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A comparison of the anti-inflammatory and immuno-stimulatory activities of orf virus and ovine interleukin-10

2002; Elsevier BV; Volume: 90; Issue: 1-2 Linguagem: Inglês

10.1016/s0168-1702(02)00252-6

1872-7492

David M. Haig, Jacqueline Thomson, Colin J. McInnes, David Deane, I.E. Anderson, Catherine A. McCaughan, Wendy L. Imlach, Andrew A. Mercer, Chris Howard, Stephen B. Fleming,

Virus-based gene therapy research

Orf virus causes pustular skin lesions (orf) in sheep, goats and humans. The virus encodes an interleukin-10 (orfvIL-10) that is identical in amino acid composition to ovine IL-10 (ovIL-10) over the C terminal two-thirds of the polypeptide, but not in the N terminal third. The immuno-suppressive and immuno-stimulatory activities of orfvIL-10 and ovIL-10 were compared. Both orfvIL-10 and ovIL-10 inhibited TNF-α and IL-8 cytokine production from stimulated ovine macrophages and keratinocytes and IFN-γ and GM-CSF production from peripheral blood lymphocytes. OrfvIL-10 and ovIL-10 co-stimulated both ovine and murine mast cell proliferation in conjunction with IL-3 (ovine) or IL-4 (murine). Isoleucine at position 87 (Ile87) of the mature human IL-10 (huIL-10) has been reported as essential for the immuno-stimulatory activity of huIL-10. In spite of the differences in amino acids within the N-terminal third of orfvIL-10 compared with ovIL-10 and substitution of Ile87 with Ala87 in ovIL-10, these variants of ovIL-10 and orfvIL-10 all co-stimulated mast cell proliferation and inhibited macrophage IL-8 production. As ovIL-10 and orfvIL-10 have a similar structure to huIL-10 and conserved receptor-binding residues, it was concluded that Ile87 is not essential for IL-10 immuno-stimulatory activity. Finally, ovine keratinocytes do not express ovIL-10. This might explain why orf virus has evolved a viral IL-10.