1887

Journal of General Virology header logo

Volume 87, Issue 7

Pathogenesis of Dugbe virus infection in wild-type and interferon-deficient mice Free

Abstract

In 129 mice, infection with the nairovirus (DUGV) was lethal following intracerebral but not intraperitoneal inoculation. Following both routes of inoculation, immunostaining of tissue sections demonstrated virus-positive cells in the brain, indicating that DUGV is neuroinvasive in mice. Many brain areas were affected and neurones were the main cell type infected. Infected cells showed punctate accumulations of viral nucleoprotein in the cytoplasm, indicative of virus replication sites. Immunostaining for activated caspase 3 demonstrated no evidence of apoptosis. The type I interferon (IFN) system plays a significant role in defence against DUGV, as 129 IFN-/ R mice died rapidly following both intraperitoneal and intracerebral inoculations. Studies were undertaken to determine whether the IFN-inducible proteins, protein kinase R (PKR) and MxA, were important for protection; neither PKR nor constitutively expressed human MxA played significant roles.

  • Received:
  • Accepted:
  • Published Online:
SGM
Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.81767-0
2006-07-01
2024-04-27
Loading full text...

Full text loading...

/deliver/fulltext/jgv/87/7/2005.html?itemId=/content/journal/jgv/10.1099/vir.0.81767-0&mimeType=html&fmt=ahah

References

  1. Andersson I., Bladh L., Mousavi-Jazi M., Magnusson K.-E., Lundkvist Å., 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. Andersson I., Lundkvist Å., Haller O., Mirazimi A. 2006; Type I interferon inhibits Crimean-Congo hemorrhagic fever virus in human target cells. J Med Virol 78:216–222 [CrossRef]
     [Google Scholar]
  3. Blakqori G., Weber F. 2005; Efficient cDNA-based rescue of La Crosse bunyaviruses expressing or lacking the nonstructural protein NSs. J Virol 79:10420–10428 [CrossRef]
     [Google Scholar]
  4. Bridgen A., Dalrymple D. A., Elliott R. M. 2002; Dugbe nairovirus S segment: correction of the sequence and comparison of five isolates. Virology 294:364–371 [CrossRef]
     [Google Scholar]
  5. Bridgen A., Dalrymple D. A., Weber F., Elliott R. M. 2004; Inhibition of Dugbe nairovirus replication by human MxA protein. Virus Res 99:47–50 [CrossRef]
     [Google Scholar]
  6. Buckley A., Higgs S., Gould E. A. 1990; Dugbe virus susceptibility to neutralization by monoclonal antibodies as a marker of virulence in mice. Arch Virol, Supplementum 1:197–205
     [Google Scholar]
  7. Burt F. J., Swanepoel R. 2005; Molecular epidemiology of African and Asian Crimean-Congo haemorrhagic fever isolates. Epidemiol Infect 133:659–666 [CrossRef]
     [Google Scholar]
  8. Burt F. J., Spencer D. C., Leman P. A., Patterson B., Swanepoel R. 1996; Investigation of tick-borne viruses as pathogens of humans in South Africa and evidence of Dugbe virus infection in a patient with prolonged thrombocytopenia. Epidemiol Infect 116:353–361 [CrossRef]
     [Google Scholar]
  9. Coates D. M., Sweet C. 1990; Studies on the pathogenicity of a nairovirus, Dugbe virus, in normal and immunosuppressed mice. J Gen Virol 71:325–332 [CrossRef]
     [Google Scholar]
  10. Colón-Ramos D. A., Irusta P. M., Gan E. C. & 9 other authors 2003; Inhibition of translation and induction of apoptosis by bunyaviral nonstructural proteins bearing sequence similarity to reaper. Mol Biol Cell 14:4162–4172 [CrossRef]
     [Google Scholar]
  11. David-West T. S., Porterfield J. S. 1974; Dugbe virus: a tick-borne arbovirus from Nigeria. J Gen Virol 23:297–307 [CrossRef]
     [Google Scholar]
  12. Elliott R. M., Bouloy M., Calisher C. H., Goldbach R., Moyer J. T., Nichol S. T., Pettersson R., Plyusnin A., Schmaljohn C. S. 2000; Bunyaviridae . In Virus Taxonomy. Seventh Report of the International Committee on Taxonomy of Viruses pp  599–621 Edited by van Regenmortel M. H. V., Fauquet C. M., Bishop D. H. L., Carstens E. B., Estes M. K., Lemon S. M., Maniloff J., Mayo M. A., McGeoch D. J., Pringle C. R., Wickner R. B. San Diego: Academic Press;
     [Google Scholar]
  13. Frese M., Kochs G., Feldmann H., Hertkorn C., Haller O. 1996; Inhibition of bunyaviruses, phleboviruses, and hantaviruses by human MxA protein. J Virol 70:915–923
     [Google Scholar]
  14. 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]
  15. Haller O., Frese M., Kochs G. 1998; Mx proteins: mediators of innate resistance to RNA viruses. Rev Sci Tech 17:220–230
     [Google Scholar]
  16. Hardestam J., Klingström J., Mattsson K., Lundkvist Å. 2005; HFRS causing hantaviruses do not induce apoptosis in confluent Vero E6 and A-549 cells. J Med Virol 76:234–240 [CrossRef]
     [Google Scholar]
  17. Hefti H. P., Frese M., Landis H., Di Paolo C., Aguzzi A., Haller O., Pavlovic J. 1999; Human MxA protein protects mice lacking a functional alpha/beta interferon system against La Crosse virus and other lethal viral infections. J Virol 73:6984–6991
     [Google Scholar]
  18. Hoogstraal H. 1979; The epidemiology of tick-borne Crimean-Congo haemorrhagic fever in Asia, Europe and Africa. J Med Entomol 15:307–417 [CrossRef]
     [Google Scholar]
  19. Khaiboullina S. F., Rizvanov A. A., Otteson E., Miyazato A., Maciejewski J., St Jeor S. 2004; Regulation of cellular gene expression in endothelial cells by Sin Nombre and Prospect Hill viruses. Viral Immunol 17:234–251 [CrossRef]
     [Google Scholar]
  20. Kochs G., Janzen C., Hohenberg H., Haller O. 2002; Antivirally active MxA protein sequesters La Crosse virus nucleocapsid protein into perinuclear complexes. Proc Natl Acad Sci U S A 99:3153–3158 [CrossRef]
     [Google Scholar]
  21. Kohl A., Clayton R. F., Weber F., Bridgen A., Randall R. E., Elliott R. M. 2003; Bunyamwera virus nonstructural protein NSs counteracts interferon regulatory factor 3-mediated induction of early cell death. J Virol 77:7999–8008 [CrossRef]
     [Google Scholar]
  22. Li X.-D., Kukkonen S., Vapalahti O., Plyusnin A., Lankinen H., Vaheri A. 2004; Tula hantavirus infection of Vero E6 cells induces apoptosis involving caspase 8 activation. J Gen Virol 85:3261–3268 [CrossRef]
     [Google Scholar]
  23. Marriott A. C., Nuttall P. A. 1996; Molecular biology of nairoviruses. In The Bunyaviridae pp  91–104 Edited by Elliott R. M. New York: Plenum;
     [Google Scholar]
  24. Müller U., Steinhoff U., Reis L. F. L., 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]
  25. Nam J.-H., Hwang K.-A., Yu C.-H. & 7 other authors 2003; Expression of interferon inducible genes following Hantaan virus infection as a mechanism of resistance in A549 cells. Virus Genes 26:31–38 [CrossRef]
     [Google Scholar]
  26. Papa A., Ma B., Kouidou S., Tang Q., Hang C., Antoniadis A. 2002; Genetic characterization of the M RNA segment of Crimean Congo hemorrhagic fever virus strains, China. Emerg Infect Dis 8:50–53 [CrossRef]
     [Google Scholar]
  27. Pavlovic J., Arzet H. A., Hefti H. P., Frese M., Rost D., Ernst B., Kolb E., Staeheli P., Haller O. 1995; Enhanced virus resistance of transgenic mice expressing the human MxA protein. J Virol 69:4506–4510
     [Google Scholar]
  28. Pekosz A., Phillips J., Pleasure D., Merry D., Gonzalez-Scarano F. 1996; Induction of apoptosis by La Crosse virus infection and role of neuronal differentiation and human bcl-2 expression in its prevention. J Virol 70:5329–5335
     [Google Scholar]
  29. Sanchez A. J., Vincent M. J., Nichol S. T. 2002; Characterization of the glycoproteins of Crimean-Congo hemorrhagic fever virus. J Virol 76:7263–7275 [CrossRef]
     [Google Scholar]
  30. Sanchez A. J., Vincent M. J., Erickson B. R., Nichol S. T. 2006; Crimean-Congo hemorrhagic fever virus glycoprotein precursor is cleaved by furin-like and SKI-1 proteases to generate a novel 38-kilodalton glycoprotein. J Virol 80:514–525 [CrossRef]
     [Google Scholar]
  31. Silverman R. H. 1994; Fascination with 2-5A-dependent RNase: a unique enzyme that functions in interferon action. J Interferon Res 14:101–104 [CrossRef]
     [Google Scholar]
  32. Smirnova S. E., Shestopalova N. M., Reingold V. N., Zubri G. L., Chumakov M. P. 1977; Experimental Hazara virus infection in mice. Acta Virol 21:128–132
     [Google Scholar]
  33. Stark G. R., Kerr I. M., Williams B. R., Silverman R. H., Schreiber R. D. 1998; How cells respond to interferons. Annu Rev Biochem 67:227–264 [CrossRef]
     [Google Scholar]
  34. Streitenfeld H., Boyd A., Fazakerley J. K., Bridgen A., Elliott R. M., Weber F. 2003; Activation of PKR by Bunyamwera virus is independent of the viral interferon antagonist NSs. J Virol 77:5507–5511 [CrossRef]
     [Google Scholar]
  35. 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]
  36. 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]
  37. Watret G. E., Pringle C. R., Elliott R. M. 1985; Synthesis of bunyavirus-specific proteins in a continuous cell line (XTC-2) derived from Xenopus laevis . J Gen Virol 66:473–482 [CrossRef]
     [Google Scholar]
  38. Whitehouse C. A. 2004; Crimean-Congo hemorrhagic fever. Antiviral Res 64:145–160 [CrossRef]
     [Google Scholar]
  39. Williams B. R. 1999; PKR; a sentinel kinase for cellular stress. Oncogene 18:6112–6120 [CrossRef]
     [Google Scholar]
  40. Yang Y.-L., Reis L. F. L., Pavlovic J., Aguzzi A., Schäfer R., Kumar A., Williams B. R. G., Aguet M., Weissmann C. 1995; Deficient signaling in mice devoid of double-stranded RNA-dependent protein kinase. EMBO J 24:6095–6106
     [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.81767-0
Loading
Pathogenesis of Dugbe virus infection in wild-type and interferon-deficient mice
J. Gen. Virol. 87, 2005 (2006); https://doi.org/10.1099/vir.0.81767-0
/content/journal/jgv/10.1099/vir.0.81767-0
/content/journal/jgv/10.1099/vir.0.81767-0
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