1887

Abstract

Vaccinia virus (VV) protein A39R has amino acid similarity to the extracellular domain of a glycosylphosphatidylinositol-linked cell surface semaphorin (SEMA7A/CDw108) that has an immunological expression profile and binding properties, thereby implicating A39R as an immunomodulator. Previously, a closely related A39R protein expressed by ectromelia virus was shown to induce cytokine production and up-regulate ICAM-1 expression in mouse monocytes . In this study, we show that the gene of VV strain Copenhagen (COP) encodes a 50–55 kDa secreted glycoprotein and is expressed late during infection. The A39R protein was secreted by eight of 15 strains of VV, but not by strain Western Reserve (WR). To analyse the VV A39R function, several recombinant viruses were made, including an deletion mutant of VV COP and a WR mutant containing the sequence from COP. Loss of the gene from COP did not affect virus growth , or VV virulence in a mouse intranasal model, and had only a slight effect on lesion size in an intradermal model. In contrast, expression of COP by VV WR was associated with an increase in the severity and persistence of skin lesions after intradermal infection of mice. Finally, a histological examination of mouse skin infected with recombinant viruses suggested that A39R has direct or indirect pro-inflammatory properties.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/0022-1317-82-9-2083
2001-09-01
2024-12-14
Loading full text...

Full text loading...

/deliver/fulltext/jgv/82/9/0822083a.html?itemId=/content/journal/jgv/10.1099/0022-1317-82-9-2083&mimeType=html&fmt=ahah

References

  1. Afonso C. L., Tulman E. R., Lu Z., Zsak L., Kutish G. F., Rock D. L. 2000; The genome of fowlpox virus. Journal of Virology 74:3815–3831
    [Google Scholar]
  2. Aguado B., Selmes I. P., Smith G. L. 1992; Nucleotide sequence of 21·8 kbp of variola major virus strain Harvey and comparison with vaccinia virus. Journal of General Virology 73:2887–2902
    [Google Scholar]
  3. Alcamí A., Koszinowski U. H. 2000; Viral mechanisms of immune evasion. Immunology Today 21:447–455
    [Google Scholar]
  4. 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]
  5. 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]
  6. 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]
  7. 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]
  8. Bugert J. J., Darai G. 2000; Poxvirus homologues of cellular genes. Virus Genes 21:113–133
    [Google Scholar]
  9. Buller R. M., Palumbo G. J. 1991; Poxvirus pathogenesis. Microbiological Reviews 55:80–122
    [Google Scholar]
  10. Chensue S. W., Ward P. A. 1996; Inflammation. In Anderson’s Pathology pp 387–415 Edited by Damjanov I., Linder J. St Louis: Mosby;
    [Google Scholar]
  11. Comeau M. R., Johnson R., DuBose R. F., Petersen M., Gearing P., VandenBos T., Park L., Farrah T., Buller R. M., Cohen J. I., Strockbine L. D., Rauch C., Spriggs M. K. 1998; A poxvirus-encoded semaphorin induces cytokine production from monocytes and binds to a novel cellular semaphorin receptor, VESPR. Immunity 8:473–482
    [Google Scholar]
  12. Delaire S., Billard C., Tordjman R., Chédotal A., Elhabazi A., Bensussan A., Boumsell L. II 2001; Biological activity of soluble CD100. Soluble CD100, similarly to H-semaIII, inhibits immune cell migration. Journal of Immunology 166:4348–4354
    [Google Scholar]
  13. Engelstad M., Howard S. T., Smith G. L. 1992; A constitutively expressed vaccinia gene encodes a 42-kDa glycoprotein related to complement control factors that forms part of the extracellular virus envelope. Virology 188:801–810
    [Google Scholar]
  14. Ensser A., Fleckenstein B. 1995; Alcelaphine herpesvirus type 1 has a semaphorin-like gene. Journal of General Virology 76:1063–1067
    [Google Scholar]
  15. Esposito J., Condit R., Obijeski J. 1981; The preparation of orthopoxvirus DNA. Journal of Virological Methods 2:175–179
    [Google Scholar]
  16. Fleming P., Davis-Poynter N., Degli-Esposti M., Densley E., Papadimitriou J., Shellam G., Farrell H. 1999; The murine cytomegalovirus chemokine homolog, m131/129, is a determinant of viral pathogenicity. Journal of Virology 73:6800–6809
    [Google Scholar]
  17. Frank I., Stoiber H., Godar S., Stockinger H., Steindl F., Katinger H. W., Dierich M. P. 1996; Acquisition of host cell-surface-derived molecules by HIV-1. AIDS 10:1611–1620
    [Google Scholar]
  18. Goebel S. J., Johnson G. P., Perkus M. E., Davis S. W., Winslow J. P., Paoletti E. 1990; The complete DNA sequence of vaccinia virus. Virology 179:247–266, 517–563
    [Google Scholar]
  19. Hall K. T., Boumsell L., Schultze J. L., Boussiotis V. A., Dorfman D. M., Cardoso A. A., Bensussan A., Nadler L. M., Freeman G. J. 1996; Human CD100, a novel leukocyte semaphorin that promotes B-cell aggregation and differentiation. Proceedings of the National Academy of Sciences, USA 93:11780–11785
    [Google Scholar]
  20. Harlow E., Lane D. 1988 Antibodies: A Laboratory Manual. Cold Spring Harbor NY: Cold Spring Harbor Laboratory Press;
    [Google Scholar]
  21. 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. Journal of Biological Chemistry 266:20103–20109
    [Google Scholar]
  22. International Human Genome Sequencing Consortium 2001; Initial sequencing and analysis of the human genome. Nature 409:860–921
    [Google Scholar]
  23. Jin Q., Hou Y. D., Cheng N. H., Yao E. M., Cheng S. X., Yang X. K., Jing D. Y., Yu W. H., Yuan J. S., Ma X. J. 1998; Complete genomic sequence of vaccinia virus (Tian Tan strain). Genbank accession no. NC 002170
  24. Kolodkin A. L., Matthes D. J., Goodman C. S. 1993; The semaphorin genes encode a family of transmembrane and secreted growth cone guidance molecules. Cell 75:1389–1399
    [Google Scholar]
  25. Kumanogoh A., Watanabe C., Lee I., Wang X., Shi W., Araki H., Hirata H., Iwahori K., Uchida J., Yasui T., Matsumoto M., Yoshida K., Yakura H., Pan C., Parnes J. R., Kikutani H. 2000; Identification of CD72 as a lymphocyte receptor for the class IV semaphorin CD100. A novel mechanism for regulating B cell signaling. Immunity 13:621–631
    [Google Scholar]
  26. Laemmli U. K. 1970; Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227:680–685
    [Google Scholar]
  27. Lange C., Liehr T., Goen M., Gebhart E., Fleckenstein B., Ensser A. 1998; New eukaryotic semaphorins with close homology to semaphorins of DNA viruses. Genomics 51:340–350
    [Google Scholar]
  28. Massung R. F., Liu L. I., Qi J., Knight J. C., Yuran T. E., Kerlavage A. R., Parsons J. M., Venter J. C., Esposito J. J. 1994; Analysis of the complete genome of smallpox variola major virus strain Bangladesh-1975. Virology 201:215–240
    [Google Scholar]
  29. 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 erratum 3490
    [Google Scholar]
  30. Nakamura F., Kalb R. G., Strittmatter S. M. 2000; Molecular basis of semaphorin-mediated axon guidance. Journal of Neurobiology 44:219–229
    [Google Scholar]
  31. Ng A., Tscharke D. C., Reading P., 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]
  32. Penfold M. E., Dairaghi D. J., Duke G. M., Saederup N., Mocarski E. S., Kemble G. W., Schall T. J. 1999; Cytomegalovirus encodes a potent alpha chemokine. Proceedings of the National Academy of Sciences, USA 96:9839–9844
    [Google Scholar]
  33. Saederup N., Lin Y. C., Dairaghi D. J., Schall T. J., Mocarski E. S. 1999; Cytomegalovirus-encoded beta chemokine promotes monocyte-associated viremia in the host. Proceedings of the National Academy of Sciences, USA 96:10881–10886
    [Google Scholar]
  34. Sambrook J., Fritsch E. F., Maniatis T. 1989 Molecular Cloning. A Laboratory Manual, 2nd edn. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press;
  35. Schmelz M., Sodeik B., Ericsson M., Wolffe E. J., Shida H., Hiller G., Griffiths G. 1994; Assembly of vaccinia virus: the second wrapping cisterna is derived from the trans Golgi network. Journal of Virology 68:130–147
    [Google Scholar]
  36. Semaphorin Nomenclature Committee. 1999; Unified nomenclature for the semaphorins/collapsins. Cell 97:551–552
    [Google Scholar]
  37. Shchelkunov S. N., Resenchuk S. M., Totmenin A. V., Blinov V. M., Marennikova S. S., Sandakhchiev L. S. 1993; Comparison of the genetic maps of variola and vaccinia viruses. FEBS Letters 327:321–324
    [Google Scholar]
  38. Shchelkunov S. N., Totmenin A. V., Loparev V. N., Safronov P. F., Gutorov V. V., Chizhikov V. E., Knight J. C., Parsons J. M., Massung R. F., Esposito J. J. 2000; Alastrim smallpox variola minor virus genome DNA sequences. Virology 266:361–386
    [Google Scholar]
  39. Shi W., Kumanogoh A., Watanabe C., Uchida J., Wang X., Yasui T., Yukawa K., Ikawa M., Okabe M., Parnes J. R., Yoshida K., Kikutani H. 2000; The class IV semaphorin CD100 plays nonredundant roles in the immune system. Defective B and T cell activation in CD100-deficient mice. Immunity 13:633–642
    [Google Scholar]
  40. Smith G. L. 1993; Expression of genes by vaccinia virus vectors. In Molecular Virology: A Practical Approach pp 257–283 Edited by Davison A. J., Elliott R. Oxford: Oxford University Press;
    [Google Scholar]
  41. Smith G. L. 2000; Secreted poxvirus proteins that interact with the immune system. In Effects of Microbes on the Immune System pp 491–507 Edited by Cunningham M. W., Fujinami R. S. Philadelphia: Lippincott Williams & Wilkins;
    [Google Scholar]
  42. Smith G. L., Chan Y. S., Howard S. T. 1991; Nucleotide sequence of 42 kbp of vaccinia virus strain WR from near the right inverted terminal repeat. Journal of General Virology 72:1349–1376
    [Google Scholar]
  43. Smith G. L., Symons J. A., Khanna A., Vanderplasschen A., Alcamí A. 1997; Vaccinia virus immune evasion. Immunological Reviews 159:137–154
    [Google Scholar]
  44. Spriggs M. K. 1999; Shared resources between the neural and immune systems: semaphorins join the ranks. Current Opinion in Immunology 11:387–391
    [Google Scholar]
  45. Spriggs M. K., Hruby D. E., Maliszewski C. R., Pickup D. J., Sims J. E., Buller R. M., VanSlyke J. 1992; Vaccinia and cowpox viruses encode a novel secreted interleukin-1-binding protein. Cell 71:145–152
    [Google Scholar]
  46. Tamagnone L., Comoglio P. M. 2000; Signalling by semaphorin receptors: cell guidance and beyond. Trends in Cell Biology 10:377–383
    [Google Scholar]
  47. Tamagnone L., Artigiani S., Chen H., He Z., Ming G. I., Song H., Chedotal A., Winberg M. L., Goodman C. S., Poo M., Tessier-Lavigne M., Comoglio P. M. 1999; Plexins are a large family of receptors for transmembrane, secreted, and GPI-anchored semaphorins in vertebrates. Cell 99:71–80
    [Google Scholar]
  48. Tortorella D., Gewurz B. E., Furman M. H., Schust D. J., Ploegh H. L. 2000; Viral subversion of the immune system. Annual Review of Immunology 18:861–926
    [Google Scholar]
  49. Tscharke D. C., Smith G. L. 1999; A model for vaccinia virus pathogenesis and immunity based on intradermal injection of mouse ear pinnae. Journal of General Virology 80:2751–2755
    [Google Scholar]
  50. Van Vactor D. V., Lorenz L. J. 1999; Neural development: the semantics of axon guidance. Current Biology 9:R201–R204
    [Google Scholar]
  51. Venter J. C., Adams M. D., Myers E. W., Li P. W., Mural R. J., Sutton G. G., Smith H. O., Yandell M., Evans C. A., Holt R. A., Gocayne J. D., Amanatides P., Ballew R. M., Huson D. H., Wortman J. R., Zhang Q., Kodira C. D., Zheng X. H., Chen L., Skupski M., Subramanian G., Thomas P. D., Zhang J., Gabor Miklos G. L., Nelson C., Broder S., Clark A. G., Nadeau J., McKusick V. A., Zinder N., Levine A. J., Roberts R. J., Simon M., Slayman C., Hunkapiller M., Bolanos R., Delcher A., Dew I., Fasulo D., Flanigan M., Florea L., Halpern A., Hannenhalli S., Kravitz S., Levy S., Mobarry C., Reinert K., Remington K., Abu-Threideh J., Beasley E., Biddick K., Bonazzi V., Brandon R., Cargill M., Chandramouliswaran I., Charlab R., Chaturvedi K., Deng Z., Di Francesco V., Dunn P., Eilbeck K., Evangelista C., Gabrielian A. E., Gan W., Ge W., Gong F., Gu Z., Guan P., Heiman T. J., Higgins M. E., Ji R. R., Ke Z., Ketchum K. A., Lai Z., Lei Y., Li Z., Li J., Liang Y., Lin X., Lu F., Merkulov G. V., Milshina N., Moore H. M., Naik A. K., Narayan V. A., Neelam B., Nusskern D., Rusch D. B., Salzberg S., Shao W., Shue B., Sun J., Wang Z., Wang A., Wang X., Wang J., Wei M., Wides R., Xiao C., Yan C. and others 2001; The sequence of the human genome. Science 291:1304–1351
    [Google Scholar]
  52. Xu X., Ng S., Wu Z. L., Nguyen D., Homburger S., Seidel-Dugan C., Ebens A., Luo Y. 1998; Human semaphorin K1 is glycosylphosphatidylinositol-linked and defines a new subfamily of viral-related semaphorins. Journal of Biological Chemistry 273:22428–22434
    [Google Scholar]
  53. Yamada A., Kubo K., Takeshita A., Harashima N., Kawano K., Mine T., Sagawa K., Sugamura K., Itoh K. 1999; Molecular cloning of a glycosylphosphatidylinositol-anchored molecule CDw108. Journal of Immunology 162:4094–4100
    [Google Scholar]
  54. Zou P., Isegawa Y., Nakano K., Haque M., Horiguchi Y., Yamanishi K. 1999; Human herpesvirus 6 open reading frame U83 encodes a functional chemokine. Journal of Virology 73:5926–5933
    [Google Scholar]
/content/journal/jgv/10.1099/0022-1317-82-9-2083
Loading
/content/journal/jgv/10.1099/0022-1317-82-9-2083
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