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Volume 95, Issue 5

Antigenic and genetic characterization of a divergent African virus, Ikoma lyssavirus Open Access

Abstract

In 2009, a novel lyssavirus (subsequently named Ikoma lyssavirus, IKOV) was detected in the brain of an African civet () with clinical rabies in the Serengeti National Park of Tanzania. The degree of nucleotide divergence between the genome of IKOV and those of other lyssaviruses predicted antigenic distinction from, and lack of protection provided by, available rabies vaccines. In addition, the index case was considered likely to be an incidental spillover event, and therefore the true reservoir of IKOV remained to be identified. The advent of sensitive molecular techniques has led to a rapid increase in the discovery of novel viruses. Detecting viral sequence alone, however, only allows for prediction of phenotypic characteristics and not their measurement. In the present study we describe the and characterization of IKOV, demonstrating that it is (1) pathogenic by peripheral inoculation in an animal model, (2) antigenically distinct from current rabies vaccine strains and (3) poorly neutralized by sera from humans and animals immunized against rabies. In a laboratory mouse model, no protection was elicited by a licensed rabies vaccine. We also investigated the role of bats as reservoirs of IKOV. We found no evidence for infection among 483 individuals of at least 13 bat species sampled across sites in the Serengeti and Southern Kenya.

  • Received:
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© 2014 Crown Copyright
  • This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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2014-05-01
2024-04-19
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References

  1. Anon 2009 Current WHO Guide for Rabies Pre and Post-exposure Prophylaxis in Humans Geneva: World Health Organisation;
     [Google Scholar]
  2. Aréchiga Ceballos N., Vázquez Morón S., Berciano J. M., Nicolás O., Aznar López C., Juste J., Rodríguez Nevado C., Aguilar Setién A., Echevarría J. E. 2013; Novel lyssavirus in bat, Spain. Emerg Infect Dis 19:793–795 [View Article][PubMed]
     [Google Scholar]
  3. Aubert M. 1996; Methods for the calculation of titres. In Laboratory Techniques in Rabies pp. 445–459 Edited by Meslin F. X., Kaplan M. M., Koprowski H. Geneva: World Health Organisation;
     [Google Scholar]
  4. Badrane H., Bahloul C., Perrin P., Tordo N. 2001; Evidence of two Lyssavirus phylogroups with distinct pathogenicity and immunogenicity. J Virol 75:3268–3276 [View Article][PubMed]
     [Google Scholar]
  5. Banyard A. C., Hayman D., Johnson N., McElhinney L., Fooks A. R. 2011; Bats and lyssaviruses. Adv Virus Res 79:239–289 [View Article][PubMed]
     [Google Scholar]
  6. Banyard A. C., Horton D. L., Freuling C., Müller T., Fooks A. R. 2013; Control and prevention of canine rabies: the need for building laboratory-based surveillance capacity. Antiviral Res 98:357–364 [View Article][PubMed]
     [Google Scholar]
  7. Bexfield N., Kellam P. 2011; Metagenomics and the molecular identification of novel viruses. Vet J 190:191–198 [View Article][PubMed]
     [Google Scholar]
  8. Bodewes R., van der Giessen J., Haagmans B. L., Osterhaus A. D., Smits S. L. 2013; Identification of multiple novel viruses, including a parvovirus and a hepevirus, in feces of red foxes. J Virol 87:7758–7764 [View Article][PubMed]
     [Google Scholar]
  9. Brookes S. M., Parsons G., Johnson N., McElhinney L. M., Fooks A. R. 2005a; Rabies human diploid cell vaccine elicits cross-neutralising and cross-protecting immune responses against European and Australian bat lyssaviruses. Vaccine 23:4101–4109 [View Article][PubMed]
     [Google Scholar]
  10. Brookes S. M., Aegerter J. N., Smith G. C., Healy D. M., Jolliffe T. A., Swift S. M., Mackie I. J., Pritchard J. S., Racey P. A. other authors 2005b; European bat lyssavirus in Scottish bats. Emerg Infect Dis 11:572–578 [View Article][PubMed]
     [Google Scholar]
  11. Brookes S. M., Healy D. M., Fooks A. R. 2006; Ability of rabies vaccine strains to elicit cross-neutralising antibodies. Dev Biol (Basel) 125:185–193[PubMed]
     [Google Scholar]
  12. Cleaveland S., Dye C. 1995; Maintenance of a microparasite infecting several host species: rabies in the Serengeti. Parasitology 111:SupplS33–S47 [View Article][PubMed]
     [Google Scholar]
  13. Cliquet F., Aubert M., Sagné L. 1998; Development of a fluorescent antibody virus neutralisation test (FAVN test) for the quantitation of rabies-neutralising antibody. J Immunol Methods 212:79–87 [View Article][PubMed]
     [Google Scholar]
  14. Dean D. J., Abelseth M. K., Atanasiu P. 1996; The fluorescent antibody test. In Laboratory Techniques in Rabies pp. 88–93 Edited by Meslin F. X., Kaplan M. M., Koprowski H. Geneva: World Health Organisation;
     [Google Scholar]
  15. Dietzgen R. G., Calisher C. H., Kurath G., Kuzmin I. V., Rodriguez L. L., Stone D. M., Tesh R. B., Tordo N., Walker P. J. other authors 2011; Rhabdoviridae. In Virus Taxonomy: Ninth Report of the International Committee on Taxonomy of Viruses Edited by Andrew M. J. A., King M. Q., Carstens E. B., Lefkowitz E. J. Oxford: Elsevier;
     [Google Scholar]
  16. Estes R. D. 1992; Chapter 19: Family Viverridae. In The Behavior Guide to African Mammals, 1st edn. California: University of California Press;
     [Google Scholar]
  17. Evans J. S., Horton D. L., Easton A. J., Fooks A. R., Banyard A. C. 2012; Rabies virus vaccines: is there a need for a pan-lyssavirus vaccine?. Vaccine 30:7447–7454 [View Article][PubMed]
     [Google Scholar]
  18. Fooks A. 2004; The challenge of new and emerging lyssaviruses. Expert Rev Vaccines 3:333–336 [View Article][PubMed]
     [Google Scholar]
  19. Ge X., Li Y., Yang X., Zhang H., Zhou P., Zhang Y., Shi Z. 2012; Metagenomic analysis of viruses from bat fecal samples reveals many novel viruses in insectivorous bats in China. J Virol 86:4620–4630 [View Article][PubMed]
     [Google Scholar]
  20. Hanlon C. A., Kuzmin I. V., Blanton J. D., Weldon W. C., Manangan J. S., Rupprecht C. E. 2005; Efficacy of rabies biologics against new lyssaviruses from Eurasia. Virus Res 111:44–54 [View Article][PubMed]
     [Google Scholar]
  21. Harris S. L., Aegerter J. N., Brookes S. M., McElhinney L. M., Jones G., Smith G. C., Fooks A. R. 2009; Targeted surveillance for European bat lyssaviruses in English bats (2003–06). J Wildl Dis 45:1030–1041, 1041 [View Article][PubMed]
     [Google Scholar]
  22. Hayman D. T., Banyard A. C., Wakeley P. R., Harkess G., Marston D., Wood J. L., Cunningham A. A., Fooks A. R. 2011; A universal real-time assay for the detection of Lyssaviruses. J Virol Methods 177:87–93 [View Article][PubMed]
     [Google Scholar]
  23. Hayman D. T., Fooks A. R., Rowcliffe J. M., McCrea R., Restif O., Baker K. S., Horton D. L., Suu-Ire R., Cunningham A. A., Wood J. L. N. 2012; Endemic Lagos bat virus infection in Eidolon helvum . Epidemiol Infect 140:2163–2171 [View Article][PubMed]
     [Google Scholar]
  24. Healy D. M., Brookes S. M., Banyard A. C., Núñez A., Cosby S. L., Fooks A. R. 2013; Pathobiology of rabies virus and the European bat lyssaviruses in experimentally infected mice. Virus Res 172:46–53 [View Article][PubMed]
     [Google Scholar]
  25. Hicks D. J., Nuñez A., Healy D. M., Brookes S. M., Johnson N., Fooks A. R. 2009; Comparative pathological study of the murine brain after experimental infection with classical rabies virus and European bat lyssaviruses. J Comp Pathol 140:113–126 [View Article][PubMed]
     [Google Scholar]
  26. Horton D. L., McElhinney L. M., Marston D. A., Wood J. L., Russell C. A., Lewis N., Kuzmin I. V., Fouchier R. A., Osterhaus A. D. other authors 2010; Quantifying antigenic relationships among the lyssaviruses. J Virol 84:11841–11848 [View Article][PubMed]
     [Google Scholar]
  27. IUCN 2013; IUCN Red List of Threatened Species. Version 2013.1.
    [Google Scholar]
  28. Johnson N., Vos A., Freuling C., Tordo N., Fooks A. R., Müller T. 2010; Human rabies due to lyssavirus infection of bat origin. Vet Microbiol 142:151–159 [View Article][PubMed]
     [Google Scholar]
  29. Kgaladi J., Nel L. H., Markotter W. 2013; Comparison of pathogenic domains of rabies and African rabies-related lyssaviruses and pathogenicity observed in mice. Onderstepoort J Vet Res 80:511 [View Article][PubMed]
     [Google Scholar]
  30. Koraka P., Martina B. E., Roose J. M., van Thiel P. P., van Amerongen G., Kuiken T., Osterhaus A. D. 2012; In vitro and in vivo isolation and characterization of Duvenhage virus. PLoS Pathog 8:e1002682 [View Article][PubMed]
     [Google Scholar]
  31. Kuzmin I. V., Hughes G. J., Botvinkin A. D., Orciari L. A., Rupprecht C. E. 2005; Phylogenetic relationships of Irkut and West Caucasian bat viruses within the Lyssavirus genus and suggested quantitative criteria based on the N gene sequence for lyssavirus genotype definition. Virus Res 111:28–43 [View Article][PubMed]
     [Google Scholar]
  32. Kuzmin I. V., Niezgoda M., Franka R., Agwanda B., Markotter W., Beagley J. C., Urazova O. Y., Breiman R. F., Rupprecht C. E. 2008a; Possible emergence of West Caucasian bat virus in Africa. Emerg Infect Dis 14:1887–1889 [View Article][PubMed]
     [Google Scholar]
  33. Kuzmin I. V., Niezgoda M., Franka R., Agwanda B., Markotter W., Beagley J. C., Urazova O. Y., Breiman R. F., Rupprecht C. E. 2008b; Lagos bat virus in Kenya. J Clin Microbiol 46:1451–1461 [View Article][PubMed]
     [Google Scholar]
  34. Kuzmin I. V., Mayer A. E., Niezgoda M., Markotter W., Agwanda B., Breiman R. F., Rupprecht C. E. 2010; Shimoni bat virus, a new representative of the Lyssavirus genus. Virus Res 149:197–210 [View Article][PubMed]
     [Google Scholar]
  35. Lembo T., Hampson K., Haydon D. T., Craft M., Dobson A., Dushoff J., Ernest E., Hoare R., Kaare M. other authors 2008; Exploring reservoir dynamics: a case study of rabies in the Serengeti ecosystem. J Appl Ecol 45:1246–1257 [View Article][PubMed]
     [Google Scholar]
  36. Li L., Shan T., Wang C., Côté C., Kolman J., Onions D., Gulland F. M., Delwart E. 2011; The fecal viral flora of California sea lions. J Virol 85:9909–9917 [View Article][PubMed]
     [Google Scholar]
  37. Lipkin W. I., Firth C. 2013; Viral surveillance and discovery. Curr Opin Virol 3:199–204 [View Article][PubMed]
     [Google Scholar]
  38. Lodmell D. L., Smith J. S., Esposito J. J., Ewalt L. C. 1995; Cross-protection of mice against a global spectrum of rabies virus variants. J Virol 69:4957–4962[PubMed]
     [Google Scholar]
  39. Malerczyk C., Selhorst T., Tordo N., Moore S., Müller T. 2009; Antibodies induced by vaccination with purified chick embryo cell culture vaccine (PCECV) cross-neutralize non-classical bat lyssavirus strains. Vaccine 27:5320–5325 [View Article][PubMed]
     [Google Scholar]
  40. Markotter W., Van Eeden C., Kuzmin I. V., Rupprecht C. E., Paweska J. T., Swanepoel R., Fooks A. R., Sabeta C. T., Cliquet F., Nel L. H. 2008; Epidemiology and pathogenicity of African bat lyssaviruses. Dev Biol (Basel) 131:317–325[PubMed]
     [Google Scholar]
  41. Marston D. A., Horton D. L., Ngeleja C., Hampson K., McElhinney L. M., Banyard A. C., Haydon D., Cleaveland S., Rupprecht C. E. other authors 2012a; Ikoma lyssavirus, highly divergent novel lyssavirus in an African civet. Emerg Infect Dis 18:664–667 [View Article][PubMed]
     [Google Scholar]
  42. Marston D. A., Ellis R. J., Horton D. L., Kuzmin I. V., Wise E. L., McElhinney L. M., Banyard A. C., Ngeleja C., Keyyu J. other authors 2012b; Complete genome sequence of Ikoma lyssavirus. J Virol 86:10242–10243 [View Article][PubMed]
     [Google Scholar]
  43. Phan T. G., Kapusinszky B., Wang C., Rose R. K., Lipton H. L., Delwart E. L. 2011; The fecal viral flora of wild rodents. PLoS Pathog 7:e1002218 [View Article][PubMed]
     [Google Scholar]
  44. Robardet E., Demerson J. M., Andrieu S., Cliquet F. 2012; First European interlaboratory comparison of tetracycline and age determination with red fox teeth following oral rabies vaccination programs. J Wildl Dis 48:858–868 [View Article][PubMed]
     [Google Scholar]
  45. Sabeta C. T., Shumba W., Mohale D. K., Miyen J. M., Wandeler A. I., Nel L. H. 2008; Mongoose rabies and the African civet in Zimbabwe. Vet Rec 163:580 [View Article][PubMed]
     [Google Scholar]
  46. Turmelle A. S., Allen L. C., Jackson F. R., Kunz T. H., Rupprecht C. E., McCracken G. F. 2009; Ecology of rabies virus exposure in colonies of Brazilian free-tailed bats (Tadarida brasiliensis) at natural and man-made roosts in Texas. Vector Borne Zoonotic Dis 10:165–175[PubMed] [CrossRef]
     [Google Scholar]
  47. van den Brand J. M., van Leeuwen M., Schapendonk C. M., Simon J. H., Haagmans B. L., Osterhaus A. D., Smits S. L. 2012; Metagenomic analysis of the viral flora of pine marten and European badger feces. J Virol 86:2360–2365 [View Article][PubMed]
     [Google Scholar]
  48. Wilbur L. A., Aubert M. 1996; NIH test for potency. In Laboratory Techniques in Rabies, 4th edn. pp. 360–368 Edited by Meslin F. X., Kaplan M. M., Koprowski H. Geneva: World Health Organisation;
     [Google Scholar]
  49. Wright E., McNabb S., Goddard T., Horton D. L., Lembo T., Nel L. H., Weiss R. A., Cleaveland S., Fooks A. R. 2009; A robust lentiviral pseudotype neutralisation assay for in-field serosurveillance of rabies and lyssaviruses in Africa. Vaccine 27:7178–7186 [View Article][PubMed]
     [Google Scholar]
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Antigenic and genetic characterization of a divergent African virus, Ikoma lyssavirus
J. Gen. Virol. 95, 1025 (2014); https://doi.org/10.1099/vir.0.061952-0
/content/journal/jgv/10.1099/vir.0.061952-0
/content/journal/jgv/10.1099/vir.0.061952-0
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