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

Author:

Deane David1,McInnes Colin J.1,Percival Ann1,Wood Ann1,Thomson Jackie1,Lear Andrea,Gilray Janice1,Fleming Stephen2,Mercer Andrew2,Haig David1

Affiliation:

1. Moredun Research Institute, International Research Centre, Penicuik, Scotland,1 and

2. HRC Virus Research Unit, University of Otago, Dunedin, New Zealand2

Abstract

ABSTRACT 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 K d of 369 pM and ovine IL-2 with a K d 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.

Publisher

American Society for Microbiology

Subject

Virology,Insect Science,Immunology,Microbiology

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