A comparison of the anti-inflammatory and immuno-stimulatory activities of orf virus and ovine interleukin-10.
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-alpha and IL-8 cytokine production from stimulated ovine macrophages and keratinocytes and IFN-gamma 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 (Ile(87)) 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 Ile(87) with Ala(87) 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 Ile(87) 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.
Haig
David M
DM
The Moredun Research Institute, International Research Center, Pentlands Science Park, Bush Loan, EH26 0PZ, Penicuik, UK.haigd@mri.sari.ac.uk
Thomson
Jacqueline
J
McInnes
Colin J
CJ
Deane
David L
DL
Anderson
Ian E
IE
McCaughan
Catherine A
CA
Imlach
Wendy
W
Mercer
Andrew A
AA
Howard
Chris J
CJ
Fleming
Stephen B
SB
D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000276:immunology*; D016753:Interleukin-10 / Q000737:chemistry / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D015603:Keratinocytes / Q000276:immunology / Q000821:virology; D016676:Macrophages, Alveolar / Q000276:immunology / Q000821:virology; D008407:Mast Cells / Q000276:immunology / Q000821:virology; D051379:Mice; D008969:Molecular Sequence Data; D009923:Orf virus / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity; D012756:Sheep / Q000276:immunology*
D016207:Cytokines; D016753:Interleukin-10