1887

Abstract

Vaccinia virus (VACV) encodes multiple proteins to evade host innate immunity, including B14, a virulence factor that binds to the inhibitor of B kinase (IKK) and blocks nuclear factor B (NF-B) activation. B14 shares 95 % amino acid identity with the 183 protein encoded by modified virus Ankara (MVA), an attenuated VACV strain being developed as a vaccine vector. To evaluate whether the immunogenicity of MVA might be increased by manipulation of MVA immunomodulatory proteins, the MVA counterpart of B14, protein 183, was characterized. Unlike B14, protein 183 was unstable in eukaryotic cells unless proteasome-mediated protein degradation was inhibited. Furthermore, 183 did not inhibit NF-B activation in response to cytokine stimulation, and did not restore the virulence of VACV strain Western Reserve lacking gene . The instability and non-functionality of 183 are probably explained by a deletion of 6 aa within -helix 6 of the B14 crystal structure.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.022343-0
2010-09-01
2024-03-29
Loading full text...

Full text loading...

/deliver/fulltext/jgv/91/9/2216.html?itemId=/content/journal/jgv/10.1099/vir.0.022343-0&mimeType=html&fmt=ahah

References

  1. Antoine, G., Scheiflinger, F., Dorner, F. & Falkner, F. G.(1998). The complete genomic sequence of the modified vaccinia Ankara strain: comparison with other orthopoxviruses. Virology 244, 365–396.[CrossRef] [Google Scholar]
  2. Blanchard, T. J., Alcami, A., Andrea, P. & Smith, G. L.(1998). Modified vaccinia virus Ankara undergoes limited replication in human cells and lacks several immunomodulatory proteins: implications for use as a human vaccine. J Gen Virol 79, 1159–1167. [Google Scholar]
  3. Chen, R. A., Jacobs, N. & Smith, G. L.(2006). Vaccinia virus strain Western Reserve protein B14 is an intracellular virulence factor. J Gen Virol 87, 1451–1458.[CrossRef] [Google Scholar]
  4. Chen, R. A., Ryzhakov, G., Cooray, S., Randow, F. & Smith, G. L.(2008). Inhibition of IκB kinase by vaccinia virus virulence factor B14. PLoS Pathog 4, e22[CrossRef] [Google Scholar]
  5. Clark, R. H., Kenyon, J. C., Bartlett, N. W., Tscharke, D. C. & Smith, G. L.(2006). Deletion of gene A41L enhances vaccinia virus immunogenicity and vaccine efficacy. J Gen Virol 87, 29–38.[CrossRef] [Google Scholar]
  6. Falkner, F. G. & Moss, B.(1990). Transient dominant selection of recombinant vaccinia viruses. J Virol 64, 3108–3111. [Google Scholar]
  7. Fenner, F., Anderson, D. A., Arita, I., Jezek, Z. & Ladnyi, I. D.(1988).Smallpox and its Eradication. Geneva: World Health Organization.
  8. Graham, S. C., Bahar, M. W., Cooray, S., Chen, R. A., Whalen, D. M., Abrescia, N. G., Alderton, D., Owens, R. J., Stuart, D. I. & other authors(2008). Vaccinia virus proteins A52 and B14 share a Bcl-2-like fold but have evolved to inhibit NF-κB rather than apoptosis. PLoS Pathog 4, e1000128[CrossRef] [Google Scholar]
  9. Hashizume, S., Yoshizawa, H., Morita, M. & Suzuki, K.(1985). Properties of attenuated mutant of vaccinia virus, LC16m8, derived from Lister strain. In Vaccinia Viruses as Vectors for Vaccine Antigens, pp. 87–99. Edited by G. V. Quinnan. New York: Elsevier Science.
  10. Hughes, S. J., Johnston, L. H., de Carlos, A. & Smith, G. L.(1991). Vaccinia virus encodes an active thymidylate kinase that complements a cdc8 mutant of Saccharomyces cerevisiae. J Biol Chem 266, 20103–20109. [Google Scholar]
  11. Lane, J. M., Ruben, F. L., Neff, J. M. & Millar, J. D.(1969). Complications of smallpox vaccination, 1968. National surveillance in the United States. N Engl J Med 281, 1201–1208.[CrossRef] [Google Scholar]
  12. Mahnel, H. & Mayr, A.(1994). Experiences with immunization against orthopox viruses of humans and animals using vaccine strain MVA. Berl Munch Tierarztl Wochenschr 107, 253–256 (in German). [Google Scholar]
  13. Mayr, A. & Munz, E.(1964). Changes in the vaccinia virus through continuing passages in chick embryo fibroblast cultures. Zentralbl Bakteriol Orig 195, 24–35 (in German). [Google Scholar]
  14. Mayr, A., Stickl, H., Muller, H. K., Danner, K. & Singer, H.(1978). The smallpox vaccination strain MVA: marker, genetic structure, experience gained with the parenteral vaccination and behavior in organisms with a debilitated defence mechanism. Zentralbl Bakteriol [B] 167, 375–390 (in German). [Google Scholar]
  15. Meisinger-Henschel, C., Schmidt, M., Lukassen, S., Linke, B., Krause, L., Konietzny, S., Goesmann, A., Howley, P., Chaplin, P. & other authors(2007). Genomic sequence of chorioallantois vaccinia virus Ankara, the ancestor of modified vaccinia virus Ankara. J Gen Virol 88, 3249–3259.[CrossRef] [Google Scholar]
  16. Meyer, H., Sutter, G. & Mayr, A.(1991). Mapping of deletions in the genome of the highly attenuated vaccinia virus MVA and their influence on virulence. J Gen Virol 72, 1031–1038.[CrossRef] [Google Scholar]
  17. Moss, B.(2007).Poxviridae: the viruses and their replicaton. In Fields Virology, 5th edn, pp. 2905–2946. Edited by D. M. Knipe & P. M. Howley. Philadelphia, PA: Lippincott Williams & Wilkins.
  18. Oie, K. L. & Pickup, D. J.(2001). Cowpox virus and other members of the orthopoxvirus genus interfere with the regulation of NF-κB activation. Virology 288, 175–187.[CrossRef] [Google Scholar]
  19. Parkinson, J. E. & Smith, G. L.(1994). Vaccinia virus gene A36R encodes a Mr 43–50 K protein on the surface of extracellular enveloped virus. Virology 204, 376–390.[CrossRef] [Google Scholar]
  20. Satheshkumar, P. S., Anton, L. C., Sanz, P. & Moss, B.(2009). Inhibition of the ubiquitin–proteasome system prevents vaccinia virus DNA replication and expression of intermediate and late genes. J Virol 83, 2469–2479.[CrossRef] [Google Scholar]
  21. Smith, G. L., Mackett, M. & Moss, B.(1983). Infectious vaccinia virus recombinants that express hepatitis B virus surface antigen. Nature 302, 490–495.[CrossRef] [Google Scholar]
  22. Staib, C., Kisling, S., Erfle, V. & Sutter, G.(2005). Inactivation of the viral interleukin 1β receptor improves CD8+ T-cell memory responses elicited upon immunization with modified vaccinia virus Ankara. J Gen Virol 86, 1997–2006.[CrossRef] [Google Scholar]
  23. Stickl, H., Hochstein-Mintzel, V., Mayr, A., Huber, H. C., Schafer, H. & Holzner, A.(1974). MVA vaccination against smallpox: clinical tests with an attenuated live vaccinia virus strain (MVA). Dtsch Med Wochenschr 99, 2386–2392 (in German).[CrossRef] [Google Scholar]
  24. Sutter, G. & Moss, B.(1992). Nonreplicating vaccinia vector efficiently expresses recombinant genes. Proc Natl Acad Sci U S A 89, 10847–10851.[CrossRef] [Google Scholar]
  25. Tscharke, D. C. & Smith, G. L.(1999). A model for vaccinia virus pathogenesis and immunity based on intradermal injection of mouse ear pinnae. J Gen Virol 80, 2751–2755. [Google Scholar]
  26. Tscharke, D. C., Reading, P. C. & Smith, G. L.(2002). Dermal infection with vaccinia virus reveals roles for virus proteins not seen using other inoculation routes. J Gen Virol 83, 1977–1986. [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.022343-0
Loading
/content/journal/jgv/10.1099/vir.0.022343-0
Loading

Data & Media loading...

Supplements

vol. , part 9, pp. 2216–2220

PCR analysis of the locus [ PDF] (75 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