Antigenic site changes in the rabies virus glycoprotein dictates functionality and neutralizing capability against divergent lyssaviruses Open Access

Abstract

Lyssavirus infection has a near 100 % case fatality rate following the onset of clinical disease, and current rabies vaccines confer protection against all reported phylogroup I lyssaviruses. However, there is little or no protection against more divergent lyssaviruses and so investigation into epitopes within the glycoprotein (G) that dictate a neutralizing response against divergent lyssaviruses is warranted. Importantly, the facilities required to work with these pathogens, including wild-type and mutated forms of different lyssaviruses, are scarcely available and, as such, this type of study is inherently difficult to perform. The relevance of proposed immunogenic antigenic sites within the lyssavirus glycoprotein was assessed by swapping sites between phylogroup-I and -II glycoproteins. Demonstrable intra- but limited inter-phylogroup cross-neutralization was observed. Pseudotype viruses (PTVs) presenting a phylogroup-I glycoprotein containing phylogroup-II antigenic sites (I, II III or IV) were neutralized by antibodies raised against phylogroup-II PTV with the site II (IIb, aa 34–42 and IIa, aa 198–200)-swapped PTVs being efficiently neutralized, whilst site IV-swapped PTV was poorly neutralized. Specific antibodies raised against PTV-containing antigenic site swaps between phylogroup-I and -II glycoproteins neutralized phylogroup-I PTVs efficiently, indicating an immunodominance of antigenic site II. Live lyssaviruses containing antigenic site-swapped glycoproteins were generated and indicated that specific residues within the lyssavirus glycoprotein dictate functionality and enable differential neutralizing antibody responses to lyssaviruses.

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2018-02-01
2024-03-29
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References

  1. Fooks AR, Banyard AC, Horton DL, Johnson N, McElhinney LM et al. Current status of rabies and prospects for elimination. Lancet 2014; 384:1389–1399 [View Article][PubMed]
    [Google Scholar]
  2. Blanton JD, Palmer D, Christian KA, Rupprecht CE. Rabies surveillance in the United States during 2007. J Am Vet Med Assoc 2008; 233:884–897 [View Article][PubMed]
    [Google Scholar]
  3. WHO WHO Expert Consultation on rabies. World Health Organ Tech Rep Ser 2005; 931:1–88[PubMed]
    [Google Scholar]
  4. WHO WHO Expert consultation on rabies: second report; 2013
  5. Hampson K, Coudeville L, Lembo T, Sambo M, Kieffer A et al. Estimating the global burden of endemic canine rabies. PLoS Negl Trop Dis 2015; 9:e0003709 [View Article][PubMed]
    [Google Scholar]
  6. Badrane H, Tordo N. Host switching in Lyssavirus history from the Chiroptera to the Carnivora orders. J Virol 2001; 75:8096–8104[PubMed] [Crossref]
    [Google Scholar]
  7. Banyard AC, Fooks AR. The impact of novel lyssavirus discovery. Micro Aust 2017; 38:18–21
    [Google Scholar]
  8. Evans JS, Horton DL, Easton AJ, Fooks AR, Banyard AC. Rabies virus vaccines: is there a need for a pan-lyssavirus vaccine?. Vaccine 2012; 30:7447–7454 [View Article][PubMed]
    [Google Scholar]
  9. Moore SM, Hanlon CA. Rabies-specific antibodies: measuring surrogates of protection against a fatal disease. PLoS Negl Trop Dis 2010; 4:e595 [View Article][PubMed]
    [Google Scholar]
  10. ICTV 2012; Official taxonomy: updates since the 8th report, 2009. www.talkictvonlineorg/files/proposals/taxonomy_proposals_vertebrate1/m/vert04/4068aspx [accessed 27.07.12 2012]
  11. Nadin-Davis S. Molecular epidemiology. In Jackson AC, Wunner W. (editors) Rabies London: Elsevier/Academic Press; 2007 pp. 341–381
    [Google Scholar]
  12. Horton DL, McElhinney LM, Marston DA, Wood JL, Russell CA et al. Quantifying antigenic relationships among the lyssaviruses. J Virol 2010; 84:11841–11848 [View Article][PubMed]
    [Google Scholar]
  13. Kuzmin IV, Niezgoda M, Franka R, Agwanda B, Markotter W et al. Possible emergence of West Caucasian bat virus in Africa. Emerg Infect Dis 2008; 14:1887–1889 [View Article][PubMed]
    [Google Scholar]
  14. Fooks A. The challenge of new and emerging lyssaviruses. Expert Rev Vaccines 2004; 3:333–336 [View Article][PubMed]
    [Google Scholar]
  15. Horton DL, Banyard AC, Marston DA, Wise E, Selden D et al. Antigenic and genetic characterization of a divergent African virus, Ikoma lyssavirus. J Gen Virol 2014; 95:1025–1032 [Crossref]
    [Google Scholar]
  16. Aréchiga Ceballos N, Vázquez Morón S, Berciano JM, Nicolás O, Aznar López C et al. Novel lyssavirus in bat, Spain. Emerg Infect Dis 2013; 19:793–795 [View Article][PubMed]
    [Google Scholar]
  17. Badrane H, Bahloul C, Perrin P, Tordo N. Evidence of two Lyssavirus phylogroups with distinct pathogenicity and immunogenicity. J Virol 2001; 75:3268–3276 [View Article][PubMed]
    [Google Scholar]
  18. Hanlon CA, Kuzmin IV, Blanton JD, Weldon WC, Manangan JS et al. Efficacy of rabies biologics against new lyssaviruses from Eurasia. Virus Res 2005; 111:44–54 [View Article][PubMed]
    [Google Scholar]
  19. Horton DL, Banyard AC, Marston DA, Wise E, Selden D et al. Antigenic and genetic characterization of a divergent African virus, Ikoma lyssavirus. J Gen Virol 2014; 95:1025–1032 [View Article][PubMed]
    [Google Scholar]
  20. Fekadu M, Shaddock JH, Sanderlin DW, Smith JS. Efficacy of rabies vaccines against Duvenhage virus isolated from European house bats (Eptesicus serotinus), classic rabies and rabies-related viruses. Vaccine 1988; 6:533–539[PubMed] [Crossref]
    [Google Scholar]
  21. Brookes SM, Parsons G, Johnson N, McElhinney LM, Fooks AR. Rabies human diploid cell vaccine elicits cross-neutralising and cross-protecting immune responses against European and Australian bat lyssaviruses. Vaccine 2005; 23:4101–4109 [View Article][PubMed]
    [Google Scholar]
  22. Brookes SM, Healy DM, Fooks AR. Ability of rabies vaccine strains to elicit cross-neutralising antibodies. Dev Biol 2006; 125:185–193[PubMed]
    [Google Scholar]
  23. Nolden T, Banyard AC, Finke S, Fooks AR, Hanke D et al. Comparative studies on the genetic, antigenic and pathogenic characteristics of Bokeloh bat lyssavirus. J Gen Virol 2014; 95:1647–1653 [View Article][PubMed]
    [Google Scholar]
  24. Gaudin Y, Ruigrok RW, Tuffereau C, Knossow M, Flamand A. Rabies virus glycoprotein is a trimer. Virology 1992; 187:627–632[PubMed] [Crossref]
    [Google Scholar]
  25. Lafon M, Wiktor TJ, Macfarlan RI. Antigenic sites on the CVS rabies virus glycoprotein: analysis with monoclonal antibodies. J Gen Virol 1983; 64:843–851 [View Article][PubMed]
    [Google Scholar]
  26. Benmansour A, Leblois H, Coulon P, Tuffereau C, Gaudin Y et al. Antigenicity of rabies virus glycoprotein. J Virol 1991; 65:4198–4203[PubMed]
    [Google Scholar]
  27. Prehaud C, Coulon P, Lafay F, Thiers C, Flamand A. Antigenic site II of the rabies virus glycoprotein: structure and role in viral virulence. J Virol 1988; 62:1–7[PubMed]
    [Google Scholar]
  28. Dietzschold B, Wunner WH, Wiktor TJ, Lopes AD, Lafon M et al. Characterization of an antigenic determinant of the glycoprotein that correlates with pathogenicity of rabies virus. Proc Natl Acad Sci USA 1983; 80:70–74 [View Article][PubMed]
    [Google Scholar]
  29. Seif I, Coulon P, Rollin PE, Flamand A. Rabies virulence: effect on pathogenicity and sequence characterization of rabies virus mutations affecting antigenic site III of the glycoprotein. J Virol 1985; 53:926–934[PubMed]
    [Google Scholar]
  30. Coulon P, Ternaux JP, Flamand A, Tuffereau C. An avirulent mutant of rabies virus is unable to infect motoneurons in vivo and in vitro. J Virol 1998; 72:273–278[PubMed]
    [Google Scholar]
  31. Bunschoten H, Gore M, Claassen IJ, Uytdehaag FG, Dietzschold B et al. Characterization of a new virus-neutralizing epitope that denotes a sequential determinant on the rabies virus glycoprotein. J Gen Virol 1989; 70:291–298 [View Article][PubMed]
    [Google Scholar]
  32. Ni Y, Tominaga Y, Honda Y, Morimoto K, Sakamoto S et al. Mapping and characterization of a sequential epitope on the rabies virus glycoprotein which is recognized by a neutralizing monoclonal antibody, RG719. Microbiol Immunol 1995; 39:693–702[PubMed] [Crossref]
    [Google Scholar]
  33. Luo TR, Minamoto N, Ito H, Goto H, Hiraga S et al. A virus-neutralizing epitope on the glycoprotein of rabies virus that contains Trp251 is a linear epitope. Virus Res 1997; 51:35–41[PubMed] [Crossref]
    [Google Scholar]
  34. Roche S, Rey FA, Gaudin Y, Bressanelli S. Structure of the prefusion form of the vesicular stomatitis virus glycoprotein G. Science 2007; 315:843–848 [View Article][PubMed]
    [Google Scholar]
  35. Roche S, Bressanelli S, Rey FA, Gaudin Y. Crystal structure of the low-pH form of the vesicular stomatitis virus glycoprotein G. Science 2006; 313:187–191 [View Article][PubMed]
    [Google Scholar]
  36. de Benedictis P, Minola A, Rota Nodari E, Aiello R, Zecchin B et al. Development of broad-spectrum human monoclonal antibodies for rabies post-exposure prophylaxis. EMBO Mol Med 2016; 8:407–421 [View Article][PubMed]
    [Google Scholar]
  37. Morimoto K, Foley HD, McGettigan JP, Schnell MJ, Dietzschold B. Reinvestigation of the role of the rabies virus glycoprotein in viral pathogenesis using a reverse genetics approach. J Neurovirol 2000; 6:373–381[PubMed] [Crossref]
    [Google Scholar]
  38. Marston DA, McElhinney LM, Banyard AC, Horton DL, Núñez A et al. Interspecies protein substitution to investigate the role of the lyssavirus glycoprotein. J Gen Virol 2013; 94:284–292 [View Article][PubMed]
    [Google Scholar]
  39. Fernando BG, Yersin CT, José CB, Paola ZS. Predicted 3D model of the rabies virus glycoprotein trimer. Biomed Res Int 2016; 2016:1–11 [View Article][PubMed]
    [Google Scholar]
  40. Corti D, Voss J, Gamblin SJ, Codoni G, Macagno A et al. A neutralizing antibody selected from plasma cells that binds to group 1 and group 2 influenza A hemagglutinins. Science 2011; 333:850–856 [View Article][PubMed]
    [Google Scholar]
  41. Wright E, Hayman DT, Vaughan A, Temperton NJ, Wood JL et al. Virus neutralising activity of African fruit bat (Eidolon helvum) sera against emerging lyssaviruses. Virology 2010; 408:183–189 [View Article][PubMed]
    [Google Scholar]
  42. Nightingale SJ, Hollis RP, Pepper KA, Petersen D, Yu XJ et al. Transient gene expression by nonintegrating lentiviral vectors. Mol Ther 2006; 13:1121–1132 [View Article][PubMed]
    [Google Scholar]
  43. Freuling CM, Binger T, Beer M, Adu-Sarkodie Y, Schatz J et al. Lagos bat virus transmission in an Eidolon helvum bat colony, Ghana. Virus Res 2015; 210:42–45 [View Article][PubMed]
    [Google Scholar]
  44. Ghildyal R, Li D, Peroulis I, Shields B, Bardin PG et al. Interaction between the respiratory syncytial virus G glycoprotein cytoplasmic domain and the matrix protein. J Gen Virol 2005; 86:1879–1884 [View Article][PubMed]
    [Google Scholar]
  45. Enami M, Enami K. Influenza virus hemagglutinin and neuraminidase glycoproteins stimulate the membrane association of the matrix protein. J Virol 1996; 70:6653–6657[PubMed]
    [Google Scholar]
  46. Lyles DS, McKenzie M, Parce JW. Subunit interactions of vesicular stomatitis virus envelope glycoprotein stabilized by binding to viral matrix protein. J Virol 1992; 66:349–358[PubMed]
    [Google Scholar]
  47. Mebatsion T, Weiland F, Conzelmann KK. Matrix protein of rabies virus is responsible for the assembly and budding of bullet-shaped particles and interacts with the transmembrane spike glycoprotein G. J Virol 1999; 73:242–250[PubMed]
    [Google Scholar]
  48. Genz B, Nolden T, Negatsch A, Teifke JP, Conzelmann KK et al. Chimeric rabies viruses for trans-species comparison of lyssavirus glycoprotein ectodomain functions in virus replication and pathogenesis. Berl Munch Tierarztl Wochenschr 2012; 125:219–227[PubMed]
    [Google Scholar]
  49. Costa LJ, Andrade FA, Uieda W, Martorelli LF, Kataoka AP et al. Serological investigation of rabies virus neutralizing antibodies in bats captured in the eastern Brazilian Amazon. Trans R Soc Trop Med Hyg 2013; 107:684–689 [View Article][PubMed]
    [Google Scholar]
  50. Wright E, Temperton NJ, Marston DA, McElhinney LM, Fooks AR et al. Investigating antibody neutralization of lyssaviruses using lentiviral pseudotypes: a cross-species comparison. J Gen Virol 2008; 89:2204–2213 [View Article][PubMed]
    [Google Scholar]
  51. WHO Laboratory Techniques in Rabies Geneva: World Health Organisation; 1996
    [Google Scholar]
  52. Faber M, Pulmanausahakul R, Nagao K, Prosniak M, Rice AB et al. Identification of viral genomic elements responsible for rabies virus neuroinvasiveness. Proc Natl Acad Sci USA 2004; 101:16328–16332 [View Article][PubMed]
    [Google Scholar]
  53. Healy DM, Brookes SM, Banyard AC, Núñez A, Cosby SL et al. Pathobiology of rabies virus and the European bat lyssaviruses in experimentally infected mice. Virus Res 2013; 172:46–53 [View Article][PubMed]
    [Google Scholar]
  54. Smith DJ, Lapedes AS, de Jong JC, Bestebroer TM, Rimmelzwaan GF et al. Mapping the antigenic and genetic evolution of influenza virus. Science 2004; 305:371–376 [View Article][PubMed]
    [Google Scholar]
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