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 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.
Deane
D
D
Moredun Research Institute, International Research Centre, Penicuik, Scotland.
McInnes
C J
CJ
Percival
A
A
Wood
A
A
Thomson
J
J
Lear
A
A
Gilray
J
J
Fleming
S
S
Mercer
A
A
Haig
D
D
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D016466:CHO Cells; D002417:Cattle; D002478:Cells, Cultured; D002850:Chromatography, Gel; D006224:Cricetinae; D018076:DNA, Complementary / Q000235:genetics; D019281:Dimerization; D004474:Ecthyma, Contagious / Q000821:virology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D007376:Interleukin-2 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015603:Keratinocytes / Q000821:virology; D008196:Lymph / Q000737:chemistry; D008969:Molecular Sequence Data; D009923:Orf virus / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D012756:Sheep; D014764:Viral Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology
D018076:DNA, Complementary; C403419:GIF protein, orf virus; D007376:Interleukin-2; D011994:Recombinant Proteins; D014764:Viral Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor