1887

Abstract

A better understanding of natural variation in neutralization resistance and fitness of diverse hepatitis C virus (HCV) envelope (E1E2) variants will be critical to guide rational development of an HCV vaccine. This work has been hindered by inadequate genetic diversity in viral panels and by a lack of standardization of HCV entry assays. Neutralization assays generally use lentiviral pseudoparticles expressing HCV envelope proteins (HCVpp) or chimeric full-length viruses that are replication competent in cell culture (HCVcc). There have been few systematic comparisons of specific infectivities of E1E2-matched HCVcc and HCVpp, and to our knowledge, neutralization of E1E2-matched HCVpp and HCVcc has never been compared using a diverse panel of human broadly neutralizing monoclonal antibodies (bNAbs) targeting distinct epitopes. Here, we describe an efficient method for introduction of naturally occurring E1E2 genes into a full-length HCV genome, producing replication-competent chimeric HCVcc. We generated diverse panels of E1E2-matched HCVcc and HCVpp and measured the entry-mediating fitness of E1E2 variants using the two systems. We also compared neutralization of E1E2-matched HCVcc and HCVpp by a diverse panel of human bNAbs targeting epitopes across E1E2. We found no correlation between specific infectivities of E1E2-matched HCVcc versus HCVpp, but found a very strong positive correlation between relative neutralization resistance of these same E1E2-matched HCVcc and HCVpp variants. These results suggest that quantitative comparisons of neutralization resistance of E1E2 variants can be made with confidence using either HCVcc or HCVpp, allowing the use of either or both systems to maximize diversity of neutralization panels.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/jgv.0.000608
2016-11-10
2019-10-14
Loading full text...

Full text loading...

/deliver/fulltext/jgv/97/11/2883.html?itemId=/content/journal/jgv/10.1099/jgv.0.000608&mimeType=html&fmt=ahah

References

  1. Armstrong G. L., Wasley A., Simard E. P., McQuillan G. M., Kuhnert W. L., Alter M. J..( 2006;). The prevalence of hepatitis C virus infection in the United States, 1999 through 2002. . Ann Intern Med 144: 705–714. [CrossRef] [PubMed]
    [Google Scholar]
  2. Averhoff F. M., Glass N., Holtzman D..( 2012;). Global burden of hepatitis C: considerations for healthcare providers in the United States. . Clin Infect Dis 55: S10–S15. [CrossRef] [PubMed]
    [Google Scholar]
  3. Bailey J. R., Wasilewski L. N., Snider A. E., El-Diwany R., Osburn W. O., Keck Z., Foung S. K. H., Ray S. C..( 2015a;). Naturally selected hepatitis C virus polymorphisms confer broad neutralizing antibody resistance. . J Clin Invest 125: 437–447. [CrossRef]
    [Google Scholar]
  4. Bailey J. R., Dowd K. A., Snider A. E., Osburn W. O., Mehta S. H., Kirk G. D., Thomas D. L., Ray S. C..( 2015b;). CD4 T-cell-dependent reduction in hepatitis C virus-specific neutralizing antibody responses after coinfection with human immunodeficiency virus. . J Infect Dis 212: 914–923.[CrossRef]
    [Google Scholar]
  5. Bartosch B., Vitelli A., Granier C., Goujon C., Dubuisson J., Pascale S., Scarselli E., Cortese R., Nicosia A., Cosset F. L..( 2003;). 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] [PubMed]
    [Google Scholar]
  6. Boyer A., Dumans A., Beaumont E., Etienne L., Roingeard P., Meunier J. C..( 2014;). The association of hepatitis C virus glycoproteins with apolipoproteins E and B early in assembly is conserved in lipoviral particles. . J Biol Chem 289: 18904–18913. [CrossRef] [PubMed]
    [Google Scholar]
  7. 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. et al.( 2011;). Neutralizing antibody-resistant hepatitis C virus cell-to-cell transmission. . J Virol 85: 596–605. [CrossRef] [PubMed]
    [Google Scholar]
  8. Bukh J., Pietschmann T., Lohmann V., Krieger N., Faulk K., Engle R. E., Govindarajan S., Shapiro M., St Claire M., Bartenschlager R..( 2002;). Mutations that permit efficient replication of hepatitis C virus RNA in Huh-7 cells prevent productive replication in chimpanzees. . Proc Natl Acad Sci U S A 99: 14416–14421. [CrossRef] [PubMed]
    [Google Scholar]
  9. Carlsen T. H., Scheel T. K., Ramirez S., Foung S. K., Bukh J..( 2013;). 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 87: 1385–1399. [CrossRef] [PubMed]
    [Google Scholar]
  10. Carlsen T. H., Pedersen J., Prentoe J. C., Giang E., Keck Z. Y., Mikkelsen L. S., Law M., Foung S. K., Bukh J..( 2014;). Breadth of neutralization and synergy of clinically relevant human monoclonal antibodies against HCV genotypes 1a, 1b, 2a, 2b, 2c, and 3a. . Hepatology 60: 1551–1562. [CrossRef] [PubMed]
    [Google Scholar]
  11. Catanese M. T., Uryu K., Kopp M., Edwards T. J., Andrus L., Rice W. J., Silvestry M., Kuhn R. J., Rice C. M..( 2013;). Ultrastructural analysis of hepatitis C virus particles. . Proc Natl Acad Sci U S A 110: 9505–9510. [CrossRef] [PubMed]
    [Google Scholar]
  12. Cormier E. G., Tsamis F., Kajumo F., Durso R. J., Gardner J. P., Dragic T..( 2004;). CD81 is an entry coreceptor for hepatitis C virus. . Proc Natl Acad Sci U S A 101: 7270–7274. [CrossRef] [PubMed]
    [Google Scholar]
  13. Dowd K. A., Netski D. M., Wang X. H., Cox A. L., Ray S. C..( 2009;). Selection pressure from neutralizing antibodies drives sequence evolution during acute infection with hepatitis C virus. . Gastroenterology 136: 2377–2386. [CrossRef] [PubMed]
    [Google Scholar]
  14. Falkowska E., Kajumo F., Garcia E., Reinus J., Dragic T..( 2007;). Hepatitis C virus envelope glycoprotein E2 glycans modulate entry, CD81 binding, and neutralization. . J Virol 81: 8072–8079. [CrossRef] [PubMed]
    [Google Scholar]
  15. Fauvelle C., Felmlee D. J., Crouchet E., Lee J., Heydmann L., Lefèvre M., Magri A., Hiet M. S., Fofana I. et al.( 2016;). Apolipoprotein E mediates evasion from hepatitis C virus neutralizing antibodies. . Gastroenterology 150: 206–217. [CrossRef] [PubMed]
    [Google Scholar]
  16. Fofana I., Fafi-Kremer S., Carolla P., Fauvelle C., Zahid M. N., Turek M., Heydmann L., Cury K., Hayer J. et al.( 2012;). Mutations that alter use of hepatitis C virus cell entry factors mediate escape from neutralizing antibodies. . Gastroenterology 143: 223–233. [CrossRef] [PubMed]
    [Google Scholar]
  17. Forns X., Payette P. J., Ma X., Satterfield W., Eder G., Mushahwar I. K., Govindarajan S., Davis H. L., Emerson S. U. et al.( 2000;). 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 32: 618–625. [CrossRef] [PubMed]
    [Google Scholar]
  18. Giang E., Dorner M., Prentoe J. C., Dreux M., Evans M. J., Bukh J., Rice C. M., Ploss A., Burton D. R., Law M..( 2012;). Human broadly neutralizing antibodies to the envelope glycoprotein complex of hepatitis C virus. . Proc Natl Acad Sci U S A 109: 6205–6210. [CrossRef] [PubMed]
    [Google Scholar]
  19. Gottwein J. M., Scheel T. K., Hoegh A. M., Lademann J. B., Eugen-Olsen J., Lisby G., Bukh J..( 2007;). Robust hepatitis C genotype 3a cell culture releasing adapted intergenotypic 3a/2a (S52/JFH1) viruses. . Gastroenterology 133: 1614–1626. [CrossRef] [PubMed]
    [Google Scholar]
  20. Gottwein J. M., Scheel T. K., Jensen T. B., Lademann J. B., Prentoe J. C., Knudsen M. L., Hoegh A. M., Bukh J..( 2009;). 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 49: 364–377. [CrossRef] [PubMed]
    [Google Scholar]
  21. Hadlock K. G., Lanford R. E., Perkins S., Rowe J., Yang Q., Levy S., Pileri P., Abrignani S., Foung S. K..( 2000;). Human monoclonal antibodies that inhibit binding of hepatitis C virus E2 protein to CD81 and recognize conserved conformational epitopes. . J Virol 74: 10407–10416. [CrossRef] [PubMed]
    [Google Scholar]
  22. Hishiki T., Shimizu Y., Tobita R., Sugiyama K., Ogawa K., Funami K., Ohsaki Y., Fujimoto T., Takaku H. et al.( 2010;). Infectivity of hepatitis C virus is influenced by association with apolipoprotein E isoforms. . J Virol 84: 12048–12057. [CrossRef] [PubMed]
    [Google Scholar]
  23. Holmberg S. D., Spradling P. R., Moorman A. C., Denniston M. M..( 2013;). Hepatitis C in the United States. . N Engl J Med 368: 1859–1861. [CrossRef] [PubMed]
    [Google Scholar]
  24. 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] [PubMed]
    [Google Scholar]
  25. Jiang J., Luo G..( 2009;). Apolipoprotein E but not B is required for the formation of infectious hepatitis C virus particles. . J Virol 83: 12680–12691. [CrossRef] [PubMed]
    [Google Scholar]
  26. Jiang J., Cun W., Wu X., Shi Q., Tang H., Luo G..( 2012;). Hepatitis C virus attachment mediated by apolipoprotein E binding to cell surface heparan sulfate. . J Virol 86: 7256–7267. [CrossRef] [PubMed]
    [Google Scholar]
  27. Keck Z. Y., Olson O., Gal-Tanamy M., Xia J., Patel A. H., Dreux M., Cosset F. L., Lemon S. M., Foung S. K..( 2008;). A point mutation leading to hepatitis C virus escape from neutralization by a monoclonal antibody to a conserved conformational epitope. . J Virol 82: 6067–6072. [CrossRef] [PubMed]
    [Google Scholar]
  28. Keck Z. Y., Li S. H., Xia J., von Hahn T., Balfe P., McKeating J. A., Witteveldt J., Patel A. H., Alter H. et al.( 2009;). 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 83: 6149–6160. [CrossRef] [PubMed]
    [Google Scholar]
  29. Keck Z. Y., Xia J., Wang Y., Wang W., Krey T., Prentoe J., Carlsen T., Li A. Y., Patel A. H. et al.( 2012;). 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 8: e1002653. [CrossRef] [PubMed]
    [Google Scholar]
  30. Keck Z., Wang W., Wang Y., Lau P., Carlsen T. H., Prentoe J., Xia J., Patel A. H., Bukh J., Foung S. K..( 2013;). 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 87: 37–51. [CrossRef] [PubMed]
    [Google Scholar]
  31. Lavie M., Sarrazin S., Montserret R., Descamps V., Baumert T. F., Duverlie G., Séron K., Penin F., Dubuisson J..( 2014;). Identification of conserved residues in hepatitis C virus envelope glycoprotein E2 that modulate virus dependence on CD81 and SRB1 entry factors. . J Virol 88: 10584–10597. [CrossRef] [PubMed]
    [Google Scholar]
  32. Law M., Maruyama T., Lewis J., Giang E., Tarr A. W., Stamataki Z., Gastaminza P., Chisari F. V., Jones I. M. et al.( 2008;). Broadly neutralizing antibodies protect against hepatitis C virus quasispecies challenge. . Nat Med 14: 25–27. [CrossRef] [PubMed]
    [Google Scholar]
  33. Lindenbach B. D., Meuleman P., Ploss A., Vanwolleghem T., Syder A. J., McKeating J. A., Lanford R. E., Feinstone S. M., Major M. E. et al.( 2006;). Cell culture-grown hepatitis C virus is infectious in vivo and can be recultured in vitro. . Proc Natl Acad Sci U S A 103: 3805–3809. [CrossRef] [PubMed]
    [Google Scholar]
  34. Logvinoff C., Major M. E., Oldach D., Heyward S., Talal A., Balfe P., Feinstone S. M., Alter H., Rice C. M., McKeating J. A..( 2004;). Neutralizing antibody response during acute and chronic hepatitis C virus infection. . Proc Natl Acad Sci U S A 101: 10149–10154. [CrossRef] [PubMed]
    [Google Scholar]
  35. Mathiesen C. K., Jensen T. B., Prentoe J., Krarup H., Nicosia A., Law M., Bukh J., Gottwein J. M..( 2014;). Production and characterization of high-titer serum-free cell culture grown hepatitis C virus particles of genotype 1-6. . Virology 458–459: 190–208. [CrossRef] [PubMed]
    [Google Scholar]
  36. Mathiesen C. K., Prentoe J., Meredith L. W., Jensen T. B., Krarup H., McKeating J. A., Gottwein J. M., Bukh J..( 2015;). Adaptive mutations enhance assembly and cell-to-cell transmission of a high-titer hepatitis C virus genotype 5a core-NS2 JFH1-based recombinant. . J Virol 89: 7758–7775. [CrossRef] [PubMed]
    [Google Scholar]
  37. McClure C. P., Urbanowicz R. A., King B. J., Cano-Crespo S., Tarr A. W., Ball J. K..( 2016;). Flexible and rapid construction of viral chimeras applied to hepatitis C virus. . J Gen Virol 97: 2187–2193. [CrossRef] [PubMed]
    [Google Scholar]
  38. McKeating J. A., Zhang L. Q., Logvinoff C., Flint M., Zhang J., Yu J., Butera D., Ho D. D., Dustin L. B. et al.( 2004;). Diverse hepatitis C virus glycoproteins mediate viral infection in a CD81-dependent manner. . J Virol 78: 8496–8505. [CrossRef] [PubMed]
    [Google Scholar]
  39. 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..( 2005;). Evidence for cross-genotype neutralization of hepatitis C virus pseudo-particles and enhancement of infectivity by apolipoprotein C1. . Proc Natl Acad Sci U S A 102: 4560–4565. [CrossRef] [PubMed]
    [Google Scholar]
  40. Meunier J. C., Russell R. S., Engle R. E., Faulk K. N., Purcell R. H., Emerson S. U..( 2008;). Apolipoprotein c1 association with hepatitis C virus. . J Virol 82: 9647–9656. [CrossRef] [PubMed]
    [Google Scholar]
  41. 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. et al.( 2012;). Human monoclonal antibody HCV1 effectively prevents and treats HCV infection in chimpanzees. . PLoS Pathog 8: e1002895. [CrossRef] [PubMed]
    [Google Scholar]
  42. Osburn W. O., Snider A. E., Wells B. L., Latanich R., Bailey J. R., Thomas D. L., Cox A. L., Ray S. C..( 2014;). Clearance of hepatitis C infection is associated with the early appearance of broad neutralizing antibody responses. . Hepatology 59: 2140–2151. [CrossRef] [PubMed]
    [Google Scholar]
  43. Pestka J. M., Zeisel M. B., Bläser E., Schürmann P., Bartosch B., Cosset F. L., Patel A. H., Meisel H., Baumert J. et al.( 2007;). Rapid induction of virus-neutralizing antibodies and viral clearance in a single-source outbreak of hepatitis C. . Proc Natl Acad Sci U S A 104: 6025–6030. [CrossRef] [PubMed]
    [Google Scholar]
  44. Podevin P., Carpentier A., Pène V., Aoudjehane L., Carrière M., Zaïdi S., Hernandez C., Calle V., Méritet J. F. et al.( 2010;). Production of infectious hepatitis C virus in primary cultures of human adult hepatocytes. . Gastroenterology 139: 1355–1364. [CrossRef] [PubMed]
    [Google Scholar]
  45. Russell R. S., Kawaguchi K., Meunier J. C., Takikawa S., Faulk K., Bukh J., Purcell R. H., Emerson S. U..( 2009;). 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 16: 621–632. [CrossRef] [PubMed]
    [Google Scholar]
  46. Scheel T. K., Gottwein J. M., Jensen T. B., Prentoe J. C., Hoegh A. M., Alter H. J., Eugen-Olsen J., Bukh J..( 2008;). Development of JFH1-based cell culture systems for hepatitis C virus genotype 4a and evidence for cross-genotype neutralization. . Proc Natl Acad Sci U S A 105: 997–1002. [CrossRef] [PubMed]
    [Google Scholar]
  47. Scheel T. K., Gottwein J. M., Carlsen T. H., Li Y. P., Jensen T. B., Spengler U., Weis N., Bukh J..( 2011;). Efficient culture adaptation of hepatitis C virus recombinants with genotype-specific core-NS2 by using previously identified mutations. . J Virol 85: 2891–2906. [CrossRef] [PubMed]
    [Google Scholar]
  48. Shan L., Rabi S. A., Laird G. M., Eisele E. E., Zhang H., Margolick J. B., Siliciano R. F..( 2013;). A novel PCR assay for quantification of HIV-1 RNA. . J Virol 87: 6521–6525. [CrossRef] [PubMed]
    [Google Scholar]
  49. Swann R. E., Cowton V. M., Robinson M. W., Cole S. J., Barclay S. T., Mills P. R., Thomson E. C., McLauchlan J., Patel A. H..( 2016;). Broad anti-HCV antibody responses are associated with improved clinical disease parameters in chronic HCV infection. . J Virol 90: 4530–4543.[CrossRef]
    [Google Scholar]
  50. Tamura K., Nei M..( 1993;). Estimation of the number of nucleotide substitutions in the control region of mitochondrial DNA in humans and chimpanzees. . Mol Biol Evol 10: 512–526.[PubMed]
    [Google Scholar]
  51. Tamura K., Stecher G., Peterson D., Filipski A., Kumar S..( 2013;). mega6: molecular evolutionary genetics analysis version 6.0. . Mol Biol Evol 30: 2725–2729. [CrossRef] [PubMed]
    [Google Scholar]
  52. Thomas D. L., Astemborski J., Rai R. M., Anania F. A., Schaeffer M., Galai N., Nolt K., Nelson K. E., Strathdee S. A. et al.( 2000;). The natural history of hepatitis C virus infection: host, viral, and environmental factors. . JAMA 284: 450–456.[PubMed] [CrossRef]
    [Google Scholar]
  53. Timpe J. M., Stamataki Z., Jennings A., Hu K., Farquhar M. J., Harris H. J., Schwarz A., Desombere I., Roels G. L. et al.( 2008;). Hepatitis C virus cell-cell transmission in hepatoma cells in the presence of neutralizing antibodies. . Hepatology 47: 17–24. [CrossRef] [PubMed]
    [Google Scholar]
  54. Urbanowicz R. A., McClure C. P., Brown R. J., Tsoleridis T., Persson M. A., Krey T., Irving W. L., Ball J. K., Tarr A. W..( 2015;). A diverse panel of hepatitis C virus glycoproteins for use in vaccine research reveals extremes of monoclonal antibody neutralization resistance. . J Virol 90: 3288–3301. [CrossRef] [PubMed]
    [Google Scholar]
  55. Urbanowicz R. A., McClure C. P., King B., Mason C. P., Ball J. K., Tarr A. W..( 2016;). Novel functional hepatitis C virus glycoprotein isolates identified using an optimized viral pseudotype entry assay. . J Gen Virol 97: 2265–2279. [CrossRef] [PubMed]
    [Google Scholar]
  56. Vieyres G., Thomas X., Descamps V., Duverlie G., Patel A. H., Dubuisson J..( 2010;). Characterization of the envelope glycoproteins associated with infectious hepatitis C virus. . J Virol 84: 10159–10168. [CrossRef] [PubMed]
    [Google Scholar]
  57. Wasilewski L. N., El-Diwany R., Munshaw S., Snider A. E., Brady J. K., Osburn W. O., Ray S. C., Bailey J. R..( 2016;). A hepatitis C virus envelope polymorphism confers resistance to neutralization by polyclonal sera and broadly neutralizing monoclonal antibodies. . J Virol 90: 3773–3782. [CrossRef] [PubMed]
    [Google Scholar]
  58. Youn J. W., Park S. H., Lavillette D., Cosset F. L., Yang S. H., Lee C. G., Jin H. T., Kim C. M., Shata M. T. et al.( 2005;). Sustained E2 antibody response correlates with reduced peak viremia after hepatitis C virus infection in the chimpanzee. . Hepatology 42: 1429–1436. [CrossRef] [PubMed]
    [Google Scholar]
  59. Zhang J., Randall G., Higginbottom A., Monk P., Rice C. M., McKeating J. A..( 2004;). CD81 is required for hepatitis C virus glycoprotein-mediated viral infection. . J Virol 78: 1448–1455. [CrossRef] [PubMed]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/jgv.0.000608
Loading
/content/journal/jgv/10.1099/jgv.0.000608
Loading

Data & Media loading...

Supplementary File 1

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