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Journal of Virology, February 2000, p. 1313-1320, Vol. 74, No. 3
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Orf Virus Encodes a Novel Secreted Protein Inhibitor of Granulocyte-Macrophage Colony-Stimulating Factor and Interleukin-2

David Deane,1 Colin J. McInnes,1,* Ann Percival,1 Ann Wood,1 Jackie Thomson,1 Andrea Lear,dagger Janice Gilray,1 Stephen Fleming,2 Andrew Mercer,2 and David Haig1

Moredun Research Institute, International Research Centre, Penicuik, Scotland,1 and HRC Virus Research Unit, University of Otago, Dunedin, New Zealand2

Received 2 August 1999/Accepted 4 November 1999

The parapoxvirus orf virus encodes a novel soluble protein inhibitor of ovine granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-2 (IL-2). The GM-CSF- and IL-2-inhibitory factor (GIF) gene was expressed as an intermediate-late viral gene in orf virus-infected cells. GIF formed homodimers and tetramers in solution, and it bound ovine GM-CSF with a Kd of 369 pM and ovine IL-2 with a Kd of 1.04 nM. GIF did not bind human GM-CSF or IL-2 in spite of the fact that orf virus is a human pathogen. GIF was detected in afferent lymph plasma draining the skin site of orf virus reinfection and was associated with reduced levels of lymph GM-CSF. GIF expression by orf virus indicates that GM-CSF and IL-2 are important in host antiviral immunity.

* Corresponding author. Mailing address: Moredun Research Institute, International Research Centre, Pentlands Science Park, Bush Loan, Penicuik EH26 0PZ, Scotland, United Kingdom. Phone: 44 (0)131 445 5111. Fax: 44 (0)131 445 6111. E-mail: mcinc{at}mri.sari.ac.uk.

dagger Present address: Astra Clinical Research Unit, Edinburgh, Scotland.

Journal of Virology, February 2000, p. 1313-1320, Vol. 74, No. 3
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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