1887

Abstract

The sheep parapoxvirus orf virus (ORFV) induces acute, pustular skin lesions in humans. ORFV encodes an orthologue of interleukin-10 (IL-10) that, whilst it closely resembles ovine IL-10 (91 % amino acid identity), shows only 75 % amino acid identity to human IL-10 (hIL-10). The anti-inflammatory potential of ORFV IL-10 in human ORFV infection was investigated by examining its immunosuppressive effects on THP-1 monocytes. ORFV IL-10 and hIL-10 were shown to have equivalent inhibitory effects on the synthesis of proinflammatory cytokines in lipopolysaccharide-activated monocytes, but differed in their abilities to inhibit monocyte proliferation. Structural modelling of ORFV IL-10 revealed differences from hIL-10 in residues predicted to interact with IL-10 co-receptor 2 (IL-10R2), whereas there were very few differences in the residues predicted to interact with IL-10R1. These findings suggest that the partial ability of ORFV IL-10 to inhibit THP-1 monocyte proliferation may be due to the absence of critical residues that mediate the interaction with human IL-10R2.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.82765-0
2007-06-01
2020-01-18
Loading full text...

Full text loading...

/deliver/fulltext/jgv/88/6/1677.html?itemId=/content/journal/jgv/10.1099/vir.0.82765-0&mimeType=html&fmt=ahah

References

  1. Cassatella, M. A., Tamassia, N., Crepaldi, L., McDonald, P. P., Ear, T., Calzetti, F., Gasperini, S., Zanderigo, F. & Bazzoni, F. ( 2005; ). Lipopolysaccharide primes neutrophils for a rapid response to IL-10. Eur J Immunol 35, 1877–1885.[CrossRef]
    [Google Scholar]
  2. Chan, A., Baird, M., Mercer, A. A. & Fleming, S. B. ( 2006; ). Maturation and function of human dendritic cells are inhibited by orf virus-encoded interleukin-10. J Gen Virol 87, 3177–3181.[CrossRef]
    [Google Scholar]
  3. Crepaldi, L., Gasperini, S., Lapinet, J. A., Calzetti, F., Pinardi, C., Liu, Y., Zurawski, S., de Waal Malefyte, R., Moore, K. W. & Cassatella, M. A. ( 2001; ). Upregulation of IL-10R1 expression is required to render human neutrophils fully responsive to IL-10. J Immunol 167, 2312–2322.[CrossRef]
    [Google Scholar]
  4. Deane, D.,, McInnes, C. J., Percival, A., Wood, A., Thomson, J., Lear, A., Gilray, J., Fleming, S., Mercer, A. & Haig, D. ( 2000; ). Orf virus encodes a novel secreted protein inhibitor of granulocyte-macrophage colony stimulating factor and interleukin-2. J Virol 74, 1313–1320.[CrossRef]
    [Google Scholar]
  5. Ding, Y., Qin, L., Zamarin, D., Kotenko, S., Pestka, S., Moore, K. W. & Bromberg, J. S. ( 2001; ). Differential IL-10R1 expression plays a critical role in IL-10-mediated immune regulation. J Immunol 167, 6884–6892.[CrossRef]
    [Google Scholar]
  6. Fleming, S. B., McCaughan, C. A., Andrews, A. E., Nash, A. D. & Mercer, A. A. ( 1997; ). A homolog of interleukin-10 is encoded by the poxvirus orf virus. J Virol 71, 4857–4861.
    [Google Scholar]
  7. Guex, N. & Peitsch, M. C. ( 1997; ). swiss-model and the SwissPdbViewer: an environment for comparative protein modeling. Electrophoresis 18, 2714–2723.[CrossRef]
    [Google Scholar]
  8. Haig, D. M. & McInnes, C. J. ( 2002; ). Immunity and counterimmunity during infection with the parapoxvirus orf virus. Virus Res 88, 3–16.[CrossRef]
    [Google Scholar]
  9. Haig, D. M., Thomson, J., McInnes, C., McCaughan, C., Imlach, W., Mercer, A. & Fleming, S. ( 2002a; ). Orf virus immuno-modulation and the host immune response. Vet Immunol Immunopathol 87, 395–399.[CrossRef]
    [Google Scholar]
  10. 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. ( 2002b; ). A comparison of the anti-inflammatory and immunostimulatory activities of orf virus and ovine interleukin-10. Virus Res 90, 303–316.[CrossRef]
    [Google Scholar]
  11. Imlach, W., McCaughan, C. A., Mercer, A. A., Haig, D. & Fleming, S. B. ( 2002; ). Orf virus encoded interleukin-10 stimulates the proliferation of murine mast cells and inhibits cytokine synthesis in murine peritoneal macrophages. J Gen Virol 83, 1049–1058.
    [Google Scholar]
  12. Josephson, K., Logsdon, N. J. & Walter, M. ( 2001; ). Crystal structure of the IL-10/IL-10R1 complex reveals a shared receptor binding site. Immunity 15, 35–46.[CrossRef]
    [Google Scholar]
  13. Kotenko, S. V., Krause, C. D., Isotova, L. S., Pollack, B. P., Wu, W. & Pestka, S. ( 1997; ). Identification and functional characterisation of a second chain of the interleukin-10 receptor complex. EMBO J 16, 5894–5903.[CrossRef]
    [Google Scholar]
  14. Lateef, Z., Fleming, S. B., Halliday, G., Faulkner, L., Mercer, A. & Baird, M. ( 2003; ). Orf virus-encoded interleukin-10 inhibits maturation, antigen presentation and migration of murine dendritic cells. J Gen Virol 84, 1101–1109.[CrossRef]
    [Google Scholar]
  15. Moore, K. W., de Waal Malefyte, R., Coffman, R. L. & O'Garra, A. ( 2001; ). Interleukin-10 and the interleukin-10 receptor. Annu Rev Immunol 19, 683–765.[CrossRef]
    [Google Scholar]
  16. Murray, P. J. ( 2006; ). Stat3-mediated anti-inflammatory signalling. Biochem Soc Trans 34, 1028–1031.[CrossRef]
    [Google Scholar]
  17. O'Farrell, A. M., Liu, Y., Moore, K. W. & Mui, A. L. ( 1998; ). IL-10 inhibits macrophage activation and proliferation by distinct signalling mechanisms: evidence for Stat3-dependent and -independent pathways. EMBO J 17, 1006–1018.[CrossRef]
    [Google Scholar]
  18. O'Farrell, A. M., Parry, D. A., Zindy, F., Roussel, M. F., Lees, E., Moore, K. W. & Mui, A. L. ( 2000; ). Stat3-dependent induction of p19INK4D by IL-10 contributes to inhibition of macrophage proliferation. J Immunol 164, 4607–4615.[CrossRef]
    [Google Scholar]
  19. PE Applied Biosystems ( 1997; ). ABI PRISM 7700 Sequence Detection System (User Bulletin #2). Foster City, CA: Perkin-Elmer Corporation.
  20. Pletnev, S., Magracheva, E., Wlodawer, A. & Zdanov, A. ( 2005; ). A model of the ternary complex of interleukin-10 with its soluble receptors. BMC Struct Biol 5, 10 [CrossRef]
    [Google Scholar]
  21. Qasimi, P., Ming-Lum, A., Ghanipour, A., Ong, C. J., Cox, M. E., Ihle, J., Cacalano, N., Yoshimura, A. & Mui, A. L. ( 2006; ). Divergent mechanisms utilized by SOCS3 to mediate interleukin-10 inhibition of tumor necrosis factor alpha and nitric oxide production by macrophages. J Biol Chem 281, 6316–6324.[CrossRef]
    [Google Scholar]
  22. Spencer, S. D., Di Marco, F., Hooley, J., Pitts-Meek, S., Bauer, M., Ryan, A. M., Sordat, B., Gibbs, V. C. & Aguet, M. ( 1998; ). The orphan receptor CRF2-4 is an essential subunit of the interleukin 10 receptor. J Exp Med 187, 571–578.[CrossRef]
    [Google Scholar]
  23. Usacheva, A., Kotenko, S., Witte, M. M. & Colamonici, O. R. ( 2002; ). Two distinct domains within the N-terminal region of Janus kinase 1 interact with cytokine receptors. J Immunol 169, 1302–1308.[CrossRef]
    [Google Scholar]
  24. Williams, L., Bradley, L., Smith, A. & Foxwell, B. ( 2004; ). Signal transducer and activator of transcription 3 is the dominant mediator of the anti-inflammatory effects of IL-10 in human macrophages. J Immunol 172, 567–576.[CrossRef]
    [Google Scholar]
  25. Yoon, S. I., Logsdon, N. J., Sheikh, F., Donnelly, R. P. & Walter, M. R. ( 2006; ). Conformational changes mediate IL-10R2 binding to IL-10 and assembly of the signalling complex. J Biol Chem 281, 35088–35096.[CrossRef]
    [Google Scholar]
  26. Zdanov, A., Schalk-Hihi, C. & Wlodawer, A. ( 1996; ). Crystal structure of human interleukin-10 at 1.6 Å resolution and model of a complex with its soluble receptor. Protein Sci 5, 1955–1962.[CrossRef]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.82765-0
Loading
/content/journal/jgv/10.1099/vir.0.82765-0
Loading

Data & Media loading...

Supplements

vol. , part 6, pp. 1677 – 1682

Effects of ORFV IL-10 on cytokine synthesis at the protein and transcriptional level in LPS-activated THP-1 monocytes

IL-10R1 expression is upregulated in THP-1 cells by LPS

Effects of ORFV IL-10 on THP-1 monocyte proliferation

[ Single PDF file] (137 KB)



PDF

Most cited articles

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