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.

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2016-11-10
2020-04-02
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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 Med144:705–714 [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 Dis55: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 Invest125:437–447 [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 Dis212:914–923[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 Chem278:41624–41630 [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 Chem289:18904–18913 [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 Virol85:596–605 [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 A99:14416–14421 [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 Virol87:1385–1399 [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. Hepatology60:1551–1562 [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 A110:9505–9510 [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 A101:7270–7274 [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. Gastroenterology136:2377–2386 [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 Virol81:8072–8079 [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. Gastroenterology150:206–217 [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. Gastroenterology143:223–233 [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. Hepatology32:618–625 [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 A109:6205–6210 [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. Gastroenterology133:1614–1626 [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. Hepatology49:364–377 [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 Virol74:10407–10416 [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 Virol84:12048–12057 [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 Med368:1859–1861 [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 A100:7271–7276 [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 Virol83:12680–12691 [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 Virol86:7256–7267 [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 Virol82:6067–6072 [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 Virol83:6149–6160 [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 Pathog8: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 Virol87:37–51 [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 Virol88:10584–10597 [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 Med14:25–27 [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 A103:3805–3809 [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 A101:10149–10154 [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. Virology458–459:190–208 [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 Virol89:7758–7775 [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 Virol97:2187–2193 [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 Virol78:8496–8505 [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 A102:4560–4565 [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 Virol82:9647–9656 [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 Pathog8: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. Hepatology59:2140–2151 [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 A104:6025–6030 [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. Gastroenterology139:1355–1364 [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 Hepat16:621–632 [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 A105:997–1002 [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 Virol85:2891–2906 [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 Virol87:6521–6525 [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 Virol90:4530–4543[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 Evol10:512–526[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 Evol30:2725–2729 [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. JAMA284:450–456[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. Hepatology47:17–24 [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 Virol90:3288–3301 [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 Virol97:2265–2279 [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 Virol84:10159–10168 [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 Virol90:3773–3782 [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. Hepatology42:1429–1436 [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 Virol78:1448–1455 [CrossRef][PubMed]
    [Google Scholar]
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