1887

Abstract

We have characterized a novel, captured and fully functional viral interleukin (IL)-10 homologue (IL-10) from the gammaherpesvirus ovine herpesvirus 2. Unlike IL-10 homologues from other gammaherpesviruses, the IL-10 peptide sequence was highly divergent from that of the host species. The IL-10 gene is unique amongst virus captured genes in that it has precisely retained the original cellular exon structure, having five exons of similar sizes to the cellular counterparts. However, the sizes of the introns are dramatically reduced. The IL-10 protein was shown to be a non-glycosylated, secreted protein of 21 000 with a signal peptidase cleavage site between amino acids 26 and 27 of the nascent peptide. Functional assays showed that IL-10, in a similar way to ovine IL-10, stimulated mast cell proliferation and inhibited macrophage inflammatory chemokine production. This is the first example of a captured herpesvirus gene retaining the full cellular gene structure.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.2008/001743-0
2008-10-01
2024-12-06
Loading full text...

Full text loading...

/deliver/fulltext/jgv/89/10/2447.html?itemId=/content/journal/jgv/10.1099/vir.0.2008/001743-0&mimeType=html&fmt=ahah

References

  1. Altschul S. F., Gish W., Miller W., Myers E. W., Lipman D. J. 1990; Basic local alignment search tool. J Mol Biol 215:403–410 [CrossRef]
    [Google Scholar]
  2. Baxter S. I., Pow I., Bridgen A., Reid H. W. 1993; PCR detection of the sheep-associated agent of malignant catarrhal fever. Arch Virol 132:145–159 [CrossRef]
    [Google Scholar]
  3. Brunovskis P., Kung H. J. 1995; Retrotransposition and herpesvirus evolution. Virus Genes 11:259–270 [CrossRef]
    [Google Scholar]
  4. Bugert J. J., Darai G. 2000; Poxvirus homologues of cellular genes. Virus Genes 21:111–133 [CrossRef]
    [Google Scholar]
  5. Buxton D., Reid H. W., Finlayson J., Pow I., Berrie E. 1985; Transmission of a malignant catarrhal fever-like syndrome to sheep: preliminary experiments. Res Vet Sci 38:22–29
    [Google Scholar]
  6. Chaston T. B., Lidbury B. A. 2001; Genetic 'budget' of viruses and the cost to the infected host: a theory on the relationship between the genetic capacity of viruses, immune evasion, persistence and disease. Immunol Cell Biol 79:62–66 [CrossRef]
    [Google Scholar]
  7. Ding Y., Qin L., Kotenko S. V., Pestka S., Bromberg J. S. 2000; A single amino acid determines the immunostimulatory activity of interleukin 10. J Exp Med 191:213–224 [CrossRef]
    [Google Scholar]
  8. Edgar R. C. 2004; MUSCLE: a multiple sequence alignment method with reduced time and space complexity. BMC Bioinformatics 5:113 [CrossRef]
    [Google Scholar]
  9. Ehlers B., Dural G., Yasmum N., Lembo T., de Thoisy B., Ryser-Degiorgis M. P., Ulrich R. G., McGeoch D. J. 2008; Novel mammalian herpesviruses and lineages within the Gammaherpesvirinae: cospeciation and interspecies transfer. J Virol 82:3509–3516 [CrossRef]
    [Google Scholar]
  10. Emanuelsson O., Brunak S., von Heijne G., Nielsen H. 2007; Locating proteins in the cell using TargetP, SignalP and related tools. Nat Protoc 2:953–971 [CrossRef]
    [Google Scholar]
  11. Ensser A., Pflanz R., Fleckenstein B. 1997; Primary structure of the alcelaphine herpesvirus 1 genome. J Virol 71:6517–6525
    [Google Scholar]
  12. Entrican G., Wilkie R., McWaters P., Scheerlinck J., Wood P. R., Brown J. 1999; Cytokine release by ovine macrophages following infection with Chlamydia psittaci . Clin Exp Immunol 117:309–315 [CrossRef]
    [Google Scholar]
  13. Gulley M. L., Raphael M., Lutz C. T., Ross D. W., Raab-Traub N. 1992; Epstein-Barr virus integration in human lymphomas and lymphoid cell lines. Cancer 70:185–191 [CrossRef]
    [Google Scholar]
  14. Haig D. M., Hutchinson G., Thomson J., Yirrell D., Reid H. W. 1996; Cytolytic activity and associated serine protease expression by skin and afferent lymph CD8+ T cells during orf virus reinfection. J Gen Virol 77:953–961 [CrossRef]
    [Google Scholar]
  15. Haig D. M., Thomson J., McInnes C. J., Deane D. L., Anderson I. E., McCaughan C. A., Imlach W., Mercer A. A., Howard C. J., Fleming S. B. 2002; A comparison of the anti-inflammatory and immuno-stimulatory activities of orf virus and ovine interleukin-10. Virus Res 90:303–316 [CrossRef]
    [Google Scholar]
  16. Hart J., Ackermann M., Jayawardane G., Russell G., Haig D. M., Reid H., Stewart J. P. 2007; Complete sequence and analysis of the ovine herpesvirus 2 genome. J Gen Virol 88:28–39 [CrossRef]
    [Google Scholar]
  17. Henderson A., Ripley S., Heller M., Kieff E. 1983; Chromosome site for Epstein-Barr virus DNA in a Burkitt tumor cell line and in lymphocytes growth-transformed in vitro . Proc Natl Acad Sci U S A 80:1987–1991 [CrossRef]
    [Google Scholar]
  18. Holzerlandt R., Orengo C., Kellam P., Alba M. M. 2002; Identification of new herpesvirus gene homologs in the human genome. Genome Res 12:1739–1748 [CrossRef]
    [Google Scholar]
  19. Hughes A. L. 2002; Origin and evolution of viral interleukin-10 and other DNA virus genes with vertebrate homologues. J Mol Evol 54:90–101 [CrossRef]
    [Google Scholar]
  20. Jenkins C., Abendroth A., Slobedman B. 2004; A novel viral transcript with homology to human interleukin-10 is expressed during latent human cytomegalovirus infection. J Virol 78:1440–1447 [CrossRef]
    [Google Scholar]
  21. Jones B. C., Logsdon N. J., Josephson K., Cook J., Barry P. A., Walter M. R. 2002; Crystal structure of human cytomegalovirus IL-10 bound to soluble human IL-10R1. Proc Natl Acad Sci U S A 99:9404–9409 [CrossRef]
    [Google Scholar]
  22. Josephson K., Logsdon N. J., Walter M. R. 2001; Crystal structure of the IL-10/IL-10R1 complex reveals a shared receptor binding site. Immunity 15:35–46 [CrossRef]
    [Google Scholar]
  23. Josephson K., Jones B. C., Walter L. J., DiGiacomo R., Indelicato S. R., Walter M. R. 2002; Noncompetitive antibody neutralization of IL-10 revealed by protein engineering and X-ray crystallography. Structure 10:981–987 [CrossRef]
    [Google Scholar]
  24. Katoh K., Kuma K., Toh H., Miyata T. 2005; mafft version 5: improvement in accuracy of multiple sequence alignment. Nucleic Acids Res 33:511–518 [CrossRef]
    [Google Scholar]
  25. Kotenko S. V., Saccani S., Izotova L. S., Mirochnitchenko O. V., Pestka S. 2000; Human cytomegalovirus harbors its own unique IL-10 homolog (cmvIL-10. Proc Natl Acad Sci U S A 97:1695–1700 [CrossRef]
    [Google Scholar]
  26. Kurilla M. G., Swaminathan S., Welsh R. M., Kieff E., Brutkiewicz R. R. 1993; Effects of virally expressed interleukin-10 on vaccinia virus infection in mice. J Virol 67:7623–7628
    [Google Scholar]
  27. Lockridge K. M., Zhou S. S., Kravitz R. H., Johnson J. L., Sawai E. T., Blewett E. L., Barry P. A. 2000; Primate cytomegaloviruses encode and express an IL-10-like protein. Virology 268:272–280 [CrossRef]
    [Google Scholar]
  28. McGeoch D. J. 2001; Molecular evolution of the γ - Herpesvirinae . Philos Trans R Soc Lond B Biol Sci 356:421–435 [CrossRef]
    [Google Scholar]
  29. McGeoch D. J., Davison A. J. 1999; The descent of human herpesvirus 8. Semin Cancer Biol 9:201–209 [CrossRef]
    [Google Scholar]
  30. McGeoch D. J., Rixon F. J., Davison A. J. 2006; Topics in herpesvirus genomics and evolution. Virus Res 117:90–104 [CrossRef]
    [Google Scholar]
  31. Moore K. W., Vieira P., Fiorentino D. F., Trounstine M. L., Khan T. A., Mosmann T. R. 1990; Homology of cytokine synthesis inhibitory factor (IL-10) to the Epstein-Barr virus gene BCRFI. Science 248:1230–1234 [CrossRef]
    [Google Scholar]
  32. Mosmann T. R. 1994; Properties and functions of interleukin-10. Adv Immunol 56:1–26
    [Google Scholar]
  33. Norman J. A., Hobart P., Manthorpe M., Felgner P., Wheeler C. 1997; Development of improved vectors for DNA-based immunization and other gene therapy applications. Vaccine 15:801–803 [CrossRef]
    [Google Scholar]
  34. Notredame C., Suhre K. 2004; Computing multiple sequence/structure alignments with the T-coffee package. Curr Protoc Bioinformatics Chapter 3: Unit3 8
    [Google Scholar]
  35. Reid H. W., Buxton D. 1989; Malignant catarrhal fever and the gammaherpesvirinae of Bovidae. In Herpesvirus Diseases of Cattle, Horses and Pigs pp 116–162Edited by Wittman G. London: Kluwer Academic;
    [Google Scholar]
  36. Rode H. J., Janssen W., Rosen-Wolff A., Bugert J. J., Thein P., Becker Y., Darai G. 1993; The genome of equine herpesvirus type 2 harbors an interleukin 10 (IL10)-like gene. Virus Genes 7:111–116 [CrossRef]
    [Google Scholar]
  37. Ronquist F., Huelsenbeck J. P. 2003; MrBayes 3: Bayesian phylogenetic inference under mixed models. Bioinformatics 19:1572–1574 [CrossRef]
    [Google Scholar]
  38. Sambrook J., Fritsch E. F., Maniatis T. 1989 Molecular Cloning: a Laboratory Manual, 2nd edn. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory;
    [Google Scholar]
  39. Schlaak J. F., Schmitt E., Huls C., , Meyer zum Buschenfelde K. H., Fleischer B. 1994; A sensitive and specific bioassay for the detection of human interleukin-10. J Immunol Methods 168:49–54 [CrossRef]
    [Google Scholar]
  40. Shackelton L. A., Holmes E. C. 2004; The evolution of large DNA viruses: combining genomic information of viruses and their hosts. Trends Microbiol 12:458–465 [CrossRef]
    [Google Scholar]
  41. Stewart J. P., Rooney C. M. 1992; The interleukin-10 homolog encoded by Epstein-Barr virus enhances the reactivation of virus-specific cytotoxic T cell and HLA-unrestricted killer cell responses. Virology 191:773–782 [CrossRef]
    [Google Scholar]
  42. Stewart J. P., Janjua N. J., Pepper S. D., Bennion G., Mackett M., Allen T., Nash A. A., Arrand J. R. 1996; Identification and characterization of murine gammaherpesvirus 68 gp150: a virion membrane glycoprotein. J Virol 70:3528–3535
    [Google Scholar]
  43. Taus N. S., Herndon D. R., Traul D. L., Stewart J. P., Ackermann M., Li H., Knowles D. P., Lewis G. S., Brayton K. A. 2007; Comparison of ovine herpesvirus 2 genomes isolated from domestic sheep ( Ovis aries ) and a clinically affected cow ( Bos bovis ). J Gen Virol 88:40–45 [CrossRef]
    [Google Scholar]
  44. Thompson J. D., Higgins D. G., Gibson T. J. 1994; clustal w: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. Nucleic Acids Res 22:4673–4680 [CrossRef]
    [Google Scholar]
  45. Thonur L., Russell G. C., Stewart J. P., Haig D. M. 2006; Differential transcription of ovine herpesvirus 2 genes in lymphocytes from reservoir and susceptible species. Virus Genes 32:27–35 [CrossRef]
    [Google Scholar]
  46. Walter M. R., Nagabhushan T. L. 1995; Crystal structure of interleukin 10 reveals an interferon gamma-like fold. Biochemistry 34:12118–12125 [CrossRef]
    [Google Scholar]
  47. Yang Z. 2007; PAML 4: phylogenetic analysis by maximum likelihood. Mol Biol Evol 24:1586–1591 [CrossRef]
    [Google Scholar]
  48. Zdanov A., Schalk-Hihi C., Menon S., Moore K. W., Wlodawer A. 1997; Crystal structure of Epstein-Barr virus protein BCRF1, a homolog of cellular interleukin-10. J Mol Biol 268:460–467 [CrossRef]
    [Google Scholar]
/content/journal/jgv/10.1099/vir.0.2008/001743-0
Loading
/content/journal/jgv/10.1099/vir.0.2008/001743-0
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