Orf virus encodes a novel secreted protein inhibitor of granulocyte-macrophage colony-stimulating factor and interleukin-2

The parapoxvirus orf virus encodes a novel soluble protein inhibitor of ovi ne granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleuki n-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 wa s detected in afferent lymph plasma draining the skin site of orf virus rei nfection and was associated with reduced levels of lymph GM-CSF. GIF expres sion by orf virus indicates that GM-CSF and IL-2 are important in host anti viral immunity.