClure, C.P.; Irving, W.L.; Ball, J.K.; Harris, M., et al. Recombinant human L-ficolin directly neutralizes hepatitis C virus entry. J. Innate Immun. 2014, 6, 676–684. [CrossRef] [PubMed]
176. Zhao, Y.; Ren, Y.; Zhang, X.; Zhao, P.; Tao, W.; Zhong, J.; Li, Q.; Zhang, X.L. Ficolin-2 inhibits hepatitis C virus infection, whereas apolipoprotein E3 mediates viral immune escape. J. Immunol. 2014, 193, 783–796. [CrossRef] [PubMed]
177. Dao Thi, V.L.; Granier, C.; Zeisel, M.B.; Guerin, M.; Mancip, J.; Granio, O.; Penin, F.; Lavillette, D.; Bartenschlager, R.; Baumert, T.F., et al. Characterization of hepatitis C virus particle subpopulations reveals multiple usage of the scavenger receptor BI for entry steps. J. Biol. Chem. 2012, 287, 31242–31257. [CrossRef] [PubMed]
178. Jiang, J.; Cun, W.; Wu, X.; Shi, Q.; Tang, H.; Luo, G. Hepatitis C virus attachment mediated by apolipoprotein E binding to cell surface heparan sulfate. J. Virol. 2012, 86, 7256–7267. [CrossRef] [PubMed]
179. Dreux, M.; Boson, B.; Ricard-Blum, S.; Molle, J.; Lavillette, D.; Bartosch, B.; Pecheur, E.I.; Cosset, F.L. The exchangeable apolipoprotein ApoC-I promotes membrane fusion of hepatitis C virus. J. Biol. Chem. 2007, 282, 32357–32369. [CrossRef] [PubMed]
180. Voisset, C.; Op de Beeck, A.; Horellou, P.; Dreux, M.; Gustot, T.; Duverlie, G.; Cosset, F.L.; Vu-Dac, N.; Dubuisson, J. High-density lipoproteins reduce the neutralizing effect of hepatitis C virus (HCV)-infected patient antibodies by promoting HCV entry. J. Gen. Virol. 2006, 87, 2577–2581. [CrossRef] [PubMed]
181. Dreux, M.; Pietschmann, T.; Granier, C.; Voisset, C.; Ricard-Blum, S.; Mangeot, P.E.; Keck, Z.; Foung, S.; Vu-Dac, N.; Dubuisson, J., et al. High density lipoprotein inhibits hepatitis C virus-neutralizing antibodies by stimulating cell entry via activation of the scavenger receptor BI. J. Biol. Chem. 2006, 281, 18285–18295. [CrossRef] [PubMed]
182. Brimacombe, C.L.; Grove, J.; Meredith, L.W.; Hu, K.; Syder, A.J.; Flores, M.V.; Timpe, J.M.; Krieger, S.E.; Baumert, T.F.; Tellinghuisen, T.L., et al. Neutralizing antibody-resistant hepatitis C virus cell-to-cell transmission. J. Virol. 2011, 85, 596–605. [CrossRef] [PubMed]
183. Witteveldt, J.; Evans, M.J.; Bitzegeio, J.; Koutsoudakis, G.; Owsianka, A.M.; Angus, A.G.; Keck, Z.Y.; Foung, S.K.; Pietschmann, T.; Rice, C.M., et al. CD81 is dispensable for hepatitis C virus cell-to-cell transmission in hepatoma cells. J. Gen. Virol. 2009, 90, 48–58. [CrossRef] [PubMed]
184. Timpe, J.M.; Stamataki, Z.; Jennings, A.; Hu, K.; Farquhar, M.J.; Harris, H.J.; Schwarz, A.; Desombere, I.; Roels, G.L.; Balfe, P., et al. Hepatitis C virus cell-cell transmission in hepatoma cells in the presence of neutralizing antibodies. Hepatology 2008, 47, 17-24. [CrossRef] [PubMed]
185. Meredith, L.W.; Harris, H.J.; Wilson, G.K.; Fletcher, N.F.; Balfe, P.; McKeating, J.A. Early infection events highlight the limited transmissibility of hepatitis C virus in vitro. J. Hepatol. 2013, 58, 1074–1080. [CrossRef] [PubMed]
186. Hueging, K.; Doepke, M.; Vieyres, G.; Bankwitz, D.; Frentzen, A.; Doerrbecker, J.; Gumz, F.; Haid, S.; Wolk, B.; Kaderali, L., et al. 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. J. Virol. 2014, 88, 1433–1446. [CrossRef] [PubMed]
187. Fofana, I.; Xiao, F.; Thumann, C.; Turek, M.; Zona, L.; Tawar, R.G.; Grunert, F.; Thompson, J.; Zeisel, M.B.; Baumert, T.F. A novel monoclonal anti-CD81 antibody produced by genetic immunization efficiently inhibits Hepatitis C virus cell-cell transmission. PLoS ONE 2013, 8, e64221. [CrossRef] [PubMed]
188. Meuleman, P.; Catanese, M.T.; Verhoye, L.; Desombere, I.; Farhoudi, A.; Jones, C.T.; Sheahan, T.; Grzyb, K.; Cortese, R.; Rice, C.M., et al. 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 2012, 55, 364–372. [CrossRef] [PubMed]
189. Xiao, F.; Fofana, I.; Heydmann, L.; Barth, H.; Soulier, E.; Habersetzer, F.; Doffoel, M.; Bukh, J.; Patel, A.H.; Zeisel, M.B., et al. Hepatitis C virus cell-cell transmission and resistance to direct-acting antiviral agents. PLoS Pathog. 2014, 10, e1004128. [CrossRef] [PubMed]
190. Deng, L.; Zhong, L.; Struble, E.; Duan, H.; Ma, L.; Harman, C.; Yan, H.; Virata-Theimer, M.L.; Zhao, Z.; Feinstone, S., et al. Structural evidence for a bifurcated mode of action in the antibody-mediated neutralization of hepatitis C virus. Proc. Natl. Acad. Sci. USA 2013, 110, 7418–7422. [CrossRef] [PubMed]
191. Zhang, P.; Zhong, L.; Struble, E.B.; Watanabe, H.; Kachko, A.; Mihalik, K.; Virata-Theimer, M.L.; Alter, H.J.; Feinstone, S.; Major, M. Depletion of interfering antibodies in chronic hepatitis C patients and vaccinated chimpanzees reveals broad cross-genotype neutralizing activity. Proc. Natl. Acad. Sci. USA 2009, 106, 7537–7541. [CrossRef] [PubMed]
192. Meyer, K.; Banerjee, A.; Frey, S.E.; Belshe, R.B.; Ray, R. A weak neutralizing antibody response to hepatitis C virus envelope glycoprotein enhances virus infection. PLoS ONE 2011, 6, e23699. [CrossRef] [PubMed]
193. Meyer, K.; Ait-Goughoulte, M.; Keck, Z.Y.; Foung, S.; Ray, R. Antibody-dependent enhancement of hepatitis C virus infection. J. Virol. 2008, 82, 2140–2149. [CrossRef] [PubMed]
194. Keck, Z.; Wang, W.; Wang, Y.; Lau, P.; Carlsen, T.H.; Prentoe, J.; Xia, J.; Patel, A.H.; Bukh, J.; Foung, S.K. Cooperativity in virus neutralization by human monoclonal antibodies to two adjacent regions located at the amino terminus of hepatitis C virus E2 glycoprotein. J. Virol. 2013, 87, 37–51. [CrossRef] [PubMed]
195. Zhang, P.; Wu, C.G.; Mihalik, K.; Virata-Theimer, M.L.; Yu, M.Y.; Alter, H.J.; Feinstone, S.M. Hepatitis C virus epitope-specific neutralizing antibodies in Igs prepared from human plasma. Proc. Natl. Acad. Sci. USA 2007, 104, 8449–8454. [CrossRef] [PubMed]
196. Deng, L.; Ma, L.; Virata-Theimer, M.L.; Zhong, L.; Yan, H.; Zhao, Z.; Struble, E.; Feinstone, S.; Alter, H.; Zhang, P. Discrete conformations of epitope II on the hepatitis C virus E2 protein for antibody-mediated neutralization and nonneutralization. Proc. Natl. Acad. Sci. USA 2014, 111, 10690–10695. [CrossRef] [PubMed]
197. Morel, A.; Passot, C.; Arnoult, C.; Dumans, A.; Beaumont, E.; Gouilleux-Gruart, V.; Roingeard, P.; Blanchard, E. The neonatal Fc receptor does not modulate hepatitis C virus neutralization. J. Gen. Virol. 2015, 96, 1062–1066. [CrossRef] [PubMed]
198. Evans, M.J.; von Hahn, T.; Tscherne, D.M.; Syder, A.J.; Panis, M.; Wolk, B.; Hatziioannou, T.; McKeating, J.A.; Bieniasz, P.D.; Rice, C.M. Claudin-1 is a hepatitis C virus co-receptor required for a late step in entry. Nature 2007, 446, 801–805. [CrossRef] [PubMed]
199. Ploss, A.; Evans, M.J.; Gaysinskaya, V.A.; Panis, M.; You, H.; de Jong, Y.P.; Rice, C.M. Human occludin is a hepatitis C virus entry factor required for infection of mouse cells. Nature 2009, 457, 882–886. [CrossRef] [PubMed]
200. Barth, H.; Schafer, C.; Adah, M.I.; Zhang, F.; Linhardt, R.J.; Toyoda, H.; Kinoshita-Toyoda, A.; Toida, T.; van Kuppevelt, T.H.; Depla, E., et al. Cellular binding of hepatitis C virus envelope glycoprotein E2 requires cell surface heparan sulfate. J. Biol. Chem. 2003, 278, 41003–41012. [CrossRef] [PubMed]
201. Koutsoudakis, G.; Kaul, A.; Steinmann, E.; Kallis, S.; Lohmann, V.; Pietschmann, T.; Bartenschlager, R. Characterization of the early steps of hepatitis C virus infection by using luciferase reporter viruses. J. Virol. 2006, 80, 5308–5320. [CrossRef] [PubMed]
202. Agnello, V.; Abel, G.; Elfahal, M.; Knight, G.B.; Zhang, Q.X. Hepatitis C virus and other flaviviridae viruses enter cells via low density lipoprotein receptor. Proc. Natl. Acad. Sci. USA 1999, 96, 12766–12771. [CrossRef] [PubMed]
203. Lupberger, J.; Zeisel, M.B.; Xiao, F.; Thumann, C.; Fofana, I.; Zona, L.; Davis, C.; Mee, C.J.; Turek, M.; Gorke, S., et al. EGFR and EphA2 are host factors for hepatitis C virus entry and possible targets for antiviral therapy. Nat. Med. 2011, 17, 589–595. [CrossRef] [PubMed]
204. Sainz, B., Jr.; Barretto, N.; Martin, D.N.; Hiraga, N.; Imamura, M.; Hussain, S.; Marsh, K.A.; Yu, X.; Chayama, K.; Alrefai, W.A., et al. Identification of the Niemann-Pick C1-like 1 cholesterol absorption receptor as a new hepatitis C virus entry factor. Nat. Med. 2012, 18, 281–285. [CrossRef] [PubMed]
205. Zona, L.; Lupberger, J.; Sidahmed-Adrar, N.; Thumann, C.; Harris, H.J.; Barnes, A.; Florentin, J.; Tawar, R.G.; Xiao, F.; Turek, M., et al. HRas signal transduction promotes hepatitis C virus cell entry by triggering assembly of the host tetraspanin receptor complex. Cell Host Microbe 2013, 13, 302–313. [CrossRef] [PubMed]
206. Martin, D.N.; Uprichard, L. Identification of transferrin receptor 1 as a hepatitis C virus entry factor. Proc. Natl. Acad. Sci. USA 2013, 110, 10777–10782. [CrossRef] [PubMed]
207. Wu, X.; Lee, E.M.; Hammack, C.; Robotham, J.M.; Basu, M.; Lang, J.; Brinton, M.A.; Tang, H. Cell death-inducing DFFA-like effector b is required for hepatitis C virus entry into hepatocytes. J. Virol. 2014, 88, 8433–8444. [CrossRef] [PubMed]
208. Li, Q.; Zhang, Y.Y.; Chiu, S.; Hu, Z.; Lan, K.H.; Cha, H.; Sodroski, C.; Zhang, F.; Hsu, C.S.; Thomas, E., et al. Integrative functional genomics of hepatitis C virus infection identifies host dependencies in complete viral replication cycle. PLoS Pathog. 2014, 10, e1004163. [CrossRef] [PubMed]
209. Andre, P.; Komurian-Pradel, F.; Deforges, S.; Perret, M.; Berland, J.L.; Sodoyer, M.; Pol, S.; Brechot, C.; Paranhos-Baccala, G.; Lotteau, V. Characterization of low- and very-low-density hepatitis C virus RNA-containing particles. J. Virol. 2002, 76, 6919–6928. [CrossRef] [PubMed]
210. Nielsen, S.U.; Bassendine, M.F.; Burt, A.D.; Martin, C.; Pumeechockchai, W.; Toms, G.L. Association between hepatitis C virus and very-low-density lipoprotein (VLDL)/LDL analyzed in iodixanol density gradients. J. Virol. 2006, 80, 2418–2428. [CrossRef] [PubMed]
211. Thomssen, R.; Bonk, S.; Propfe, C.; Heermann, K.H.; Kochel, H.G.; Uy, A. Association of hepatitis C virus in human sera with beta-lipoprotein. Med. Microbiol. Immunol. 1992, 181, 293–300. [CrossRef] [PubMed]
212. Merz, A.; Long, G.; Hiet, M.S.; Brugger, B.; Chlanda, P.; Andre, P.; Wieland, F.; Krijnse-Locker, J.; Bartenschlager, R. Biochemical and morphological properties of hepatitis C virus particles and determination of their lipidome. J. Biol. Chem. 2011, 286, 3018–3032. [CrossRef] [PubMed]
213. Owen, D.M.; Huang, H.; Ye, J.; Gale, M., Jr. Apolipoprotein E on hepatitis C virion facilitates infection through interaction with low-density lipoprotein receptor. Virology 2009, 394, 99–108. [CrossRef] [PubMed]
214. Hishiki, T.; Shimizu, Y.; Tobita, R.; Sugiyama, K.; Ogawa, K.; Funami, K.; Ohsaki, Y.; Fujimoto, T.; Takaku, H.; Wakita, T., et al. Infectivity of hepatitis C virus is influenced by association with apolipoprotein E isoforms. J. Virol. 2010, 84, 12048–12057. [CrossRef] [PubMed]
215. Maillard, P.; Huby, T.; Andreo, U.; Moreau, M.; Chapman, J.; Budkowska, A. The interaction of natural hepatitis C virus with human scavenger receptor SR-BI/Cla1 is mediated by ApoB-containing lipoproteins. FASEB J. 2006, 20, 735–737. [CrossRef] [PubMed]
216. Chang, K.S.; Jiang, J.; Cai, Z.; Luo, G. Human apolipoprotein e is required for infectivity and production of hepatitis C virus in cell culture. J. Virol. 2007, 81, 13783–13793. [CrossRef] [PubMed]
217. Gottwein, J.M.; Scheel, T.K.; Jensen, T.B.; Lademann, J.B.; Prentoe, J.C.; Knudsen, M.L.; Hoegh, A.M.; Bukh, J. Development and characterization of hepatitis C virus genotype 1–7 cell culture systems: Role of CD81 and scavenger receptor class B type I and effect of antiviral drugs. Hepatology 2009, 49, 364–377. [CrossRef] [PubMed]
218. Zheng, A.; Yuan, F.; Li, Y.; Zhu, F.; Hou, P.; Li, J.; Song, X.; Ding, M.; Deng, H. Claudin-6 and claudin-9 function as additional coreceptors for hepatitis C virus. J. Virol. 2007, 81, 12465–12471. [CrossRef] [PubMed]
219. Meertens, L.; Bertaux, C.; Cukierman, L.; Cormier, E.; Lavillette, D.; Cosset, F.L.; Dragic, T. The tight junction proteins claudin-1, -6, and -9 are entry cofactors for hepatitis C virus. J. Virol. 2008, 82, 3555–3560. [CrossRef] [PubMed]
220. Haid, S.; Grethe, C.; Dill, M.T.; Heim, M.; Kaderali, L.; Pietschmann, T. Isolate-dependent use of claudins for cell entry by hepatitis C virus. Hepatology 2014, 59, 24–34. [CrossRef] [PubMed]
221. Hopcraft, S.E.; Evans, M.J. Selection of a hepatitis C virus with altered entry factor requirements reveals a genetic interaction between the E1 glycoprotein and claudins. Hepatology 2015. [CrossRef] [PubMed]
222. Sourisseau, M.; Michta, M.L.; Zony, C.; Israelow, B.; Hopcraft, S.E.; Narbus, C.M.; Parra Martin, A.; Evans, M.J. Temporal analysis of hepatitis C virus cell entry with occludin directed blocking antibodies. PLoS Pathog. 2013, 9, e1003244. [CrossRef] [PubMed]
223. Zhong, J.; Gastaminza, P.; Chung, J.; Stamataki, Z.; Isogawa, M.; Cheng, G.; McKeating, J.A.; Chisari, F.V. Persistent hepatitis C virus infection in vitro: Coevolution of virus and host. J. Virol. 2006, 80, 11082–11093. [CrossRef] [PubMed]
224. Tao, W.; Xu, C.; Ding, Q.; Li, R.; Xiang, Y.; Chung, J.; Zhong, J. A single point mutation in E2 enhances hepatitis C virus infectivity and alters lipoprotein association of viral particles. Virology 2009, 395, 67–76. [CrossRef] [PubMed]
225. McCaffrey, K.; Gouklani, H.; Boo, I.; Poumbourios, P.; Drummer, H.E. The variable regions of hepatitis C virus glycoprotein E2 have an essential structural role in glycoprotein assembly and virion infectivity. J. Gen. Virol. 2011, 92, 112–121. [CrossRef] [PubMed]
226. Forns, X.; Thimme, R.; Govindarajan, S.; Emerson, S.U.; Purcell, R.H.; Chisari, F.V.; Bukh, J. Hepatitis C virus lacking the hypervariable region 1 of the second envelope protein is infectious and causes acute resolving or persistent infection in chimpanzees. Proc. Natl. Acad. Sci. USA 2000, 97, 13318–13323. [CrossRef] [PubMed]
227. Prentoe, J.; Serre, S.B.; Ramirez, S.; Nicosia, A.; Gottwein, J.M.; Bukh, J. Hypervariable region 1 deletion and required adaptive envelope mutations confer decreased dependency on scavenger receptor class B type I and low-density lipoprotein receptor for hepatitis C virus. J. Virol. 2014, 88, 1725–1739. [CrossRef] [PubMed]
228. Prentoe, J.; Jensen, T.B.; Meuleman, P.; Serre, S.B.; Scheel, T.K.; Leroux-Roels, G.; Gottwein, J.M.; Bukh, J. Hypervariable region 1 differentially impacts viability of hepatitis C virus strains of genotypes 1 to 6 and impairs virus neutralization. J. Virol. 2011, 85, 2224–2234. [CrossRef] [PubMed]
229. Vercauteren, K.; de Jong, Y.P.; Meuleman, P. HCV animal models and liver disease. J. Hepatol. 2014, 61 (Suppl. S1), S26–S33. [CrossRef] [PubMed]
230. Flint, M.; von Hahn, T.; Zhang, J.; Farquhar, M.; Jones, C.T.; Balfe, P.; Rice, C.M.; McKeating, J.A. Diverse CD81 proteins support hepatitis C virus infection. J. Virol. 2006, 80, 11331–11342. [CrossRef] [PubMed]
231. Michta, M.L.; Hopcraft, S.E.; Narbus, C.M.; Kratovac, Z.; Israelow, B.; Sourisseau, M.; Evans, M.J. Species-specific regions of occludin required by hepatitis C virus for cell entry. J. Virol. 2010, 84, 11696–11708. [CrossRef] [PubMed]
232. Bitzegeio, J.; Bankwitz, D.; Hueging, K.; Haid, S.; Brohm, C.; Zeisel, M.B.; Herrmann, E.; Iken, M.; Ott, M.; Baumert, T.F., et al. Adaptation of hepatitis C virus to mouse CD81 permits infection of mouse cells in the absence of human entry factors. PLoS Pathog. 2010, 6, e1000978. [CrossRef] [PubMed]
233. Sourisseau, M.; Goldman, O.; He, W.; Gori, J.L.; Kiem, H.P.; Gouon-Evans, V.; Evans, M.J. Hepatic cells derived from induced pluripotent stem cells of pigtail macaques support hepatitis C virus infection. Gastroenterology 2013, 145, 966–969. [CrossRef] [PubMed]
234. Appel, N.; Zayas, M.; Miller, S.; Krijnse-Locker, J.; Schaller, T.; Friebe, P.; Kallis, S.; Engel, U.; Bartenschlager, R. Essential role of domain III of nonstructural protein 5A for hepatitis C virus infectious particle assembly. PLoS Pathog. 2008, 4, e1000035. [CrossRef] [PubMed]
235. Jiang, J.; Luo, G. Cell culture-adaptive mutations promote viral protein-protein interactions and morphogenesis of infectious hepatitis C virus. J. Virol. 2012, 86, 8987–8997. [CrossRef] [PubMed]
236. Jones, C.T.; Murray, C.L.; Eastman, D.K.; Tassello, J.; Rice, C.M. Hepatitis C virus p7 and NS2 proteins are essential for production of infectious virus. J. Virol. 2007, 81, 8374–8383. [CrossRef] [PubMed]
237. Jones, D.M.; Patel, A.H.; Targett-Adams, P.; McLauchlan, J. The hepatitis C virus NS4B protein can trans-complement viral RNA replication and modulates production of infectious virus. J. Virol. 2009, 83, 2163–2177. [CrossRef] [PubMed]
238. Ma, Y.; Yates, J.; Liang, Y.; Lemon, S.M.; Yi, M. NS3 helicase domains involved in infectious intracellular hepatitis C virus particle assembly. J. Virol. 2008, 82, 7624–7639. [CrossRef] [PubMed]
239. Phan, T.; Beran, R.K.; Peters, C.; Lorenz, I.C.; Lindenbach, B.D. Hepatitis C virus NS2 protein contributes to virus particle assembly via opposing epistatic interactions with the E1-E2 glycoprotein and NS3-NS4A enzyme complexes. J. Virol. 2009, 83, 8379–8395. [CrossRef] [PubMed]
240. Steinmann, E.; Penin, F.; Kallis, S.; Patel, A.H.; Bartenschlager, R.; Pietschmann, T. Hepatitis C virus p7 protein is crucial for assembly and release of infectious virions. PLoS Pathog. 2007, 3, e103. [CrossRef] [PubMed]
241. Yi, M.; Ma, Y.; Yates, J.; Lemon, S.M. Compensatory mutations in E1, p7, NS2, and NS3 enhance yields of cell culture-infectious intergenotypic chimeric hepatitis C virus. J. Virol. 2007, 81, 629–638. [CrossRef] [PubMed]
242. Gastaminza, P.; Cheng, G.; Wieland, S.; Zhong, J.; Liao, W.; Chisari, F.V. Cellular determinants of hepatitis C virus assembly, maturation, degradation, and secretion. J. Virol. 2008, 82, 2120–2129. [CrossRef] [PubMed]
243. Huang, H.; Sun, F.; Owen, D.M.; Li, W.; Chen, Y.; Gale, M., Jr.; Ye, J. Hepatitis C virus production by human hepatocytes dependent on assembly and secretion of very low-density lipoproteins. Proc. Natl. Acad. Sci. USA 2007, 104, 5848–5853. [CrossRef] [PubMed]
244. Jiang, J.; Luo, G. Apolipoprotein E but not B is required for the formation of infectious hepatitis C virus particles. J. Virol. 2009, 83, 12680–12691. [CrossRef] [PubMed]
245. Da Costa, D.; Turek, M.; Felmlee, D.J.; Girardi, E.; Pfeffer, S.; Long, G.; Bartenschlager, R.; Zeisel, M.B.; Baumert, T.F. Reconstitution of the entire hepatitis C virus life cycle in nonhepatic cells. J. Virol. 2012, 86, 11919–11925. [CrossRef] [PubMed]
246. Fukuhara, T.; Wada, M.; Nakamura, S.; Ono, C.; Shiokawa, M.; Yamamoto, S.; Motomura, T.; Okamoto, T.; Okuzaki, D.; Yamamoto, M., et al. Amphipathic alpha-helices in apolipoproteins are crucial to the formation of infectious hepatitis C virus particles. PLoS Pathog. 2014, 10, e1004534. [CrossRef] [PubMed]
247. Maurin, G.; Fresquet, J.; Granio, O.; Wychowski, C.; Cosset, F.L.; Lavillette, D. Identification of interactions in the E1E2 heterodimer of hepatitis C virus important for cell entry. J. Biol. Chem. 2011, 286, 23865–23876. [CrossRef] [PubMed]
248. Carlsen, T.H.; Scheel, T.K.; Ramirez, S.; Foung, S.K.; Bukh, J. Characterization of hepatitis C virus recombinants with chimeric E1/E2 envelope proteins and identification of single amino acids in the E2 stem region important for entry. J. Virol. 2013, 87, 1385–1399. [CrossRef] [PubMed]
249. Steinmann, E.; Doerrbecker, J.; Friesland, M.; Riebesehl, N.; Ginkel, C.; Hillung, J.; Gentzsch, J.; Lauber, C.; Brown, R.; Frentzen, A., et al. Characterization of hepatitis C virus intra- and intergenotypic chimeras reveals a role of the glycoproteins in virus envelopment. J. Virol. 2013, 87, 13297–13306. [CrossRef] [PubMed]
250. Prokunina-Olsson, L.; Muchmore, B.; Tang, W.; Pfeiffer, R.M.; Park, H.; Dickensheets, H.; Hergott, D.; Porter-Gill, P.; Mumy, A.; Kohaar, I., et al. A variant upstream of IFNL3 (IL28B) creating a new interferon gene IFNL4 is associated with impaired clearance of hepatitis C virus. Nat. Genet. 2013, 45, 164–171. [CrossRef] [PubMed]
251. Booth, D.; George, J. Loss of function of the new interferon IFN-lambda4 may confer protection from hepatitis C. Nat. Genet. 2013, 45, 119–120. [CrossRef] [PubMed]
252. Meredith, L.W.; Farquhar, M.J.; Tarr, A.W.; McKeating, J.A. Type I interferon rapidly restricts infectious hepatitis C virus particle genesis. Hepatology 2014, 60, 1891–1901. [CrossRef] [PubMed]
253. Schoggins, J.W.; Wilson, S.J.; Panis, M.; Murphy, M.Y.; Jones, C.T.; Bieniasz, P.; Rice, C.M. A diverse range of gene products are effectors of the type I interferon antiviral response. Nature 2011, 472, 481–485. [CrossRef] [PubMed]
254. Salemi, M.; Vandamme, A.M. Hepatitis C virus evolutionary patterns studied through analysis of full-genome sequences. J. Mol. Evol. 2002, 54, 62–70. [CrossRef] [PubMed]
255. Rose, R.; Markov, P.V.; Lam, T.T.; Pybus, O.G. Viral evolution explains the associations among hepatitis C virus genotype, clinical outcomes, and human genetic variation. Infect. Genet. Evol. 2013, 20, 418–421. [CrossRef] [PubMed]
256. Taylor, D.R.; Shi, S.T.; Romano, P.R.; Barber, G.N.; Lai, M.M. Inhibition of the interferon-inducible protein kinase PKR by HCV E2 protein. Science 1999, 285, 107–110. [CrossRef] [PubMed]
257. Taylor, D.R.; Tian, B.; Romano, P.R.; Hinnebusch, A.G.; Lai, M.M.; Mathews, M.B. Hepatitis C virus envelope protein E2 does not inhibit PKR by simple competition with autophosphorylation sites in the RNA-binding domain. J. Virol. 2001, 75, 1265–1273. [CrossRef] [PubMed]
258. Afzal, S.; Idrees, M.; Akram, M.; Awan, Z.; Khubaib, B.; Aftab, M.; Fatima, Z.; Badar, S.; Hussain, A. Mutations in the E2-PePHD region of hepatitis C virus genotype-3a and correlation with response to interferon and ribavirin combination therapy in Pakistani patients. Virol. J. 2010, 7, e377. [CrossRef] [PubMed]
259. Munoz de Rueda, P.; Casado, J.; Paton, R.; Quintero, D.; Palacios, A.; Gila, A.; Quiles, R.; Leon, J.; Ruiz-Extremera, A.; Salmeron, J. Mutations in E2-PePHD, NS5A-PKRBD, NS5A-ISDR, and NS5A-V3 of hepatitis C virus genotype 1 and their relationships to pegylated interferon-ribavirin treatment responses. J. Virol. 2008, 82, 6644–6653. [CrossRef] [PubMed]
260. Ukai, K.; Ishigami, M.; Yoshioka, K.; Kawabe, N.; Katano, Y.; Hayashi, K.; Honda, T.; Yano, M.; Goto, H. Mutations in carboxy-terminal part of E2 including PKR/eIF2alpha phosphorylation homology domain and interferon sensitivity determining region of nonstructural 5A of hepatitis C virus 1b: Their correlation with response to interferon monotherapy and viral load. World J. Gastroenterol. 2006, 12, 3722–3728. [PubMed]
261. Polyak, S.J.; Nousbaum, J.B.; Larson, A.M.; Cotler, S.; Carithers, R.L., Jr.; Gretch, D.R. The protein kinase-interacting domain in the hepatitis C virus envelope glycoprotein-2 gene is highly conserved in genotype 1-infected patients treated with interferon. J. Infect. Dis. 2000, 182, 397–404. [CrossRef] [PubMed]
262. Berg, T.; Mas Marques, A.; Hohne, M.; Wiedenmann, B.; Hopf, U.; Schreier, E. Mutations in the E2-PePHD and NS5A region of hepatitis C virus type 1 and the dynamics of hepatitis C viremia decline during interferon alfa treatment. Hepatology 2000, 32, 1386–1395. [CrossRef] [PubMed]
263. Serre, S.B.; Krarup, H.B.; Bukh, J.; Gottwein, J.M. Identification of alpha interferon-induced envelope mutations of hepatitis C virus in vitro associated with increased viral fitness and interferon resistance. J. Virol. 2013, 87, 12776–12793. [CrossRef] [PubMed]
264. Perales, C.; Beach, N.M.; Gallego, I.; Soria, M.E.; Quer, J.; Esteban, J.I.; Rice, C.; Domingo, E.; Sheldon, J. Response of hepatitis C virus to long-term passage in the presence of alpha interferon: Multiple mutations and a common phenotype. J. Virol. 2013, 87, 7593–7607. [CrossRef] [PubMed]
265. Sheldon, J.; Beach, N.M.; Moreno, E.; Gallego, I.; Pineiro, D.; Martinez-Salas, E.; Gregori, J.; Quer, J.; Esteban, J.I.; Rice, C.M., et al. Increased replicative fitness can lead to decreased drug sensitivity of hepatitis C virus. J. Virol. 2014, 88, 12098–12111. [CrossRef] [PubMed]
266. Domingo, E.; Sheldon, J.; Perales, C. Viral quasispecies evolution. Microbiol. Mol. Biol. Rev. 2012, 76, 159–216. [CrossRef] [PubMed]
267. Florentin, J.; Aouar, B.; Dental, C.; Thumann, C.; Firaguay, G.; Gondois-Rey, F.; Soumelis, V.; Baumert, T.F.; Nunes, J.A.; Olive, D., et al. HCV glycoprotein E2 is a novel BDCA-2 ligand and acts as an inhibitor of IFN production by plasmacytoid dendritic cells. Blood 2012, 120, 4544–4551. [CrossRef] [PubMed]
268. Burton, D.R.; Poignard, P.; Stanfield, R.L.; Wilson, I.A. Broadly neutralizing antibodies present new prospects to counter highly antigenically diverse viruses. Science 2012, 337, 183–186. [CrossRef] [PubMed]
269. Corti, D.; Lanzavecchia, A. Broadly neutralizing antiviral antibodies. Annu. Rev. Immunol. 2013, 31, 705–742. [CrossRef] [PubMed]
270. Lake-Bakaar, G.; Dustin, L.; McKeating, J.; Newton, K.; Freeman, V.; Frost, S.D. Hepatitis C virus and alanine aminotransferase kinetics following B-lymphocyte depletion with rituximab: Evidence for a significant role of humoral immunity in the control of viremia in chronic HCV liver disease. Blood 2007, 109, 845–846. [CrossRef] [PubMed]
271. Petrarca, A.; Rigacci, L.; Caini, P.; Colagrande, S.; Romagnoli, P.; Vizzutti, F.; Arena, U.; Giannini, C.; Monti, M.; Montalto, P., et al. Safety and efficacy of rituximab in patients with hepatitis C virus-related mixed cryoglobulinemia and severe liver disease. Blood 2010, 116, 335–342. [CrossRef] [PubMed]
272. Raghuraman, S.; Park, H.; Osburn, W.O.; Winkelstein, E.; Edlin, B.R.; Rehermann, B. Spontaneous clearance of chronic hepatitis C virus infection is associated with appearance of neutralizing antibodies and reversal of T-cell exhaustion. J. Infect. Dis. 2012, 205, 763–771. [CrossRef] [PubMed]
273. Broering, T.J.; Garrity, K.A.; Boatright, N.K.; Sloan, S.E.; Sandor, F.; Thomas, W.D., Jr.; Szabo, G.; Finberg, R.W.; Ambrosino, D.M.; Babcock, G.J. Identification and characterization of broadly neutralizing human monoclonal antibodies directed against the E2 envelope glycoprotein of hepatitis C virus. J. Virol. 2009, 83, 12473–12482. [CrossRef] [PubMed]
274. Bartosch, B.; Bukh, J.; Meunier, J.C.; Granier, C.; Engle, R.E.; Blackwelder, W.C.; Emerson, S.U.; Cosset, F.L.; Purcell, R.H. In vitro assay for neutralizing antibody to hepatitis C virus: Evidence for broadly conserved neutralization epitopes. Proc. Natl. Acad. Sci. USA 2003, 100, 14199–14204. [CrossRef] [PubMed]
275. Krey, T.; Meola, A.; Keck, Z.Y.; Damier-Piolle, L.; Foung, S.K.; Rey, F.A. Structural basis of HCV neutralization by human monoclonal antibodies resistant to viral neutralization escape. PLoS Pathog. 2013, 9, e1003364. [CrossRef] [PubMed]
276. Keck, Z.Y.; Olson, O.; Gal-Tanamy, M.; Xia, J.; Patel, A.H.; Dreux, M.; Cosset, F.L.; Lemon, S.M.; Foung, S.K. A point mutation leading to hepatitis C virus escape from neutralization by a monoclonal antibody to a conserved conformational epitope. J. Virol. 2008, 82, 6067–6072. [CrossRef] [PubMed]
277. Keck, Z.Y.; Li, S.H.; Xia, J.; von Hahn, T.; Balfe, P.; McKeating, J.A.; Witteveldt, J.; Patel, A.H.; Alter, H.; Rice, C.M., et al. Mutations in hepatitis C virus E2 located outside the CD81 binding sites lead to escape from broadly neutralizing antibodies but compromise virus infectivity. J. Virol. 2009, 83, 6149–6160. [CrossRef] [PubMed]
278. Morin, T.J.; Broering, T.J.; Leav, B.A.; Blair, B.M.; Rowley, K.J.; Boucher, E.N.; Wang, Y.; Cheslock, P.S.; Knauber, M.; Olsen, D.B., et al. Human monoclonal antibody HCV1 effectively prevents and treats HCV infection in chimpanzees. PLoS Pathog. 2012, 8, e1002895. [CrossRef] [PubMed]
279. Farci, P.; Alter, H.J.; Wong, D.C.; Miller, R.H.; Govindarajan, S.; Engle, R.; Shapiro, M.; Purcell, R.H. Prevention of hepatitis C virus infection in chimpanzees after antibody-mediated in vitro neutralization. Proc. Natl. Acad. Sci. USA 1994, 91, 7792–7796. [CrossRef] [PubMed]
280. De Jong, Y.P.; Dorner, M.; Mommersteeg, M.C.; Xiao, J.W.; Balazs, A.B.; Robbins, J.B.; Winer, B.Y.; Gerges, S.; Vega, K.; Labitt, R.N., et al. Broadly neutralizing antibodies abrogate established hepatitis C virus infection. Sci. Transl. Med. 2014, 6.
281. 254ra129. [CrossRef] [PubMed]
282. Choo, Q.L.; Kuo, G.; Ralston, R.; Weiner, A.; Chien, D.; van Nest, G.; Han, J.; Berger, K.; Thudium, K.; Kuo, C. Vaccination of chimpanzees against infection by the hepatitis C virus. Proc. Natl. Acad. Sci. USA 1994, 91, 1294–1298. [CrossRef] [PubMed]
283. Houghton, M.; Abrignani, S. Prospects for a vaccine against the hepatitis C virus. Nature 2005, 436, 961–966. [CrossRef] [PubMed]
284. Houghton, M. Prospects for prophylactic and therapeutic vaccines against the hepatitis C viruses. Immunol. Rev. 2011, 239, 99–108. [CrossRef] [PubMed]
285. Meunier, J.C.; Gottwein, J.M.; Houghton, M.; Russell, R.S.; Emerson, S.U.; Bukh, J.; Purcell, R.H. Vaccine-induced cross-genotype reactive neutralizing antibodies against hepatitis C virus. J. Infect. Dis. 2011, 204, 1186–1190. [CrossRef] [PubMed]
286. Frey, S.E.; Houghton, M.; Coates, S.; Abrignani, S.; Chien, D.; Rosa, D.; Pileri, P.; Ray, R.; di Bisceglie, A.M.; Rinella, P., et al. Safety and immunogenicity of HCV E1E2 vaccine adjuvanted with MF59 administered to healthy adults. Vaccine 2010, 28, 6367–6373. [CrossRef] [PubMed]
287. Law, J.L.M.; Chen, C.; Wong, J.; Hockman, D.; Santer, D.M.; Frey, S.E.; Belshe, R.B.; Wakita, T.; Bukh, J.; Jones, C.T., et al. A Hepatitis C Virus (HCV) vaccine comprising envelope glycoproteins gpe1/gpe2 derived from a single isolate elicits broad cross-genotype neutralizing antibodies in humans. PLoS ONE 2013, 8, e59776. [CrossRef] [PubMed]
288. El-Awady, M.K.; El Gendy, M.; Waked, I.; Tabll, A.A.; El Abd, Y.; Bader El Din, N.; El Shenawy, R.; Allam, A.; Abdelhafez, T.H.; Dawood, R.M. Immunogenicity and safety of HCV E1E2 peptide vaccine in chronically HCV-infected patients who did not respond to interferon based therapy. Vaccine 2013. [CrossRef] [PubMed]
289. Akazawa, D.; Moriyama, M.; Yokokawa, H.; Omi, N.; Watanabe, N.; Date, T.; Morikawa, K.; Aizaki, H.; Ishii, K.; Kato, T., et al. Neutralizing antibodies induced by cell culture–derived hepatitis c virus protect against infection in mice. Gastroenterology 2013, 145, 447–455.e4. [CrossRef] [PubMed]
290. Saito, T.; Sherman, G.J.; Kurokohchi, K.; Guo, Z.P.; Donets, M.; Yu, M.Y.; Berzofsky, J.A.; Akatsuka, T.; Feinstone, S.M. Plasmid DNA-based immunization for hepatitis C virus structural proteins: Immune responses in mice. Gastroenterology 1997, 112, 1321–1330. [CrossRef]
291. Forns, X.; ayette, P.J.; Ma, X.; Satterfield, W.; Eder, G.; Mushahwar, I.K.; Govindarajan, S.; Davis, H.L.; Emerson, S.U.; Purcell, R.H., et al. Vaccination of chimpanzees with plasmid DNA encoding the hepatitis C virus (HCV) envelope E2 protein modified the infection after challenge with homologous monoclonal HCV. Hepatology 2000, 32, 618–625. [CrossRef] [PubMed]
292. Alvarez-Lajonchere, L.; Shoukry, N.H.; Grá, B.; Amador-Cañizares, Y.; Helle, F.; Bédard, N.; Guerra, I.; Drouin, C.; Dubuisson, J.; González-Horta, E.E., et al. Immunogenicity of CIGB-230, a therapeutic DNA vaccine preparation, in HCV-chronically infected individuals in a Phase I clinical trial. J. Viral Hepat. 2009, 16, 156–167. [CrossRef] [PubMed]
293. Alvarez-Lajonchere, L.; Dueñas-Carrera, S. Advances in DNA immunization against hepatitis C virus infection. Hum. Vaccines 2009, 5, 568–571. [CrossRef]
294. Denis, J.; Majeau, N.; Acosta-Ramirez, E.; Savard, C.; Bedard, M.-C.; Simard, S.; Lecours, K.; Bolduc, M.; Pare, C.; Willems, B., et al. Immunogenicity of papaya mosaic virus-like particles fused to a hepatitis C virus epitope: Evidence for the critical function of multimerization. Virology 2007, 363, 59–68. [CrossRef] [PubMed]
295. Muñoz, N.; Manalastas, R.; Pitisuttithum, P.; Tresukosol, D.; Monsonego, J.; Ault, K.; Clavel, C.; Luna, J.; Myers, E.; Hood, S., et al. Safety, immunogenicity, and efficacy of quadrivalent human papillomavirus (types 6, 11, 16, 18) recombinant vaccine in women aged 24–45 years: A randomised, double-blind trial. Lancet 2009, 373, 1949–1957. [CrossRef]
296. McAleer, W.J.; Buynak, E.B.; Maigetter, R.Z.; Wampler, D.E.; Miller, W.J.; Hilleman, M.R. Human hepatitis B vaccine from recombinant yeast. Nature 1984, 307, 178–180. [CrossRef] [PubMed]
297. Baumert, T.F.; Ito, S.; Wong, D.T.; Liang, T.J. Hepatitis C virus structural proteins assemble into viruslike particles in insect cells. J. Virol. 1998, 72, 3827–3836. [PubMed]
298. Zhao, W.; Liao, G.-Y.; Jiang, Y.-J.; Jiang, S.-D. Expression and self-assembly of HCV structural proteins into virus-like particles and their immunogenicity. Chin. Med. J. 2004, 117, 1217–1222. [PubMed]
299. Elmowalid, G.A.; Qiao, M.; Jeong, S.-H.; Borg, B.B.; Baumert, T.F.; Sapp, R.K.; Hu, Z.; Murthy, K.; Liang, T.J. Immunization with hepatitis C virus-like particles results in control of hepatitis C virus infection in chimpanzees. Proc. Natl. Acad. Sci. USA 2007, 104, 8427–8432. [CrossRef] [PubMed]
300. Jeong, S.-H.; Qiao, M.; Nascimbeni, M.; Hu, Z.; Rehermann, B.; Murthy, K.; Liang, T.J. Immunization with hepatitis c virus-like particles induces humoral and cellular immune responses in nonhuman primates. J. Virol. 2004, 78, 6995–7003. [CrossRef] [PubMed]
301. Qiao, M.; Murata, K.; Davis, A.R.; Jeong, S.-H.; Liang, T.J. Hepatitis C virus-like particles combined with novel adjuvant systems enhance virus-specific immune responses. Hepatology 2003, 37, 52–59. [CrossRef] [PubMed]
302. Huret, C.; Desjardins, D.; Miyalou, M.; Levacher, B.; Amadoudji Zin, M.; Bonduelle, O.; Combadière, B.; Dalba, C.; Klatzmann, D.; Bellier, B. Recombinant retrovirus-derived virus-like particle-based vaccines induce hepatitis C virus-specific cellular and neutralizing immune responses in mice. Vaccine 2013, 31, 1540–1547. [CrossRef] [PubMed]
303. Beaumont, E.; Patient, R.; Hourioux, C.; Dimier-Poisson, I.; Roingeard, P. Chimeric hepatitis B virus/hepatitis C virus envelope proteins elicit broadly neutralizing antibodies and constitute a potential bivalent prophylactic vaccine. Hepatology 2013, 57, 1303–1313. [CrossRef] [PubMed]
304. Garrone, P.; Fluckiger, A.-C.; Mangeot, P.E.; Gauthier, E.; Dupeyrot-Lacas, P.; Mancip, J.; Cangialosi, A.; Du Chene, I.; LeGrand, R.; Mangeot, I., et al. A prime-boost strategy using virus-like particles pseudotyped for hcv proteins triggers broadly neutralizing antibodies in macaques. Sci. Transl. Med. 2011, 3.
305. 94ra71. [CrossRef] [PubMed]
306. De Cassan, S.C.; Draper, S.J. Recent advances in antibody-inducing poxviral and adenoviral vectored vaccine delivery platforms for difficult disease targets. Expert Rev. Vaccines 2013, 12, 365–378. [CrossRef] [PubMed]
307. Lin, Y.; Kwon, T.; Polo, J.; Zhu, Y.-F.; Coates, S.; Crawford, K.; Dong, C.; Wininger, M.; Hall, J.; Selby, M., et al. Induction of broad CD4+ and CD8+ T-cell responses and cross- neutralizing antibodies against hepatitis C virus by vaccination with th1-adjuvanted polypeptides followed by defective alphaviral particles expressing envelope glycoproteins gpE1 and gpE2 and N. J. Virol. 2008, 82, 7492–7503. [CrossRef] [PubMed]
308. Reyes-del Valle, J.; de la Fuente, C.; Turner, M.A.; Springfeld, C.; Apte-Sengupta, S.; Frenzke, M.E.; Forest, A.; Whidby, J.; Marcotrigiano, J.; Rice, C.M., et al. Broadly neutralizing immune responses against hepatitis c virus induced by vectored measles viruses and a recombinant envelope protein booster. J. Virol. 2012, 86, 11558–11566. [CrossRef] [PubMed]
309. Chung, R.T.; Gordon, F.D.; Curry, M.P.; Schiano, T.D.; Emre, S.; Corey, K.; Markmann, J.F.; Hertl, M.; Pomposelli, J.J.; Pomfret, E.A., et al. Human monoclonal antibody MBL-HCV1 delays HCV viral rebound following liver transplantation: A randomized controlled study. Am. J. Transpl. 2013, 13, 1047–1054. [CrossRef] [PubMed]
310. Davis, G.L.; Nelson, D.R.; Terrault, N.; Pruett, T.L.; Schiano, T.D.; Fletcher, C.V.; Sapan, C.V.; Riser, L.N.; Li, Y.; Whitley, R.J., et al. A randomized, open-label study to evaluate the safety and pharmacokinetics of human hepatitis C immune globulin (Civacir) in liver transplant recipients. Liver Transpl. 2005, 11, 941–949. [CrossRef] [PubMed]
311. Schiano, T.D.; Charlton, M.; Younossi, Z.; Galun, E.; Pruett, T.; Tur-Kaspa, R.; Eren, R.; Dagan, S.; Graham, N.; Williams, P.V., et al. Monoclonal antibody HCV-AbXTL68 in patients undergoing liver transplantation for HCV: Results of a phase 2 randomized study. Liver Transpl. 2006, 12, 1381–1389. [CrossRef] [PubMed]
312. Dorner, M.; Horwitz, J.A.; Robbins, J.B.; Barry, W.T.; Feng, Q.; Mu, K.; Jones, C.T.; Schoggins, J.W.; Catanese, M.T.; Burton, D.R., et al. A genetically humanized mouse model for hepatitis C virus infection. Nature 2011, 474, 208–211. [CrossRef] [PubMed]
313. Dorner, M.; Horwitz, J.A.; Donovan, B.M.; Labitt, R.N.; Budell, W.C.; Friling, T.; Vogt, A.; Catanese, M.T.; Satoh, T.; Kawai, T., et al. Completion of the entire hepatitis C virus life cycle in genetically humanized mice. Nature 2013, 501, 237–241. [CrossRef] [PubMed]
314. Liu, J.; Bartesaghi, A.; Borgnia, M.J.; Sapiro, G.; Subramaniam, S. Molecular architecture of native HIV-1 gp120 trimers. Nature 2008, 455, 109–113. [CrossRef] [PubMed]
315. Zhu, P.; Liu, J.; Bess, J., Jr.; Chertova, E.; Lifson, J.D.; Grise, H.; Ofek, G.A.; Taylor, K.A.; Roux, K.H. Distribution and three-dimensional structure of AIDS virus envelope spikes. Nature 2006, 441, 847–852. [CrossRef] [PubMed]