1887

Journal of General Virology header logo

Volume 95, Issue 6

Evaluation of a mouse model for the West Nile virus group for the purpose of determining viral pathotypes Free

Abstract

(WNV; family ; genus ) group members are an important cause of viral meningoencephalitis in some areas of the world. They exhibit marked variation in pathogenicity, with some viral lineages (such as those from North America) causing high prevalence of severe neurological disease, whilst others (such as Australian Kunjin virus) rarely cause disease. The aim of this study was to characterize WNV disease in a mouse model and to elucidate the pathogenetic features that distinguish disease variation. Tenfold dilutions of five WNV strains (New York 1999, MRM16 and three horse isolates of WNV-Kunjin: Boort and two isolates from the 2011 Australian outbreak) were inoculated into mice by the intraperitoneal route. All isolates induced meningoencephalitis in different proportions of infected mice. WNV was the most pathogenic, the three horse isolates were of intermediate pathogenicity and WNV was the least, causing mostly asymptomatic disease with seroconversion. Infectivity, but not pathogenicity, was related to challenge dose. Using cluster analysis of the recorded clinical signs, histopathological lesions and antigen distribution scores, the cases could be classified into groups corresponding to disease severity. Metrics that were important in determining pathotype included neurological signs (paralysis and seizures), meningoencephalitis, brain antigen scores and replication in extra-neural tissues. Whereas all mice infected with WNV had extra-neural antigen, those infected with the WNV-Kunjin viruses only occasionally had antigen outside the nervous system. We conclude that the mouse model could be a useful tool for the assessment of pathotype for WNVs.

  • Received:
  • Accepted:
  • Published Online:
© 2014 CSIRO
Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.063537-0
2014-06-01
2024-04-20
Loading full text...

Full text loading...

/deliver/fulltext/jgv/95/6/1221.html?itemId=/content/journal/jgv/10.1099/vir.0.063537-0&mimeType=html&fmt=ahah

References

  1. Adams S. C., Broom A. K., Sammels L. M., Hartnett A. C., Howard M. J., Coelen R. J., Mackenzie J. S., Hall R. A. 1995; Glycosylation and antigenic variation among Kunjin virus isolates. Virology 206:49–56 [View Article][PubMed]
     [Google Scholar]
  2. APHIS 2013 2012 Summary of the West Nile Virus Equine Cases in the United States US Department of Agricuture, Animal and Plant Health Inspection Service, Veterinary Services Centers for Epidemiology and Animal Health, National Surveillance Unit; http://www.aphis.usda.gov/vs/nahss/equine/wnv/2012_equine_west_nile_virus_final.pdf
     [Google Scholar]
  3. Armah H. B., Wang G., Omalu B. I., Tesh R. B., Gyure K. A., Chute D. J., Smith R. D., Dulai P., Vinters H. V.other authors 2007; Systemic distribution of West Nile virus infection: postmortem immunohistochemical study of six cases. Brain Pathol 17:354–362 [View Article][PubMed]
     [Google Scholar]
  4. Audsley M., Edmonds J., Liu W., Mokhonov V., Mokhonova E., Melian E. B., Prow N., Hall R. A., Khromykh A. A. 2011; Virulence determinants between New York 99 and Kunjin strains of West Nile virus. Virology 414:63–73 [View Article][PubMed]
     [Google Scholar]
  5. Badman R. T., Campbell J., Aldred J. 1984; Arbovirus infection of horses – Victoria 1984. Commun Dis Intell 17:5–6
     [Google Scholar]
  6. Bardina S. V., Lim J. K. 2012; The role of chemokines in the pathogenesis of neurotropic flaviviruses. Immunol Res 54:121–132 [View Article][PubMed]
     [Google Scholar]
  7. Beasley D. W. C., Davis C. T., Whiteman M., Granwehr B., Kinney R. M., Barrett A. D. T. 2004; Molecular determinants of virulence of West Nile virus in North America. Arch VirolSuppl 1835–41[PubMed]
     [Google Scholar]
  8. Boyle D. B., Dickerman R. W., Marshall I. D. 1983; Primary viraemia responses of herons to experimental infection with Murray Valley encephalitis, Kunjin and Japanese encephalitis viruses. Aust J Exp Biol Med Sci 61:655–664 [View Article][PubMed]
     [Google Scholar]
  9. CDC 2010; Surveillance for Human West Nile Virus Disease – United States, 1999–2008. MMWR Morb Mortal Wkly Rep 59:SS–2 [View Article][PubMed]
     [Google Scholar]
  10. Clark D. C., Lobigs M., Lee E., Howard M. J., Clark K., Blitvich B. J., Hall R. A. 2007; In situ reactions of monoclonal antibodies with a viable mutant of Murray Valley encephalitis virus reveal an absence of dimeric NS1 protein. J Gen Virol 88:1175–1183 [View Article][PubMed]
     [Google Scholar]
  11. Cordova S. P., Smith D. W., Broom A. K., Lindsay M. D., Dowse G. K., Beers M. Y. 2000; Murray Valley encephalitis in Western Australia in 2000, with evidence of southerly spread. Commun Dis Intell 24:368–372[PubMed]
     [Google Scholar]
  12. Daffis S., Lazear H. M., Liu W. J., Audsley M., Engle M., Khromykh A. A., Diamond M. S. 2011; The naturally attenuated Kunjin strain of West Nile virus shows enhanced sensitivity to the host type I interferon response. J Virol 85:5664–5668 [View Article][PubMed]
     [Google Scholar]
  13. Diamond M. S. 2009; Virus and host determinants of West Nile virus pathogenesis. PLoS Pathog 5:e1000452 [View Article][PubMed]
     [Google Scholar]
  14. Diamond M. S., Sitati E. M., Friend L. D., Higgs S., Shrestha B., Engle M. 2003; A critical role for induced IgM in the protection against West Nile virus infection. J Exp Med 198:1853–1862 [View Article][PubMed]
     [Google Scholar]
  15. Doherty R. L., Carley J. G., MacKerras M. J., Marks E. N. 1963; Studies of arthropod-borne virus infections in Queensland. III. Isolation and characterization of virus strains from wild-caught mosquitoes in North Queensland. Aust J Exp Biol 41:17–39 [View Article][PubMed]
     [Google Scholar]
  16. Donadieu E., Lowenski S., Servely J. L., Laloy E., Lilin T., Nowotny N., Richardson J., Zientara S., Lecollinet S., Coulpier M. 2013; Comparison of the neuropathology induced by two West Nile virus strains. PLoS ONE 8:e84473 [View Article][PubMed]
     [Google Scholar]
  17. Eidson M., Kramer L., Stone W., Hagiwara Y., Schmit K.New York State West Nile Virus Avian Surveillance Team 2001; Dead bird surveillance as an early warning system for West Nile virus. Emerg Infect Dis 7:631–635 [View Article][PubMed]
     [Google Scholar]
  18. Frost M. J., Zhang J., Edmonds J. H., Prow N. A., Gu X., Davis R., Hornitzky C., Arzey K. E., Finlaison D.other authors 2012; Characterization of virulent West Nile virus Kunjin strain, Australia, 2011. Emerg Infect Dis 18:792–800 [View Article][PubMed]
     [Google Scholar]
  19. Gray T. J., Burrow J. N., Markey P. G., Whelan P. I., Jackson J., Smith D. W., Currie B. J. 2011; West Nile Virus (Kunjin subtype) disease in the northern territory of Australia – a case of encephalitis and review of all reported cases. Am J Trop Med Hyg 85:952–956 [View Article][PubMed]
     [Google Scholar]
  20. Gray T. J., Burrow J. N., Markey P. G., Whelan P. I., Jackson J., Smith D. W., Currie B. J. 2012; West Nile Virus (Kunjin subtype) disease in the northern territory of Australia – a case of encephalitis and review of all reported cases [Erratum]. Am J Trop Med Hyg 86:181 [View Article]
     [Google Scholar]
  21. Guarner J., Shieh W. J., Hunter S., Paddock C. D., Morken T., Campbell G. L., Marfin A. A., Zaki S. R. 2004; Clinicopathologic study and laboratory diagnosis of 23 cases with West Nile virus encephalomyelitis. Hum Pathol 35:983–990 [View Article][PubMed]
     [Google Scholar]
  22. Hall R. A., Broom A. K., Smith D. W., Mackenzie J. S. 2002; The ecology and epidemiology of Kunjin virus. In Japanese Encephalitis and West Nile Viruses pp. 253–269 Edited by Mackenzie J. S., Barrett A. D. T., Deubel V. Berlin: Springer; [View Article]
     [Google Scholar]
  23. Hamilton M. A., Russo R. C., Thurston R. V. 1977; Trimmed Spearman–Karber method for estimating median lethal concentrations in toxicity bioassays. Environ Sci Technol 11:714–719 [View Article]
     [Google Scholar]
  24. Hayes E. B., Gubler D. J. 2006; West Nile virus: epidemiology and clinical features of an emerging epidemic in the United States. Annu Rev Med 57:181–194 [View Article][PubMed]
     [Google Scholar]
  25. Hayes E. B., Komar N., Nasci R. S., Montgomery S. P., O’Leary D. R., Campbell G. L. 2005a; Epidemiology and transmission dynamics of West Nile virus disease. Emerg Infect Dis 11:1167–1173 [View Article][PubMed]
     [Google Scholar]
  26. Hayes E. B., Sejvar J. J., Zaki S. R., Lanciotti R. S., Bode A. V., Campbell G. L. 2005b; Virology, pathology, and clinical manifestations of West Nile virus disease. Emerg Infect Dis 11:1174–1179 [View Article][PubMed]
     [Google Scholar]
  27. Huang C. H., Wong C. 1963; Relation of peripheral multiplication of Japanese B encephalitis virus to the pathogenesis of infection in mice. Acta Virol 7:322–330
     [Google Scholar]
  28. Keller B. C., Fredericksen B. L., Samuel M. A., Mock R. E., Mason P. W., Diamond M. S., Gale M. Jr 2006; Resistance to alpha/beta interferon is a determinant of West Nile virus replication fitness and virulence. J Virol 80:9424–9434 [View Article][PubMed]
     [Google Scholar]
  29. Kimura T., Sasaki M., Okumura M., Kim E., Sawa H. 2010; Flavivirus encephalitis: pathological aspects of mouse and other animal models. Vet Pathol 47:806–818 [View Article][PubMed]
     [Google Scholar]
  30. King N. J. C., Getts D. R., Getts M. T., Rana S., Shrestha B., Kesson A. M. 2007; Immunopathology of flavivirus infections. Immunol Cell Biol 85:33–42 [View Article][PubMed]
     [Google Scholar]
  31. Lanciotti R. S., Roehrig J. T., Deubel V., Smith J., Parker M., Steele K., Crise B., Volpe K. E., Crabtree M. B.other authors 1999; Origin of the West Nile virus responsible for an outbreak of encephalitis in the northeastern United States. Science 286:2333–2337 [View Article][PubMed]
     [Google Scholar]
  32. Lim S. M., Koraka P., Osterhaus A. D. M. E., Martina B. E. E. 2011; West Nile virus: immunity and pathogenesis. Viruses 3:811–828 [View Article][PubMed]
     [Google Scholar]
  33. Liu W. J., Wang X. J., Mokhonov V. V., Shi P. Y., Randall R., Khromykh A. A. 2005; Inhibition of interferon signaling by the New York 99 strain and Kunjin subtype of West Nile virus involves blockage of STAT1 and STAT2 activation by nonstructural proteins. J Virol 79:1934–1942 [View Article][PubMed]
     [Google Scholar]
  34. Liu W. J., Wang X. J., Clark D. C., Lobigs M., Hall R. A., Khromykh A. A. 2006; A single amino acid substitution in the West Nile virus nonstructural protein NS2A disables its ability to inhibit alpha/beta interferon induction and attenuates virus virulence in mice. J Virol 80:2396–2404 [View Article][PubMed]
     [Google Scholar]
  35. Mackenzie J. S., Smith D. W., Broom A. K., Bucens M. R. 1993; Australian encephalitis in Western Australia, 1978–1991. Med J Aust 158:591–595[PubMed]
     [Google Scholar]
  36. Malkova D., Frankova V. 1959; The lymphatic system in the development of experimental tick-borne encephalitis in mice. Acta Virol 3:210–214[PubMed]
     [Google Scholar]
  37. Mann R. A., Fegan M., O’Riley K., Motha J., Warner S. 2013; Molecular characterization and phylogenetic analysis of Murray Valley encephalitis virus and West Nile virus (Kunjin subtype) from an arbovirus disease outbreak in horses in Victoria, Australia, in 2011. J Vet Diagn Invest 25:35–44 [View Article][PubMed]
     [Google Scholar]
  38. May F. J., Davis C. T., Tesh R. B., Barrett A. D. T. 2011; Phylogeography of West Nile virus: from the cradle of evolution in Africa to Eurasia, Australia, and the Americas. J Virol 85:2964–2974 [View Article][PubMed]
     [Google Scholar]
  39. Mostashari F., Bunning M. L., Kitsutani P. T., Singer D. A., Nash D., Cooper M. J., Katz N., Liljebjelke K. A., Biggerstaff B. J.other authors 2001; Epidemic West Nile encephalitis, New York, 1999: results of a household-based seroepidemiological survey. Lancet 358:261–264 [View Article][PubMed]
     [Google Scholar]
  40. O’Leary D. R., Marfin A. A., Montgomery S. P., Kipp A. M., Lehman J. A., Biggerstaff B. J., Elko V. L., Collins P. D., Jones J. E., Campbell G. L. 2004; The epidemic of West Nile virus in the United States, 2002. Vector Borne Zoonotic Dis 4:61–70 [View Article][PubMed]
     [Google Scholar]
  41. Ostlund E. N., Crom R. L., Pedersen D. D., Johnson D. J., Williams W. O., Schmitt B. J. 2001; Equine West Nile encephalitis, United States. Emerg Infect Dis 7:665–669 [View Article][PubMed]
     [Google Scholar]
  42. Phillips D. A., Aaskov J. G., Atkin C., Wiemers M. A. 1992; Isolation of Kunjin virus from a patient with a naturally acquired infection. Med J Aust 157:190–191[PubMed]
     [Google Scholar]
  43. Roche S. E., Wicks R., Garner M. G., East I. J., Paskin R., Moloney B. J., Carr M., Kirkland P. 2013; Descriptive overview of the 2011 epidemic of arboviral disease in horses in Australia. Aust Vet J 91:5–13 [View Article][PubMed]
     [Google Scholar]
  44. Samuel M. A., Diamond M. S. 2005; Alpha/beta interferon protects against lethal West Nile virus infection by restricting cellular tropism and enhancing neuronal survival. J Virol 79:13350–13361 [View Article][PubMed]
     [Google Scholar]
  45. Samuel M. A., Whitby K., Keller B. C., Marri A., Barchet W., Williams B. R. G., Silverman R. H., Gale M. Jr, Diamond M. S. 2006; PKR and RNase L contribute to protection against lethal West Nile Virus infection by controlling early viral spread in the periphery and replication in neurons. J Virol 80:7009–7019 [View Article][PubMed]
     [Google Scholar]
  46. Samuel M. A., Wang H., Siddharthan V., Morrey J. D., Diamond M. S. 2007; Axonal transport mediates West Nile virus entry into the central nervous system and induces acute flaccid paralysis. Proc Natl Acad Sci U S A 104:17140–17145 [View Article][PubMed]
     [Google Scholar]
  47. Scherret J. H., Poidinger M., Mackenzie J. S., Broom A. K., Deubel V., Lipkin W. I., Briese T., Gould E. A., Hall R. A. 2001; The relationships between West Nile and Kunjin viruses. Emerg Infect Dis 7:697–705 [View Article][PubMed]
     [Google Scholar]
  48. Williams S. A., Richards J. S., Faddy H. M., Leydon J., Moran R., Nicholson S., Perry F., Paskin R., Catton M.other authors 2013; Low seroprevalence of Murray Valley encephalitis and Kunjin viruses in an opportunistic serosurvey, Victoria 2011. Aust N Z J Public Health 37:427–433 [View Article][PubMed]
     [Google Scholar]
  49. Zeller H. G., Schuffenecker I. 2004; West Nile virus: an overview of its spread in Europe and the Mediterranean basin in contrast to its spread in the Americas. Eur J Clin Microbiol Infect Dis 23:147–156 [View Article][PubMed]
     [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.063537-0
Loading
Evaluation of a mouse model for the West Nile virus group for the purpose of determining viral pathotypes
J. Gen. Virol. 95, 1221 (2014); https://doi.org/10.1099/vir.0.063537-0
/content/journal/jgv/10.1099/vir.0.063537-0
/content/journal/jgv/10.1099/vir.0.063537-0
Loading

Data & Media loading...

Most cited Most Cited RSS feed

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