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Animal: DNA Viruses |
Virus Research Unit and Centre for Gene Research, Department of Microbiology, University of Otago, PO Box 56, Dunedin, New Zealand1
The Moredun Research Institute, International Research Centre, Pentland Science Park, Penicuik EH26 OPZ, UK2
Author for correspondence: Stephen Fleming. Fax +64 3 4797744. e-mail stephen.fleming{at}stonebow.otago.ac.nz
Orf virus (ORFV) is the type species of the parapoxvirus genus and produces cutaneous pustular lesions in sheep, goats and humans. The genome encodes a polypeptide with remarkable homology to interleukin-10 (IL-10), particularly ovine IL-10, and also to IL-10-like proteins encoded by Epstein–Barr virus (EBV) and equine herpesvirus. IL-10 is a pleiotropic cytokine that can exert either immunostimulatory or immunosuppressive effects on many cell types. We have expressed and purified C-terminal FLAG and His6-tagged versions of ORFV-IL-10 and shown that ORFV-IL-10 costimulates murine mast cells (MC/9) and inhibits tumour necrosis factor-
synthesis in activated mouse peritoneal macrophages. Our results demonstrate that although ORFV-IL-10 is structurally similar to EBV-IL-10 it has evolved a different spectrum of activities. EBV-IL-10 does not stimulate the proliferation of thymocytes or mast cells whereas ORFV-IL-10 has both of these activities. Recent studies show that the critical difference in molecular structure of human IL-10 and EBV-IL-10, which may be the basis of their functional differences, is linked to a single amino acid substitution. Consistent with the activity spectrum reported here for ORFV-IL-10, the viral gene encodes the critical amino acid seen in human IL-10. Although the ORFV-IL-10 gene has clearly undergone significant evolutionary change at the nucleotide level compared with ovine IL-10, it has largely retained the polypeptide structure and functional characteristics of its ovine counterpart, suggesting that mutations of the gene to a potentially more potent immunosuppressive form may compromise the co-existence of host and virus.
This article has been cited by other articles:
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  S. B. Fleming, I. E. Anderson, J. Thomson, D. L. Deane, C. J. McInnes, C. A. McCaughan, A. A. Mercer, and D. M. Haig Infection with recombinant orf viruses demonstrates that the viral interleukin-10 is a virulence factor J. Gen. Virol., July 1, 2007; 88(7): 1922 - 1927. [Abstract] [Full Text] [PDF]
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L. Wise, C. McCaughan, C. K. Tan, A. A. Mercer, and S. B. Fleming Orf virus interleukin-10 inhibits cytokine synthesis in activated human THP-1 monocytes, but only partially impairs their proliferation J. Gen. Virol., June 1, 2007; 88(6): 1677 - 1682. [Abstract] [Full Text] [PDF]
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M. K. Inder, N. Ueda, A. A. Mercer, S. B. Fleming, and L. M. Wise Bovine papular stomatitis virus encodes a functionally distinct VEGF that binds both VEGFR-1 and VEGFR-2 J. Gen. Virol., March 1, 2007; 88(3): 781 - 791. [Abstract] [Full Text] [PDF]
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A. Chan, M. Baird, A. A. Mercer, and S. B. Fleming Maturation and function of human dendritic cells are inhibited by orf virus-encoded interleukin-10. J. Gen. Virol., November 1, 2006; 87(Pt 11): 3177 - 3181. [Abstract] [Full Text] [PDF]
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 E. R. Tulman, C. L. Afonso, Z. Lu, L. Zsak, G. F. Kutish, and D. L. Rock The Genome of Canarypox Virus J. Virol., January 1, 2004; 78(1): 353 - 366. [Abstract] [Full Text] [PDF]
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A. R. Wood and C. J. McInnes Transcript mapping of the 'early' genes of Orf virus J. Gen. Virol., November 1, 2003; 84(11): 2993 - 2998. [Abstract] [Full Text] [PDF]
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J. B. Johnston and G. McFadden Poxvirus Immunomodulatory Strategies: Current Perspectives J. Virol., June 1, 2003; 77(11): 6093 - 6100. [Full Text] [PDF]
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Z. Lateef, S. Fleming, G. Halliday, L. Faulkner, A. Mercer, and M. Baird Orf virus-encoded interleukin-10 inhibits maturation, antigen presentation and migration of murine dendritic cells J. Gen. Virol., May 1, 2003; 84(5): 1101 - 1109. [Abstract] [Full Text] [PDF]
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H.-J. Rziha, B. Bauer, K.-H. Adam, M. Rottgen, R. Cottone, M. Henkel, C. Dehio, and M. Buttner Relatedness and heterogeneity at the near-terminal end of the genome of a parapoxvirus bovis 1 strain (B177) compared with parapoxvirus ovis (Orf virus) J. Gen. Virol., May 1, 2003; 84(5): 1111 - 1116. [Abstract] [Full Text] [PDF]
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