1887

Abstract

Previously, we developed a model for testing the virulence and immunogenicity of vaccinia virus (VV) mutants based on the intradermal injection of BALB/c mouse ear pinnae. The model is characterized by a local infection in the inoculated skin without signs of systemic illness, mimicking dermal vaccination with VV. Here a further characterization of this model is presented, including the responses of mice to infectious virus doses as low as 10 p.f.u., a quantification of the infiltrate at the site of infection and use of different virus and mouse strains. The model was then used to compare the pathogenesis of six mutants of VV strain Western Reserve (WR) lacking genes A36R, A40R, A44L, B12R, B13R or B15R with that of appropriate control viruses. All of these genes except B12R and B15R influence the outcome of dermal infection with WR and for A40R and B13R this is the first role that has been reported after infection of mammals. A comparison of new and published results from intradermal and intranasal models is presented, showing that out of 16 gene deletion or insertion mutants of VV, half have phenotypes distinct from controls in only one of these models. Thus, the intranasal and intradermal models are complementary tools for dissecting the genetic basis of VV virulence.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/0022-1317-83-8-1977
2002-08-01
2024-04-26
Loading full text...

Full text loading...

/deliver/fulltext/jgv/83/8/0831977a.html?itemId=/content/journal/jgv/10.1099/0022-1317-83-8-1977&mimeType=html&fmt=ahah

References

  1. Alcamí A., Koszinowski U. H. 2000; Viral mechanisms of immune evasion. Trends in Microbiology 8:410–418
    [Google Scholar]
  2. Alcamí A., Smith G. L. 1992; A soluble receptor for interleukin-1 beta encoded by vaccinia virus: a novel mechanism of virus modulation of the host response to infection. Cell 71:153–167
    [Google Scholar]
  3. Alcamí A., Smith G. L. 1995; Vaccinia, cowpox, and camelpox viruses encode soluble gamma interferon receptors with novel broad species specificity. Journal of Virology 69:4633–4639
    [Google Scholar]
  4. Alcamí A., Smith G. L. 1996; A mechanism for the inhibition of fever by a virus. Proceedings of the National Academy of Sciences, USA 93:11029–11034
    [Google Scholar]
  5. Alcamí A., Smith G. L. 2002; The vaccinia virus soluble interferon-gamma receptor is a homodimer. Journal of General Virology 83:545–549
    [Google Scholar]
  6. Alcamí A., Symons J. A., Collins P. D., Williams T. J., Smith G. L. 1998; Blockade of chemokine activity by a soluble chemokine binding protein from vaccinia virus. Journal of Immunology 160:624–633
    [Google Scholar]
  7. Almazán F., Tscharke D. C., Smith G. L. 2001; The vaccinia virus superoxide dismutase-like protein (A45R) is a virion component that is nonessential for virus replication. Journal of Virology 75:7018–7029
    [Google Scholar]
  8. 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
    [Google Scholar]
  9. Banham A. H., Smith G. L. 1993; Characterization of vaccinia virus gene B12R. Journal of General Virology 74:2807–2812
    [Google Scholar]
  10. Bartlett N., Symons J. A., Tscharke D. C., Smith G. L. 2002; The vaccinia virus N1L protein is an intracellular homodimer that promotes virulence. Journal of General Virology 83:1965–1976
    [Google Scholar]
  11. Baxby D. 1981 Jenner’s Smallpox Vaccine: The Riddle of Vaccinia Virus and its Origin pp 1–214 London: Heinemann Educational;
    [Google Scholar]
  12. Belkaid Y., Jouin H., Milon G. 1996; A method to recover, enumerate and identify lymphomyeloid cells present in an inflammatory dermal site: a study in laboratory mice. Journal of Immunological Methods 199:5–25
    [Google Scholar]
  13. Blanchard T. J., Alcamí 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. Journal of General Virology 79:1159–1167
    [Google Scholar]
  14. Blasco R., Sisler J. R., Moss B. 1993; Dissociation of progeny vaccinia virus from the cell membrane is regulated by a viral envelope glycoprotein: effect of a point mutation in the lectin homology domain of the A34R gene. Journal of Virology 67:3319–3325
    [Google Scholar]
  15. Briody B. 1959; Response of mice to ectromelia and vaccinia viruses. Bacteriological Reviews 23:61–95
    [Google Scholar]
  16. Buller R. M. L., Palumbo G. J. 1991; Poxvirus pathogenesis. Microbiological Reviews 55:80–122
    [Google Scholar]
  17. Chantrey J., Meyer H., Baxby D., Begon M., Bown K. J., Hazel S. M., Jones T., Montgomery W. I., Bennett M. 1999; Cowpox: reservoir hosts and geographic range. Epidemiology and Infection 122:455–460
    [Google Scholar]
  18. Dobbelstein M., Shenk T. 1996; Protection against apoptosis by the vaccinia virus SPI-2 (B13R) gene product. Journal of Virology 70:6479–6485
    [Google Scholar]
  19. Fenner F. 1948; The clinical features and pathogenesis of mouse-pox (infectious ectromelia of mice. Journal of Pathology and Experimental Bacteriology 60:529–552
    [Google Scholar]
  20. Fenner F., Ratcliffe F. N. 1965 Myxomatosis Cambridge: Cambridge University Press;
    [Google Scholar]
  21. Fenner F., Henderson D. A., Arita I., Jezek Z., Ladnyi I. D. 1988 Smallpox and its Eradication Geneva: World Health Organization;
    [Google Scholar]
  22. Gardner J. D., Tscharke D. C., Reading P. C., Smith G. L. 2001; Vaccinia virus semaphorin A39R is a 50–55 kDa secreted glycoprotein that affects the outcome of infection in a murine intradermal model. Journal of General Virology 82:2083–2093
    [Google Scholar]
  23. Gubser C., Smith G. L. 2002; The sequence of camelpox virus shows it is most closely related to variola virus, the cause of smallpox. Journal of General Virology 83:855–872
    [Google Scholar]
  24. Hanson C. V., Riggs J. L., Lennette E. H. 1978; Photochemical inactivation of DNA and RNA viruses by psoralen derivatives. Journal of General Virology 40:345–358
    [Google Scholar]
  25. Kettle S., Blake N. W., Law K. M., Smith G. L. 1995; Vaccinia virus serpins B13R (SPI-2) and B22R (SPI-1) encode Mr 38·5 and 40K, intracellular polypeptides that do not affect virus virulence in a murine intranasal model. Virology 206:136–147
    [Google Scholar]
  26. Kettle S., Alcamí A., Khanna A., Ehret R., Jassoy C., Smith G. L. 1997; Vaccinia virus serpin B13R (SPI-2) inhibits interleukin-1β-converting enzyme and protects virus-infected cells from TNF- and Fas-mediated apoptosis, but does not prevent IL-1β-induced fever. Journal of General Virology 78:677–685
    [Google Scholar]
  27. Kotwal G. J., Hugin A. W., Moss B. 1989; Mapping and insertional mutagenesis of a vaccinia virus gene encoding a 13,800-Da secreted protein. Virology 171:579–587
    [Google Scholar]
  28. Lee M. S., Roos J. M., McGuigan L. C., Smith K. A., Cormier N., Cohen L. K., Roberts B. E., Payne L. G. 1992; Molecular attenuation of vaccinia virus: mutant generation and animal characterization. Journal of Virology 66:2617–2630
    [Google Scholar]
  29. McIntosh A. A., Smith G. L. 1996; Vaccinia virus glycoprotein A34R is required for infectivity of extracellular enveloped virus. Journal of Virology 70:272–281
    [Google Scholar]
  30. Mackett M., Smith G. L., Moss B. 1985; The construction and characterization of vaccinia virus recombinants expressing foreign genes. In DNA Cloning: a Practical Approach pp 191–211 Edited by Glover D. M. Oxford: IRL Press;
    [Google Scholar]
  31. Miller C. G., Justus D. E., Jayaraman S., Kotwal G. J. 1995; Severe and prolonged inflammatory response to localized cowpox virus infection in footpads of C5-deficient mice: investigation of the role of host complement in poxvirus pathogenesis. Cellular Immunology 162:326–332
    [Google Scholar]
  32. Moore J. B. 1992; Vaccinia virus 3 β-hydroxysteroid dehydrogenase. DPhil Thesis University of Oxford; Oxford, UK:
  33. Moore J. B., Smith G. L. 1992; Steroid hormone synthesis by a vaccinia enzyme: a new type of virus virulence factor. EMBO Journal 11:1973–1980
    [Google Scholar]
  34. Moss B., Shisler J. L. 2001; Immunology 101 at poxvirus U: immune evasion genes. Seminars in Immunology 13:59–66
    [Google Scholar]
  35. Ng A., Tscharke D. C., Reading P. C., Smith G. L. 2001; The vaccinia virus A41L protein is a soluble 30 kDa glycoprotein that affects virus virulence. Journal of General Virology 82:2095–2105
    [Google Scholar]
  36. Palumbo G. J., Pickup D. J., Fredrickson T. N., McIntyre L. J., Buller R. M. 1989; Inhibition of an inflammatory response is mediated by a 38-kDa protein of cowpox virus. Virology 172:262–273
    [Google Scholar]
  37. Panicali D., Davis S. W., Weinberg R. L., Paoletti E. 1983; Construction of live vaccines by using genetically engineered poxviruses: biological activity of recombinant vaccinia virus expressing influenza virus hemagglutinin. Proceedings of the National Academy of Sciences, USA 80:5364–5368
    [Google Scholar]
  38. Parker R. F., Bronson L. H., Green R. H. 1941; Further studies of the infectious unit of vaccinia. Journal of Experimental Medicine 74:263–281
    [Google Scholar]
  39. Parkinson J. E., Smith G. L. 1994; Vaccinia virus gene A36R encodes an Mr 43–50 K protein on the surface of extracellular enveloped virus. Virology 204:376–390
    [Google Scholar]
  40. Payne L. G. 1980; Significance of extracellular enveloped virus in the in vitro and in vivo dissemination of vaccinia virus. Journal of General Virology 50:89–100
    [Google Scholar]
  41. Pickup D. J., Ink B. S., Hu W., Ray C. A., Joklik W. K. 1986; Haemorrhage in lesions caused by cowpox virus is induced by a viral protein that is related to plasma protein inhibitors of serine proteases. Proceedings of the National Academy of Sciences, USA 83:7698–7702
    [Google Scholar]
  42. Price N., Tscharke D. C., Hollinshead M., Smith G. L. 2000; Vaccinia virus gene B7R encodes an 18-kDa protein that is resident in the endoplasmic reticulum and affects virus virulence. Virology 267:65–79
    [Google Scholar]
  43. Price N., Tscharke D. C., Smith G. L. 2002; The vaccinia virus B9R protein is a 6 kDa intracellular protein that is non-essential for virus replication. Journal of General Virology 83:873–878
    [Google Scholar]
  44. Ray C. A., Black R. A., Kronheim S. R., Greenstreet T. A., Sleath P. R., Salvesen G. S., Pickup D. J. 1992; Viral inhibition of inflammation: cowpox virus encodes an inhibitor of the interleukin-1 beta converting enzyme. Cell 69:597–604
    [Google Scholar]
  45. Röttger S., Frischknecht F., Reckmann I., Smith G. L., Way M. 1999; Interactions between vaccinia virus IEV membrane proteins and their roles in IEV assembly and actin tail formation. Journal of Virology 73:2863–2875
    [Google Scholar]
  46. Sanderson C. M., Frischknecht F., Way M., Hollinshead M., Smith G. L. 1998; Roles of vaccinia virus EEV-specific proteins in intracellular actin tail formation and low pH-induced cell-cell fusion. Journal of General Virology 79:1415–1425
    [Google Scholar]
  47. Smith G. L., Mackett M., Moss B. 1983; Infectious vaccinia virus recombinants that express hepatitis B virus surface antigen. Nature 302:490–495
    [Google Scholar]
  48. Smith G. L., Symons J. A., Khanna A., Vanderplasschen A., Alcamí A. 1997; Vaccinia virus immune evasion. Immunological Reviews 159:137–154
    [Google Scholar]
  49. Sroller V., Kutinova L., Nemeckova S., Simonova V., Vonka V. 1998; Effect of 3-beta-hydroxysteroid dehydrogenase gene deletion on virulence and immunogenicity of different vaccinia viruses and their recombinants. Archives of Virology 143:1311–1320
    [Google Scholar]
  50. Symons J. A., Tscharke D. C., Price N., Smith G. L. 2002; A study of the vaccinia virus interferon-γ receptor and its contribution to virus virulence. Journal of General Virology 83:1953–1964
    [Google Scholar]
  51. Tartaglia J., Perkus M. E., Taylor J., Norton E. K., Audonnet J. C., Cox W. I., Davis S. W., van der Hoeven J., Meignier B., Riviere M. & et al ; (1992; NYVAC: a highly attenuated strain of vaccinia virus. Virology 188:217–232
    [Google Scholar]
  52. Thompson J. P., Turner P. C., Ali A. N., Crenshaw B. C., Moyer R. W. 1993; The effects of serpin gene mutations on the distinctive pathobiology of cowpox and rabbitpox virus following intranasal inoculation of Balb/c mice. Virology 197:328–338
    [Google Scholar]
  53. Tscharke D. C., Smith G. L. 1999; A new model for vaccinia virus pathogenesis and immunity based on intradermal injection of mouse ear pinnae. Journal of General Virology 80:2751–2755
    [Google Scholar]
  54. Turner G. S. 1967; Respiratory infection of mice with vaccinia virus. Journal of General Virology 1:399–402
    [Google Scholar]
  55. van Eijl H., Hollinshead M., Smith G. L. 2000; The vaccinia virus A36R protein is a type Ib membrane protein present on intracellular but not extracellular enveloped virus particles. Virology 271:26–36
    [Google Scholar]
  56. Wilcock D., Duncan S. A., Traktman P., Zhang W.-H., Smith G. L. 1999; The vaccinia virus A40R gene product is a nonstructural, type II membrane glycoprotein that is expressed at the cell surface. Journal of General Virology 80:2137–2148
    [Google Scholar]
  57. Williamson J. D., Reith R. W., Jeffrey L. J., Arrand J. R., Mackett M. 1990; Biological characterization of recombinant vaccinia viruses in mice infected by the respiratory route. Journal of General Virology 71:2761–2767
    [Google Scholar]
  58. Wolffe E. J., Weisberg A. S., Moss B. 1998; Role for the vaccinia virus A36R outer envelope protein in the formation of virus-tipped actin-containing microvilli and cell-to-cell virus spread. Virology 244:20–26
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/0022-1317-83-8-1977
Loading
/content/journal/jgv/10.1099/0022-1317-83-8-1977
Loading

Data & Media loading...

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