1887

Abstract

Alphaviruses including Barmah Forest virus (BFV) and Ross River virus (RRV) cause arthritis, arthralgia and myalgia in humans. The rheumatic symptoms in human BFV infection are very similar to those of RRV. Although RRV disease has been studied extensively, little is known about the pathogenesis of BFV infection. We sought to establish a mouse model for BFV to facilitate our understanding of BFV infectivity, tropism and pathogenesis, and to identify key pathological and immunological mechanisms of BFV infection that may distinguish between infections with BFV and RRV. Here, to the best of our knowledge, we report the first study assessing the virulence and replication of several BFV isolates in a mouse model. We infected newborn Swiss outbred mice with BFV and established that the BFV2193 prototype was the most virulent strain. BFV2193 infection resulted in the highest mortality among all BFV variant isolates, comparable to that of RRV. In comparison with RRV, C57BL/6 mice infected with BFV showed delayed onset, moderate disease scores and early recovery of the disease. BFV replicated poorly in muscle and did not cause the severe myositis seen in RRV-infected mice. The mRNAs for the inflammatory mediators TNF-α, IL-6, CCL2 and arginase-1 were highly upregulated in RRV- but not BFV-infected muscle. To our knowledge, this is the first report of a mouse model of BFV infection, which we have used to demonstrate differences between BFV and RRV infections and to further understand disease pathogenesis. With an increasing number of BFV cases occurring annually, a better understanding of the disease mechanisms is essential for future therapeutic development.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.064733-0
2014-10-01
2019-11-13
Loading full text...

Full text loading...

/deliver/fulltext/jgv/95/10/2146.html?itemId=/content/journal/jgv/10.1099/vir.0.064733-0&mimeType=html&fmt=ahah

References

  1. Aldred J., Campbell J., Davis G., Lehmann N., Wolstenholme J.. ( 1990;). Barmah Forest virus in the Gippsland Lakes region, Victoria. . Med J Aust 153:, 434.[PubMed]
    [Google Scholar]
  2. Australian National Notifiable Diseases Surveillance System ( 2014;). Australian Department of Health National Notifiable Diseases Surveillance System. . http://www9.health.gov.au/cda/source/cda-index.cfm
  3. Boughton C. R., Hawkes R. A., Naim H. M.. ( 1988;). Illness caused by a Barmah Forest-like virus in New South Wales. . Med J Aust 148:, 146–147.[PubMed]
    [Google Scholar]
  4. Calisher C., Karabatsos N.. ( 1988;). Arbovirus Serogroups: Definition and Geographic Distribution. Boca Raton, FL:: CRC Press;.
    [Google Scholar]
  5. Deshmane S. L., Kremlev S., Amini S., Sawaya B. E.. ( 2009;). Monocyte chemoattractant protein-1 (MCP-1): an overview. . J Interferon Cytokine Res 29:, 313–326. [CrossRef][PubMed]
    [Google Scholar]
  6. Doherty R. L., Carley J. G., Kay B. H., Filippich C., Marks E. N., Frazier C. L.. ( 1979;). Isolation of virus strains from mosquitoes collected in Queensland, 1972–1976. . Aust J Exp Biol Med Sci 57:, 509–520. [CrossRef][PubMed]
    [Google Scholar]
  7. Flexman J. P., Smith D. W., Mackenzie J. S., Fraser J. R., Bass S. P., Hueston L., Lindsay M. D., Cunningham A. L.. ( 1998;). A comparison of the diseases caused by Ross River virus and Barmah Forest virus. . Med J Aust 169:, 159–163.[PubMed]
    [Google Scholar]
  8. Gardiner S. M., Compton A. M., Bennett T., Domin J., Bloom S. R.. ( 1990;). Regional hemodynamic effects of neuromedin U in conscious rats. . Am J Physiol 258:, R32–R38.[PubMed]
    [Google Scholar]
  9. Gardner J., Anraku I., Le T. T., Larcher T., Major L., Roques P., Schroder W. A., Higgs S., Suhrbier A.. ( 2010;). Chikungunya virus arthritis in adult wild-type mice. . J Virol 84:, 8021–8032. [CrossRef][PubMed]
    [Google Scholar]
  10. Gebhardt C., Németh J., Angel P., Hess J.. ( 2006;). S100A8 and S100A9 in inflammation and cancer. . Biochem Pharmacol 72:, 1622–1631. [CrossRef][PubMed]
    [Google Scholar]
  11. Gérardin P., Guernier V., Perrau J., Fianu A., Le Roux K., Grivard P., Michault A., de Lamballerie X., Flahault A., Favier F.. ( 2008;). Estimating Chikungunya prevalence in La Réunion Island outbreak by serosurveys: two methods for two critical times of the epidemic. . BMC Infect Dis 8:, 99. [CrossRef][PubMed]
    [Google Scholar]
  12. Harley D., Sleigh A., Ritchie S.. ( 2001;). Ross River virus transmission, infection, and disease: a cross-disciplinary review. . Clin Microbiol Rev 14:, 909–932. [CrossRef][PubMed]
    [Google Scholar]
  13. Herrero L. J., Nelson M., Srikiatkhachorn A., Gu R., Anantapreecha S., Fingerle-Rowson G., Bucala R., Morand E., Santos L. L., Mahalingam S.. ( 2011;). Critical role for macrophage migration inhibitory factor (MIF) in Ross River virus-induced arthritis and myositis. . Proc Natl Acad Sci U S A 108:, 12048–12053. [CrossRef][PubMed]
    [Google Scholar]
  14. Jacups S. P., Whelan P. I., Currie B. J.. ( 2008;). Ross River virus and Barmah Forest virus infections: a review of history, ecology, and predictive models, with implications for tropical northern Australia. . Vector Borne Zoonotic Dis 8:, 283–298. [CrossRef][PubMed]
    [Google Scholar]
  15. Jeffery J. A., Kay B. H., Ryan P. A.. ( 2006;). Role of Verrallina funerea (Diptera: Culicidae) in transmission of Barmah Forest virus and Ross River virus in coastal areas of eastern Australia. . J Med Entomol 43:, 1239–1247. [CrossRef][PubMed]
    [Google Scholar]
  16. Lee E., Stocks C., Lobigs P., Hislop A., Straub J., Marshall I., Weir R., Dalgarno L.. ( 1997;). Nucleotide sequence of the Barmah Forest virus genome. . Virology 227:, 509–514. [CrossRef][PubMed]
    [Google Scholar]
  17. Lidbury B. A., Mahalingam S.. ( 2000;). Specific ablation of antiviral gene expression in macrophages by antibody-dependent enhancement of Ross River virus infection. . J Virol 74:, 8376–8381. [CrossRef][PubMed]
    [Google Scholar]
  18. Lidbury B. A., Simeonovic C., Maxwell G. E., Marshall I. D., Hapel A. J.. ( 2000;). Macrophage-induced muscle pathology results in morbidity and mortality for Ross River virus-infected mice. . J Infect Dis 181:, 27–34. [CrossRef][PubMed]
    [Google Scholar]
  19. Lidbury B. A., Rulli N. E., Suhrbier A., Smith P. N., McColl S. R., Cunningham A. L., Tarkowski A., van Rooijen N., Fraser R. J., Mahalingam S.. ( 2008;). Macrophage-derived proinflammatory factors contribute to the development of arthritis and myositis after infection with an arthrogenic alphavirus. . J Infect Dis 197:, 1585–1593. [CrossRef][PubMed]
    [Google Scholar]
  20. Lidbury B. A., Rulli N. E., Musso C. M., Cossetto S. B., Zaid A., Suhrbier A., Rothenfluh H. S., Rolph M. S., Mahalingam S.. ( 2011;). Identification and characterization of a ross river virus variant that grows persistently in macrophages, shows altered disease kinetics in a mouse model, and exhibits resistance to type I interferon. . J Virol 85:, 5651–5663. [CrossRef][PubMed]
    [Google Scholar]
  21. Marshall I. D., Thibos E., Clarke K.. ( 1982;). Species composition of mosquitoes collected in the Murray Valley of South-eastern Australia during an epidemic of arboviral encephalitis. . Aust J Exp Biol Med Sci 60:, 447–456. [CrossRef][PubMed]
    [Google Scholar]
  22. McGill P. E.. ( 1995;). Viral infections: α-viral arthropathy. . Baillieres Clin Rheumatol 9:, 145–150. [CrossRef][PubMed]
    [Google Scholar]
  23. Morrison T. E., Whitmore A. C., Shabman R. S., Lidbury B. A., Mahalingam S., Heise M. T.. ( 2006;). Characterization of Ross River virus tropism and virus-induced inflammation in a mouse model of viral arthritis and myositis. . J Virol 80:, 737–749. [CrossRef][PubMed]
    [Google Scholar]
  24. Morrison T. E., Fraser R. J., Smith P. N., Mahalingam S., Heise M. T.. ( 2007;). Complement contributes to inflammatory tissue destruction in a mouse model of Ross River virus-induced disease. . J Virol 81:, 5132–5143. [CrossRef][PubMed]
    [Google Scholar]
  25. Morrison T. E., Simmons J. D., Heise M. T.. ( 2008;). Complement receptor 3 promotes severe ross river virus-induced disease. . J Virol 82:, 11263–11272. [CrossRef][PubMed]
    [Google Scholar]
  26. Poidinger M., Roy S., Hall R. A., Turley P. J., Scherret J. H., Lindsay M. D., Broom A. K., Mackenzie J. S.. ( 1997;). Genetic stability among temporally and geographically diverse isolates of Barmah Forest virus. . Am J Trop Med Hyg 57:, 230–234.[PubMed]
    [Google Scholar]
  27. Reinarz A. B. G., Broome M. G., Sagik B. P.. ( 1971;). Age-dependent resistance of mice to Sindbis virus infection: viral replication as a function of host age. . Infect Immun 3:, 268–273.[PubMed]
    [Google Scholar]
  28. Rohatgi A., Corbo J. C., Monte K., Higgs S., Vanlandingham D. L., Kardon G., Lenschow D. J., Perlman S.. ( 2014;). Infection of myofibers contributes to increased pathogenicity during infection with an epidemic strain of chikungunya virus. . J Virol 88:, 2414–2425. [CrossRef][PubMed]
    [Google Scholar]
  29. Rulli N. E., Guglielmotti A., Mangano G., Rolph M. S., Apicella C., Zaid A., Suhrbier A., Mahalingam S.. ( 2009;). Amelioration of alphavirus-induced arthritis and myositis in a mouse model by treatment with bindarit, an inhibitor of monocyte chemotactic proteins. . Arthritis Rheum 60:, 2513–2523. [CrossRef][PubMed]
    [Google Scholar]
  30. Ryman K. D., Gardner C. L., Meier K. C., Biron C. A., Johnston R. E., Klimstra W. B.. ( 2007;). Early restriction of alphavirus replication and dissemination contributes to age-dependent attenuation of systemic hyperinflammatory disease. . J Gen Virol 88:, 518–529. [CrossRef][PubMed]
    [Google Scholar]
  31. Standfast H. A., Dyce A. L., St George T. D., Muller M. J., Doherty R. L., Carley J. G., Filippich C.. ( 1984;). Isolation of arboviruses from insects collected at Beatrice Hill, Northern Territory of Australia, 1974-1976. . Aust J Biol Sci 37:, 351–366.[PubMed]
    [Google Scholar]
  32. Suhrbier A., Mahalingam S.. ( 2009;). The immunobiology of viral arthritides. . Pharmacol Ther 124:, 301–308. [CrossRef][PubMed]
    [Google Scholar]
  33. Vale T. G., Carter I. W., McPhie K. A., James G. S., Cloonan M. J.. ( 1986;). Human arbovirus infections along the south coast of New South Wales. . Aust J Exp Biol Med Sci 64:, 307–309. [CrossRef][PubMed]
    [Google Scholar]
  34. Zawatzky R., Gresser I., DeMaeyer E., Kirchner H.. ( 1982;). The role of interferon in the resistance of C57BL/6 mice to various doses of herpes simplex virus type 1. . J Infect Dis 146:, 405–410. [CrossRef][PubMed]
    [Google Scholar]
  35. Ziegler S. A., Lu L., da Rosa A. P., Xiao S. Y., Tesh R. B.. ( 2008;). An animal model for studying the pathogenesis of chikungunya virus infection. . Am J Trop Med Hyg 79:, 133–139.[PubMed]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.064733-0
Loading
/content/journal/jgv/10.1099/vir.0.064733-0
Loading

Data & Media loading...

Supplements

Supplementary Data 

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