1887

Abstract

The hypervariable region 1 (HVR1) comprising the first 27 aa of E2 glycoprotein is a target for neutralizing antibodies against hepatitis C virus (HCV), but the mechanisms of this neutralization in the cell-culture-infectious genotype 2a strain JFH1 HCV virus (HCVcc) system are unknown. Two rabbit polyclonal sera, R1020 and R140, recognizing the HVR1 of the genotype 1a isolates H77c and Glasgow (Gla), respectively, and a Gla HVR1-specific mouse mAb AP213 have been described previously. However, attempts to generate of antibodies to the JFH1 HVR1 were unsuccessful. Therefore, this study produced chimeric JFH1 HCVcc viruses harbouring the H77c or Gla HVR1 to assess the reactivity of antibodies to this region and their effects on virus infectivity. The inter-genotypic HVR1 swap did not significantly affect virus infectivity. The genotype 1a HVR1-specific antibodies neutralized chimeric viruses in an isolate-dependent manner, underlining the role of HVR1 in HCV infection. The neutralizing antibodies reacted mainly with the C-terminal portion of HVR1, and detailed mapping identified A17, F20 and Q21 in the Gla HVR1 sequence and T21 (and possibly L20) in the corresponding H77c sequence as key epitope residues for AP213 and R140, and R1020, respectively. Importantly, none of the antibodies inhibited binding of viral envelope glycoproteins to the best-characterized HCV receptor, CD81, or to the glycosaminoglycan attachment factors. However, the HVR1 antibodies were capable of post-attachment neutralization. Overall, this study emphasizes the role of HVR1 in HCVcc entry and provides new tools to study this region further in the context of complete virions.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.028092-0
2011-03-01
2019-10-18
Loading full text...

Full text loading...

/deliver/fulltext/jgv/92/3/494.html?itemId=/content/journal/jgv/10.1099/vir.0.028092-0&mimeType=html&fmt=ahah

References

  1. Agnello, V., Abel, G., Elfahal, M., Knight, G. B. & Zhang, Q. X. ( 1999; ). Hepatitis C virus and other Flaviviridae viruses enter cells via low density lipoprotein receptor. Proc Natl Acad Sci U S A 96, 12766–12771.[CrossRef]
    [Google Scholar]
  2. Bankwitz, D., Steinmann, E., Bitzegeio, J., Ciesek, S., Friesland, M., Herrmann, E., Zeisel, M. B., Baumert, T. F., Keck, Z. Y. & other authors ( 2010; ). Hepatitis C virus hypervariable region 1 modulates receptor interactions, conceals the CD81 binding site, and protects conserved neutralizing epitopes. J Virol 84, 5751–5763.[CrossRef]
    [Google Scholar]
  3. Barth, H., Schafer, C., Adah, M. I., Zhang, F., Linhardt, R. J., Toyoda, H., Kinoshita-Toyoda, A., Toida, T., Van Kuppevelt, T. H. & other authors ( 2003; ). Cellular binding of hepatitis C virus envelope glycoprotein E2 requires cell surface heparan sulfate. J Biol Chem 278, 41003–41012.[CrossRef]
    [Google Scholar]
  4. Barth, H., Schnober, E. K., Zhang, F., Linhardt, R. J., Depla, E., Boson, B., Cosset, F. L., Patel, A. H., Blum, H. E. & Baumert, T. F. ( 2006; ). Viral and cellular determinants of the hepatitis C virus envelope–heparan sulfate interaction. J Virol 80, 10579–10590.[CrossRef]
    [Google Scholar]
  5. Bartosch, B., Bukh, J., Meunier, J. C., Granier, C., Engle, R. E., Blackwelder, W. C., Emerson, S. U., Cosset, F. L. & Purcell, R. H. ( 2003a; ). In vitro assay for neutralizing antibody to hepatitis C virus: evidence for broadly conserved neutralization epitopes. Proc Natl Acad Sci U S A 100, 14199–14204.[CrossRef]
    [Google Scholar]
  6. Bartosch, B., Dubuisson, J. & Cosset, F. L. ( 2003b; ). Infectious hepatitis C virus pseudo-particles containing functional E1–E2 envelope protein complexes. J Exp Med 197, 633–642.[CrossRef]
    [Google Scholar]
  7. Bartosch, B., Vitelli, A., Granier, C., Goujon, C., Dubuisson, J., Pascale, S., Scarselli, E., Cortese, R., Nicosia, A. & Cosset, F. L. ( 2003c; ). 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, 41624–41630.[CrossRef]
    [Google Scholar]
  8. Bartosch, B., Verney, G., Dreux, M., Donot, P., Morice, Y., Penin, F., Pawlotsky, J. M., Lavillette, D. & Cosset, F. L. ( 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, 8217–8229.[CrossRef]
    [Google Scholar]
  9. Basu, A., Beyene, A., Meyer, K. & Ray, R. ( 2004; ). The hypervariable region 1 of the E2 glycoprotein of hepatitis C virus binds to glycosaminoglycans, but this binding does not lead to infection in a pseudotype system. J Virol 78, 4478–4486.[CrossRef]
    [Google Scholar]
  10. Bukh, J., Miller, R. H. & Purcell, R. H. ( 1995; ). Genetic heterogeneity of hepatitis C virus: quasispecies and genotypes. Semin Liver Dis 15, 41–63.[CrossRef]
    [Google Scholar]
  11. Callens, N., Ciczora, Y., Bartosch, B., Vu-Dac, N., Cosset, F. L., Pawlotsky, J. M., Penin, F. & Dubuisson, J. ( 2005; ). Basic residues in hypervariable region 1 of hepatitis C virus envelope glycoprotein E2 contribute to virus entry. J Virol 79, 15331–15341.[CrossRef]
    [Google Scholar]
  12. Chang, K. S., 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, 13783–13793.[CrossRef]
    [Google Scholar]
  13. Clackson, T. & Wells, J. A. ( 1995; ). A hot spot of binding energy in a hormone–receptor interface. Science 267, 383–386.[CrossRef]
    [Google Scholar]
  14. Clayton, R. F., Owsianka, A., Aitken, J., Graham, S., Bhella, D. & Patel, A. H. ( 2002; ). Analysis of antigenicity and topology of E2 glycoprotein present on recombinant hepatitis C virus-like particles. J Virol 76, 7672–7682.[CrossRef]
    [Google Scholar]
  15. Cocquerel, L., Meunier, J. C., Pillez, A., Wychowski, C. & Dubuisson, J. ( 1998; ). A retention signal necessary and sufficient for endoplasmic reticulum localization maps to the transmembrane domain of hepatitis C virus glycoprotein E2. J Virol 72, 2183–2191.
    [Google Scholar]
  16. Dhillon, S., Witteveldt, J., Gatherer, D., Owsianka, A. M., Zeisel, M. B., Zahid, M. N., Rychlowska, M., Foung, S. K., Baumert, T. F. & other authors ( 2010; ). Mutations within a conserved region of the hepatitis C virus E2 glycoprotein that influence virus–receptor interactions and sensitivity to neutralizing antibodies. J Virol 84, 5494–5507.[CrossRef]
    [Google Scholar]
  17. Dreux, M., Pietschmann, T., Granier, C., Voisset, C., Ricard-Blum, S., Mangeot, P. E., Keck, Z., Foung, S., Vu-Dac, N. & other authors ( 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, 18285–18295.[CrossRef]
    [Google Scholar]
  18. 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. ( 2007; ). Claudin-1 is a hepatitis C virus co-receptor required for a late step in entry. Nature 446, 801–805.[CrossRef]
    [Google Scholar]
  19. Farci, P., Shimoda, A., Wong, D., Cabezon, T., De Gioannis, D., Strazzera, A., Shimizu, Y., Shapiro, M., Alter, H. J. & Purcell, R. H. ( 1996; ). 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 U S A 93, 15394–15399.[CrossRef]
    [Google Scholar]
  20. Farci, P., Shimoda, A., Coiana, A., Diaz, G., Peddis, G., Melpolder, J. C., Strazzera, A., Chien, D. Y., Munoz, S. J. & other authors ( 2000; ). The outcome of acute hepatitis C predicted by the evolution of the viral quasispecies. Science 288, 339–344.[CrossRef]
    [Google Scholar]
  21. Flint, M., Dubuisson, J., Maidens, C., Harrop, R., Guile, G. R., Borrow, P. & McKeating, J. A. ( 2000; ). Functional characterization of intracellular and secreted forms of a truncated hepatitis C virus E2 glycoprotein. J Virol 74, 702–709.[CrossRef]
    [Google Scholar]
  22. Forns, X., Allander, T., Rohwer-Nutter, P. & Bukh, J. ( 2000a; ). Characterization of modified hepatitis C virus E2 proteins expressed on the cell surface. Virology 274, 75–85.[CrossRef]
    [Google Scholar]
  23. Forns, X., Thimme, R., Govindarajan, S., Emerson, S. U., Purcell, R. H., Chisari, F. V. & Bukh, J. ( 2000b; ). 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 U S A 97, 13318–13323.[CrossRef]
    [Google Scholar]
  24. Haberstroh, A., Schnober, E. K., Zeisel, M. B., Carolla, P., Barth, H., Blum, H. E., Cosset, F. L., Koutsoudakis, G., Bartenschlager, R. & other authors ( 2008; ). Neutralizing host responses in hepatitis C virus infection target viral entry at postbinding steps and membrane fusion. Gastroenterology 135, 1719–1728.[CrossRef]
    [Google Scholar]
  25. Hijikata, M., Kato, N., Ootsuyama, Y., Nakagawa, M., Ohkoshi, S. & Shimotohno, K. ( 1991; ). Hypervariable regions in the putative glycoprotein of hepatitis C virus. Biochem Biophys Res Commun 175, 220–228.[CrossRef]
    [Google Scholar]
  26. Hsu, M., Zhang, J., Flint, M., Logvinoff, C., Cheng-Mayer, C., Rice, C. M. & McKeating, J. A. ( 2003; ). Hepatitis C virus glycoproteins mediate pH-dependent cell entry of pseudotyped retroviral particles. Proc Natl Acad Sci U S A 100, 7271–7276.[CrossRef]
    [Google Scholar]
  27. Iro, M., Witteveldt, J., Angus, A. G., Woerz, I., Kaul, A., Bartenschlager, R. & Patel, A. H. ( 2009; ). A reporter cell line for rapid and sensitive evaluation of hepatitis C virus infectivity and replication. Antiviral Res 83, 148–155.[CrossRef]
    [Google Scholar]
  28. Johansson, D. X., Voisset, C., Tarr, A. W., Aung, M., Ball, J. K., Dubuisson, J. & Persson, M. A. ( 2007; ). Human combinatorial libraries yield rare antibodies that broadly neutralize hepatitis C virus. Proc Natl Acad Sci U S A 104, 16269–16274.[CrossRef]
    [Google Scholar]
  29. Kato, T., Date, T., Murayama, A., Morikawa, K., Akazawa, D. & Wakita, T. ( 2006; ). Cell culture and infection system for hepatitis C virus. Nat Protoc 1, 2334–2339.[CrossRef]
    [Google Scholar]
  30. Keck, Z. Y., Xia, J., Cai, Z., Li, T. K., Owsianka, A. M., Patel, A. H., Luo, G. & Foung, S. K. ( 2007; ). Immunogenic and functional organization of hepatitis C virus (HCV) glycoprotein E2 on infectious HCV virions. J Virol 81, 1043–1047.[CrossRef]
    [Google Scholar]
  31. 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, 5308–5320.[CrossRef]
    [Google Scholar]
  32. Kurosaki, M., Enomoto, N., Marumo, F. & Sato, C. ( 1993; ). Rapid sequence variation of the hypervariable region of hepatitis C virus during the course of chronic infection. Hepatology 18, 1293–1299.[CrossRef]
    [Google Scholar]
  33. Lavillette, D., Tarr, A. W., Voisset, C., Donot, P., Bartosch, B., Bain, C., Patel, A. H., Dubuisson, J., Ball, J. K. & Cosset, F. L. ( 2005; ). Characterization of host-range and cell entry properties of the major genotypes and subtypes of hepatitis C virus. Hepatology 41, 265–274.[CrossRef]
    [Google Scholar]
  34. Law, M., Maruyama, T., Lewis, J., Giang, E., Tarr, A. W., Stamataki, Z., Gastaminza, P., Chisari, F. V., Jones, I. M. & other authors ( 2008; ). Broadly neutralizing antibodies protect against hepatitis C virus quasispecies challenge. Nat Med 14, 25–27.[CrossRef]
    [Google Scholar]
  35. Li, C. & Allain, J. P. ( 2005; ). Chimeric monoclonal antibodies to hypervariable region 1 of hepatitis C virus. J Gen Virol 86, 1709–1716.[CrossRef]
    [Google Scholar]
  36. Li, C., Candotti, D. & Allain, J. P. ( 2001; ). Production and characterization of monoclonal antibodies specific for a conserved epitope within hepatitis C virus hypervariable region 1. J Virol 75, 12412–12420.[CrossRef]
    [Google Scholar]
  37. 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. & other authors ( 2005; ). Complete replication of hepatitis C virus in cell culture. Science 309, 623–626.[CrossRef]
    [Google Scholar]
  38. Liu, S., Yang, W., Shen, L., Turner, J. R., Coyne, C. B. & 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, 2011–2014.[CrossRef]
    [Google Scholar]
  39. Macdonald, A., Crowder, K., Street, A., McCormick, C., Saksela, K. & Harris, M. ( 2003; ). The hepatitis C virus non-structural NS5A protein inhibits activating protein-1 function by perturbing ras–ERK pathway signaling. J Biol Chem 278, 17775–17784.[CrossRef]
    [Google Scholar]
  40. Mancini, N., Diotti, R. A., Perotti, M., Sautto, G., Clementi, N., Nitti, G., Patel, A. H., Ball, J. K., Clementi, M. & Burioni, R. ( 2009; ). Hepatitis C virus (HCV) infection may elicit neutralizing antibodies targeting epitopes conserved in all viral genotypes. PLoS ONE 4, e8254.[CrossRef]
    [Google Scholar]
  41. McCaffrey, K., Boo, I., Poumbourios, P. & Drummer, H. E. ( 2007; ). Expression and characterization of a minimal hepatitis C virus glycoprotein E2 core domain that retains CD81 binding. J Virol 81, 9584–9590.[CrossRef]
    [Google Scholar]
  42. Meertens, L., Bertaux, C., Cukierman, L., Cormier, E., Lavillette, D., Cosset, F. L. & Dragic, T. ( 2008; ). The tight junction proteins claudin-1, -6, and -9 are entry cofactors for hepatitis C virus. J Virol 82, 3555–3560.[CrossRef]
    [Google Scholar]
  43. Moradpour, D., Penin, F. & Rice, C. M. ( 2007; ). Replication of hepatitis C virus. Nat Rev Microbiol 5, 453–463.[CrossRef]
    [Google Scholar]
  44. Nakabayashi, H., Taketa, K., Miyano, K., Yamane, T. & Sato, J. ( 1982; ). Growth of human hepatoma cells lines with differentiated functions in chemically defined medium. Cancer Res 42, 3858–3863.
    [Google Scholar]
  45. Owsianka, A., Clayton, R. F., Loomis-Price, L. D., McKeating, J. A. & Patel, A. H. ( 2001; ). Functional analysis of hepatitis C virus E2 glycoproteins and virus-like particles reveals structural dissimilarities between different forms of E2. J Gen Virol 82, 1877–1883.
    [Google Scholar]
  46. Owsianka, A., Tarr, A. W., Juttla, V. S., Lavillette, D., Bartosch, B., Cosset, F. L., Ball, J. K. & Patel, A. H. ( 2005; ). Monoclonal antibody AP33 defines a broadly neutralizing epitope on the hepatitis C virus E2 envelope glycoprotein. J Virol 79, 11095–11104.[CrossRef]
    [Google Scholar]
  47. Owsianka, A. M., Tarr, A. W., Keck, Z. Y., Li, T. K., Witteveldt, J., Adair, R., Foung, S. K., Ball, J. K. & Patel, A. H. ( 2008; ). Broadly neutralizing human monoclonal antibodies to the hepatitis C virus E2 glycoprotein. J Gen Virol 89, 653–659.[CrossRef]
    [Google Scholar]
  48. Patel, A. H., Wood, J., Penin, F., Dubuisson, J. & McKeating, J. A. ( 2000; ). Construction and characterization of chimeric hepatitis C virus E2 glycoproteins: analysis of regions critical for glycoprotein aggregation and CD81 binding. J Gen Virol 81, 2873–2883.
    [Google Scholar]
  49. Pawlotsky, J. M. ( 2003; ). Hepatitis C virus genetic variability: pathogenic and clinical implications. Clin Liver Dis 7, 45–66.[CrossRef]
    [Google Scholar]
  50. Penin, F., Combet, C., Germanidis, G., Frainais, P. O., Deleage, G. & Pawlotsky, J. M. ( 2001; ). Conservation of the conformation and positive charges of hepatitis C virus E2 envelope glycoprotein hypervariable region 1 points to a role in cell attachment. J Virol 75, 5703–5710.[CrossRef]
    [Google Scholar]
  51. Perotti, M., Mancini, N., Diotti, R. A., Tarr, A. W., Ball, J. K., Owsianka, A., Adair, R., Patel, A. H., Clementi, M. & Burioni, R. ( 2008; ). Identification of a broadly cross-reacting and neutralizing human monoclonal antibody directed against the hepatitis C virus E2 protein. J Virol 82, 1047–1052.[CrossRef]
    [Google Scholar]
  52. Pileri, P., Uematsu, Y., Campagnoli, S., Galli, G., Falugi, F., Petracca, R., Weiner, A. J., Houghton, M., Rosa, D. & other authors ( 1998; ). Binding of hepatitis C virus to CD81. Science 282, 938–941.[CrossRef]
    [Google Scholar]
  53. Ploss, A., Evans, M. J., Gaysinskaya, V. A., Panis, M., You, H., de Jong, Y. P. & Rice, C. M. ( 2009; ). Human occludin is a hepatitis C virus entry factor required for infection of mouse cells. Nature 457, 882–886.[CrossRef]
    [Google Scholar]
  54. Roccasecca, R., Ansuini, H., Vitelli, A., Meola, A., Scarselli, E., Acali, S., Pezzanera, M., Ercole, B. B., McKeating, J. & other authors ( 2003; ). Binding of the hepatitis C virus E2 glycoprotein to CD81 is strain specific and is modulated by a complex interplay between hypervariable regions 1 and 2. J Virol 77, 1856–1867.[CrossRef]
    [Google Scholar]
  55. Rosa, D., Campagnoli, S., Moretto, C., Guenzi, E., Cousens, L., Chin, M., Dong, C., Weiner, A. J., Lau, J. Y. & other authors ( 1996; ). A quantitative test to estimate neutralizing antibodies to the hepatitis C virus: cytofluorimetric assessment of envelope glycoprotein 2 binding to target cells. Proc Natl Acad Sci U S A 93, 1759–1763.[CrossRef]
    [Google Scholar]
  56. Scarselli, E., Ansuini, H., Cerino, R., Roccasecca, R. M., 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, 5017–5025.[CrossRef]
    [Google Scholar]
  57. Schofield, D. J., Bartosch, B., Shimizu, Y. K., Allander, T., Alter, H. J., Emerson, S. U., Cosset, F. L. & Purcell, R. H. ( 2005; ). Human monoclonal antibodies that react with the E2 glycoprotein of hepatitis C virus and possess neutralizing activity. Hepatology 42, 1055–1062.[CrossRef]
    [Google Scholar]
  58. Shimizu, Y. K., Hijikata, M., Iwamoto, A., Alter, H. J., Purcell, R. H. & Yoshikura, H. ( 1994; ). Neutralizing antibodies against hepatitis C virus and the emergence of neutralization escape mutant viruses. J Virol 68, 1494–1500.
    [Google Scholar]
  59. Simmonds, P. ( 1995; ). Variability of hepatitis C virus. Hepatology 21, 570–583.[CrossRef]
    [Google Scholar]
  60. 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. ( 2006; ). Characterization of the hepatitis C virus E2 epitope defined by the broadly neutralizing monoclonal antibody AP33. Hepatology 43, 592–601.[CrossRef]
    [Google Scholar]
  61. Troesch, M., Meunier, I., Lapierre, P., Lapointe, N., Alvarez, F., Boucher, M. & Soudeyns, H. ( 2006; ). Study of a novel hypervariable region in hepatitis C virus (HCV) E2 envelope glycoprotein. Virology 352, 357–367.[CrossRef]
    [Google Scholar]
  62. Vieyres, G., Angus, A. G., Haberstroh, A., Baumert, T. F., Dubuisson, J. & Patel, A. H. ( 2009; ). Rapid synchronization of hepatitis C virus infection by magnetic adsorption. J Virol Methods 157, 69–79.[CrossRef]
    [Google Scholar]
  63. 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, 7793–7799.[CrossRef]
    [Google Scholar]
  64. Wakita, T., Pietschmann, T., Kato, T., Date, T., Miyamoto, M., Zhao, Z., Murthy, K., Habermann, A., Krausslich, H. G. & other authors ( 2005; ). Production of infectious hepatitis C virus in tissue culture from a cloned viral genome. Nat Med 11, 791–796.[CrossRef]
    [Google Scholar]
  65. Weiner, A. J., Brauer, M. J., Rosenblatt, J., Richman, K. H., Tung, J., Crawford, K., Bonino, F., Saracco, G., Choo, Q. L. & other authors ( 1991; ). Variable and hypervariable domains are found in the regions of HCV corresponding to the flavivirus envelope and NS1 proteins and the pestivirus envelope glycoproteins. Virology 180, 842–848.[CrossRef]
    [Google Scholar]
  66. Weiner, A. J., Geysen, H. M., Christopherson, C., Hall, J. E., Mason, T. J., Saracco, G., Bonino, F., Crawford, K., Marion, C. D. & other authors ( 1992; ). Evidence for immune selection of hepatitis C virus (HCV) putative envelope glycoprotein variants: potential role in chronic HCV infections. Proc Natl Acad Sci U S A 89, 3468–3472.[CrossRef]
    [Google Scholar]
  67. Yanagi, M., Purcell, R. H., Emerson, S. U. & Bukh, J. ( 1997; ). Transcripts from a single full-length cDNA clone of hepatitis C virus are infectious when directly transfected into the liver of a chimpanzee. Proc Natl Acad Sci U S A 94, 8738–8743.[CrossRef]
    [Google Scholar]
  68. Zeisel, M. B., Koutsoudakis, G., Schnober, E. K., Haberstroh, A., Blum, H. E., Cosset, F. L., Wakita, T., Jaeck, D., Doffoel, M. & other authors ( 2007; ). Scavenger receptor class B type I is a key host factor for hepatitis C virus infection required for an entry step closely linked to CD81. Hepatology 46, 1722–1731.[CrossRef]
    [Google Scholar]
  69. 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, 12465–12471.[CrossRef]
    [Google Scholar]
  70. Zhong, J., Gastaminza, P., Cheng, G., Kapadia, S., Kato, T., Burton, D. R., Wieland, S. F., Uprichard, S. L., Wakita, T. & Chisari, F. V. ( 2005; ). Robust hepatitis C virus infection in vitro. Proc Natl Acad Sci U S A 102, 9294–9299.[CrossRef]
    [Google Scholar]
  71. Zibert, A., Schreier, E. & Roggendorf, M. ( 1995; ). Antibodies in human sera specific to hypervariable region 1 of hepatitis C virus can block viral attachment. Virology 208, 653–661.[CrossRef]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.028092-0
Loading
/content/journal/jgv/10.1099/vir.0.028092-0
Loading

Data & Media loading...

Supplements

vol. , part 3, pp. 494 - 506

Anti-HVR1 antibodies neutralize chimeric HCVpp infection [PDF](50 KB)



PDF

Most Cited This Month

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error