1887

Abstract

Chordate poxviruses encode several uncharacterized POZ-kelch proteins and three of these are present in (VV) strain Western Reserve. VV gene is predicted to encode a protein of 512 amino acid residues with a POZ/BTB domain in the N-terminal region and three kelch motifs in the C-terminal half of the protein. We have identified the C2L gene product as an intracellular protein of 56 kDa and constructed and characterized a VV mutant lacking the gene (vΔC2L). Compared to wild-type and revertant viruses, vΔC2L had unaltered growth , but had a different plaque morphology due to an altered cytopathic effect (CPE) of infected cells. Deleting had no effect on VV-induced formation of actin tails or enhanced cell motility, but affected the development of VV-induced cellular projections and the Ca-independent cell/extracellular matrix adhesion late during infection. In an intranasal mouse model, C2L did not contribute to virus virulence. However, in an intradermal mouse model, infection with vΔC2L resulted in larger lesions and more cell infiltration into the infected ears during recovery from infection. Thus, in this model, C2L protein inhibits inflammation and reduces immunopathology. In summary, we found that C2L is not required for virus replication but contributes to aspects of VV-induced CPE and reduces immunopathology .

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2003-09-01
2024-04-18
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References

  1. Adams J., Kelso R., Cooley L. 2000; The kelch repeat superfamily of proteins: propellers of cell function. Trends Cell Biol 10:17–24
    [Google Scholar]
  2. Ahmad K. F., Engel C. K., Prive G. G. 1998; Crystal structure of the BTB domain from PLZF. Proc Natl Acad Sci U S A 95:12123–12128
    [Google Scholar]
  3. Appleyard G., Hapel A. J., Boulter E. A. 1971; An antigenic difference between intracellular and extracellular rabbitpox virus. J Gen Virol 13:9–17
    [Google Scholar]
  4. Bablanian R., Baxt B., Sonnabend J. A., Esteban M. 1978; Studies on the mechanisms of vaccinia virus cytopathic effects. II. Early cell rounding is associated with virus polypeptide synthesis. J Gen Virol 39:403–413
    [Google Scholar]
  5. Bardwell V. J., Treisman R. 1994; The POZ domain: a conserved protein–protein interaction motif. Genes Dev 8:1664–1677
    [Google Scholar]
  6. Bartlett N., Symons J. A., Tscharke D. C., Smith G. L. 2002; The vaccinia virus N1L protein is an intracellular homodimer that promotes virulence. J Gen Virol 83:1965–1976
    [Google Scholar]
  7. Bork P., Doolittle R. F. 1994; Drosophila kelch motif is derived from a common enzyme fold. J Mol Biol 236:1277–1282
    [Google Scholar]
  8. Buller R. M., Palumbo G. J. 1991; Poxvirus pathogenesis. Microbiol Rev 55:80–122
    [Google Scholar]
  9. Carter G., Rodger G., Murphy B. J., Law M., Krauss O., Hollinshead M., Smith G. L. 2003; Vaccinia virus cores are transported on microtubules. J Gen Virol 84:2443–2458
    [Google Scholar]
  10. Cudmore S., Cossart P., Griffiths G., Way M. 1995; Actin-based motility of vaccinia virus. Nature 378:636–638
    [Google Scholar]
  11. Esposito J., Condit R., Obijeski J. 1981; The preparation of orthopoxvirus DNA. J Virol Methods 2:175–179
    [Google Scholar]
  12. Falkner F. G., Moss B. 1990; Transient dominant selection of recombinant vaccinia viruses. J Virol 64:3108–3111
    [Google Scholar]
  13. Geiger B., Bershadsky A., Pankov R., Yamada K. M. 2001; Transmembrane crosstalk between the extracellular matrix and the cytoskeleton. Nat Rev Mol Cell Biol 2:793–805
    [Google Scholar]
  14. 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]
  15. Hiller G., Weber K., Schneider L., Parajsz C., Jungwirth C. 1979; Interaction of assembled progeny pox viruses with the cellular cytoskeleton. Virology 98:142–153
    [Google Scholar]
  16. Hollinshead M., Rodger G., Van Eijl H., Law M., Hollinshead R., Vaux D. J., Smith G. L. 2001; Vaccinia virus utilizes microtubules for movement to the cell surface. J Cell Biol 154:389–402
    [Google Scholar]
  17. 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]
  18. Hynes R. O. 1992; Integrins: versatility, modulation, and signaling in cell adhesion. Cell 69:11–25
    [Google Scholar]
  19. Kotwal G. J., Moss B. 1988; Analysis of a large cluster of nonessential genes deleted from a vaccinia virus terminal transposition mutant. Virology 167:524–537
    [Google Scholar]
  20. Lallier T., Bronner-Fraser M. 1992; Alpha 1 beta 1 integrin on neural crest cells recognizes some laminin substrata in a Ca2+-independent manner. J Cell Biol 119:1335–1345
    [Google Scholar]
  21. Law M., Hollinshead R., Smith G. L. 2002; Antibody-sensitive and antibody-resistant cell-to-cell spread by vaccinia virus: role of the A33R protein in antibody-resistant spread. J Gen Virol 83:209–222
    [Google Scholar]
  22. Locker J. K., Kuehn A., Schleich S., Rutter G., Hohenberg H., Wepf R., Griffiths G. 2000; Entry of the two infectious forms of vaccinia virus at the plasma membrane is signaling-dependent for the IMV but not the EEV. Mol Biol Cell 11:2497–2511
    [Google Scholar]
  23. Mallardo M., Schleich S., Krijnse Locker J. 2001; Microtubule-dependent organization of vaccinia virus core-derived early mRNAs into distinct cytoplasmic structures. Mol Biol Cell 12:3875–3891
    [Google Scholar]
  24. Moss B. 2001; Poxviridae : the viruses and their replication. In Fields Virology , 4th edn. pp  2849–2883 Edited by Knipe D. M., Howley P. M. Philadelphia: Lippincott Williams & Wilkins;
    [Google Scholar]
  25. Mould A. P. 1996; Getting integrins into shape: recent insights into how integrin activity is regulated by conformational changes. J Cell Sci 109:2613–2618
    [Google Scholar]
  26. 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. J Gen Virol 82:2095–2105
    [Google Scholar]
  27. 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
    [Google Scholar]
  28. Payne L. G. 1980; Significance of extracellular enveloped virus in the in vitro and in vivo dissemination of vaccinia. J Gen Virol 50:89–100
    [Google Scholar]
  29. Perkus M. E., Goebel S. J., Davis S. W., Johnson G. P., Norton E. K., Paoletti E. 1991; Deletion of 55 open reading frames from the termini of vaccinia virus. Virology 180:406–410
    [Google Scholar]
  30. Petit V., Thiery J. P. 2000; Focal adhesions: structure and dynamics. Biol Cell 92:477–494
    [Google Scholar]
  31. Ploubidou A., Moreau V., Ashman K., Reckmann I., Gonzalez C., Way M. 2000; Vaccinia virus infection disrupts microtubule organization and centrosome function. EMBO J 19:3932–3944
    [Google Scholar]
  32. Rietdorf J., Ploubidou A., Reckmann I., Holmstrom A., Frischknecht F., Zettl M., Zimmermann T., Way M. 2001; Kinesin-dependent movement on microtubules precedes actin-based motility of vaccinia virus. Nat Cell Biol 3:992–1000
    [Google Scholar]
  33. Rodger G., Smith G. L. 2002; Replacing the SCR domains of vaccinia virus protein B5R with EGFP causes a reduction in plaque size and actin tail formation but enveloped virions are still transported to the cell surface. J Gen Virol 83:323–332
    [Google Scholar]
  34. Sanderson C. M., Smith G. L. 1998; Vaccinia virus induces Ca2+-independent cell-matrix adhesion during the motile phase of infection. J Virol 72:9924–9933
    [Google Scholar]
  35. Sanderson C. M., Way M., Smith G. L. 1998; Virus-induced cell motility. J Virol 72:1235–1243
    [Google Scholar]
  36. Sanderson C. M., Hollinshead M., Smith G. L. 2000; The vaccinia virus A27L protein is needed for the microtubule-dependent transport of intracellular mature virus particles. J Gen Virol 81:47–58
    [Google Scholar]
  37. Shchelkunov S., Totmenin A., Kolosova I. 2002; Species-specific differences in organization of orthopoxvirus kelch-like proteins. Virus Genes 24:157–162
    [Google Scholar]
  38. Smith G. L. 1995; 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]
  39. Smith G. L., Levin J. Z., Palese P., Moss B. 1987; Synthesis and cellular location of the ten influenza polypeptides individually expressed by recombinant vaccinia viruses. Virology 160:336–345 erratum 163:259
    [Google Scholar]
  40. Smith G. L., Vanderplasschen A., Law M. 2002; The formation and function of extracellular enveloped vaccinia virus. J Gen Virol 83:2915–2931
    [Google Scholar]
  41. 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]
  42. 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]
  43. van Eijl H., Hollinshead M., Rodger G., Zhang W. H., Smith G. L. 2002; The vaccinia virus F12L protein is associated with intracellular enveloped virus particles and is required for their egress to the cell surface. J Gen Virol 83:195–207
    [Google Scholar]
  44. Ward B. M., Moss B. 2001; Vaccinia virus intracellular movement is associated with microtubules and independent of actin tails. J Virol 75:11651–11663
    [Google Scholar]
  45. Xue F., Cooley L. 1993; Kelch encodes a component of intercellular bridges in Drosophila egg chambers. Cell 72:681–693
    [Google Scholar]
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