1887

Abstract

Crimean–Congo hemorrhagic fever virus (CCHFV) poses a great threat to public health due to its high mortality, transmission and geographical distribution. To date, there is no vaccine or specific treatment available and the knowledge regarding its pathogenesis is highly limited. Using a small-animal model system, this study showed that adult mice missing the type I interferon (IFN) receptor (IFNAR) were susceptible to CCHFV and developed an acute disease with fatal outcome. In contrast, infection of wild-type mice (129 Sv/Ew) was asymptomatic. Viral RNA was found in all analysed organs of the infected mice, but the amount of CCHFV RNA was significantly higher in the IFNAR mice than in the wild-type mice. Furthermore, the liver of IFNAR mice was enlarged significantly, showing that IFN is important for limiting virus spread and protecting against liver damage in mice.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.019034-0
2010-06-01
2024-03-29
Loading full text...

Full text loading...

/deliver/fulltext/jgv/91/6/1473.html?itemId=/content/journal/jgv/10.1099/vir.0.019034-0&mimeType=html&fmt=ahah

References

  1. Andersson, I., Bladh, L., Mousavi-Jazi, M., Magnusson, K. E., Lundkvist, A., Haller, O. & Mirazimi, A.(2004). Human MxA protein inhibits the replication of Crimean–Congo hemorrhagic fever virus. J Virol 78, 4323–4329.[CrossRef] [Google Scholar]
  2. Bakir, M., Ugurlu, M., Dokuzoguz, B., Bodur, H., Tasyaran, M. A. & Vahaboglu, H.(2005). Crimean–Congo haemorrhagic fever outbreak in Middle Anatolia: a multicentre study of clinical features and outcome measures. J Med Microbiol 54, 385–389.[CrossRef] [Google Scholar]
  3. Baskerville, A., Satti, A., Murphy, F. A. & Simpson, D. I.(1981). Congo–Crimean haemorrhagic fever in Dubai: histopathological studies. J Clin Pathol 34, 871–874.[CrossRef] [Google Scholar]
  4. Bouloy, M., Janzen, C., Vialat, P., Khun, H., Pavlovic, J., Huerre, M. & Haller, O.(2001). Genetic evidence for an interferon-antagonistic function of Rift Valley fever virus non-structural protein NSs. J Virol 75, 1371–1377.[CrossRef] [Google Scholar]
  5. Boyd, A., Fazakerley, J. K. & Bridgen, A.(2006). Pathogenesis of Dugbe virus infection in wild-type and interferon-deficient mice. J Gen Virol 87, 2005–2009.[CrossRef] [Google Scholar]
  6. Burt, F. J., Swanepoel, R. & Braack, L. E.(1993). Enzyme-linked immunosorbent assays for the detection of antibody to Crimean–Congo haemorrhagic fever virus in the sera of livestock and wild vertebrates. Epidemiol Infect 111, 547–557.[CrossRef] [Google Scholar]
  7. Ergonul, O.(2006). Crimean–Congo haemorrhagic fever. Lancet Infect Dis 6, 203–214.[CrossRef] [Google Scholar]
  8. Gonzalez, J. P., Wilson, M. L., Cornet, J. P. & Camicas, J. L.(1995). Host-passage-induced phenotypic changes in Crimean–Congo haemorrhagic fever virus. Res Virol 146, 131–140.[CrossRef] [Google Scholar]
  9. Gonzalez, J. P., Camicas, J. L., Cornet, J. P. & Wilson, M. L.(1998). Biological and clinical responses of west African sheep to Crimean–Congo haemorrhagic fever virus experimental infection. Res Virol 149, 445–455.[CrossRef] [Google Scholar]
  10. Hoogstraal, H.(1979). The epidemiology of tick borne Crimean–Congo hemorrhagic fever in Asia, Europe and Africa. J Med Entomol 15, 307–417.[CrossRef] [Google Scholar]
  11. Huang, S., Hendriks, W., Althage, A., Hemmi, S., Bluethmann, H., Kamijo, R., Vilcek, J., Zinkernagel, R. M. & Aguet, M.(1993). Immune response in mice that lack the interferon-gamma receptor. Science 259, 1742–1745.[CrossRef] [Google Scholar]
  12. Hwang, S. Y., Hertzog, P. J., Holland, K. A., Sumarsono, S. H., Tymms, M. J., Hamilton, J. A., Whitty, G., Bertoncello, I. & Kola, I.(1995). A null mutation in the gene encoding a type I interferon receptor component eliminates antiproliferative and antiviral responses to interferons alpha and beta and alters macrophage responses. Proc Natl Acad Sci U S A 92, 11284–11288.[CrossRef] [Google Scholar]
  13. Khan, A. S., Maupin, G. O., Rollin, P. E., Noor, A. M., Shurie, H. H., Shalabi, A. G., Wasef, S., Haddad, Y. M., Sadek, R. & other authors(1997). An outbreak of Crimean–Congo hemorrhagic fever in the United Arab Emirates, 1994–1995. Am J Trop Med Hyg 57, 519–525. [Google Scholar]
  14. Mariner, J. C., Morrill, J. & Ksiazek, T. G.(1995). Antibodies to hemorrhagic fever viruses in domestic livestock in Niger: Rift Valley fever and Crimean–Congo hemorrhagic fever. Am J Trop Med Hyg 53, 217–221. [Google Scholar]
  15. Muller, U., Steinhoff, U., Reis, L. F., Hemmi, S., Pavlovic, J., Zinkernagel, R. M. & Aguet, M.(1994). Functional role of type I and type II interferons in antiviral defense. Science 264, 1918–1921.[CrossRef] [Google Scholar]
  16. Nabeth, P., Cheikh, D. O., Lo, B., Faye, O., Vall, I. O., Niang, M., Wague, B., Diop, D., Diallo, M. & other authors(2004). Crimean–Congo hemorrhagic fever, Mauritania. Emerg Infect Dis 10, 2143–2149.[CrossRef] [Google Scholar]
  17. Schwarz, T. F., Nsanze, H. & Ameen, A. M.(1997). Clinical features of Crimean–Congo haemorrhagic fever in the United Arab Emirates. Infection 25, 364–367.[CrossRef] [Google Scholar]
  18. Shepherd, A. J., Leman, P. A. & Swanepoel, R.(1989). Viremia and antibody response of small African and laboratory animals to Crimean–Congo hemorrhagic fever virus infection. Am J Trop Med Hyg 40, 541–547. [Google Scholar]
  19. Smirnova, S. E., Zubri, G. L., Savinov, A. P. & Chumakov, M. P.(1973). Pathogenesis of experimental Crimean haemorrhagic fever infection in newborn white mice. Acta Virol 17, 409–415. [Google Scholar]
  20. Spik, K., Shurtleff, A., McElroy, A. K., Guttieri, M. C., Hooper, J. W. & Schmaljohn, C.(2006). Immunogenicity of combination DNA vaccines for Rift Valley fever virus, tick-borne encephalitis virus, Hantaan virus, and Crimean Congo hemorrhagic fever virus. Vaccine 24, 4657–4666.[CrossRef] [Google Scholar]
  21. Swanepoel, R., Shepherd, A. J., Leman, P. A., Shepherd, S. P., McGillivray, G. M., Erasmus, M. J., Searle, L. A. & Gill, D. E.(1987). Epidemiologic and clinical features of Crimean–Congo hemorrhagic fever in southern Africa. Am J Trop Med Hyg 36, 120–132. [Google Scholar]
  22. Swanepoel, R., Gill, D. E., Shepherd, A. J., Leman, P. A., Mynhardt, J. H. & Harvey, S.(1989). The clinical pathology of Crimean–Congo hemorrhagic fever. Rev Infect Dis 11, S794–S800.[CrossRef] [Google Scholar]
  23. Swanepoel, R., Leman, P. A., Burt, F. J., Jardine, J., Verwoerd, D. J., Capua, I., Brückner, G. K. & Burger, W. P.(1998). Experimental infection of ostriches with Crimean–Congo haemorrhagic fever virus. Epidemiol Infect 121, 427–432.[CrossRef] [Google Scholar]
  24. Tignor, G. H. & Hanham, C. A.(1993). Ribavirin efficacy in an in vivo model of Crimean–Congo hemorrhagic fever virus (CCHF) infection. Antiviral Res 22, 309–325.[CrossRef] [Google Scholar]
  25. Weber, F. & Mirazimi, A.(2008). Interferon and cytokine responses to Crimean Congo hemorrhagic fever virus; an emerging and neglected viral zoonosis. Cytokine Growth Factor Rev 19, 395–404.[CrossRef] [Google Scholar]
  26. Wölfel, R., Paweska, J. T., Petersen, N., Grobbelaar, A. A., Leman, P. A., Hewson, R., Georges-Courbot, M. C., Papa, A., Günther, S. & Drosten, C.(2007). Virus detection and monitoring of viral load in Crimean–Congo hemorrhagic fever virus patients. Emerg Infect Dis 13, 1097–1100.[CrossRef] [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.019034-0
Loading
/content/journal/jgv/10.1099/vir.0.019034-0
Loading

Data & Media loading...

Supplements

vol. , part 6, pp. 1473–1477

Enlarged liver with haemorrhage from a CCHFV (10  f.f.u.)-infected IFNAR mouse, 68 h post-infection [ PDF] (63 KB)



PDF
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