Orf virus-encoded chemokine-binding protein is a potent inhibitor of inflammatory monocyte recruitment in a mouse skin model.
The parapoxvirus orf virus causes pustular dermatitis in sheep and is transmissible to humans. The virus encodes a secreted chemokine-binding protein (CBP). We examined the ability of this protein to inhibit migration of murine monocytes in response to CC inflammatory chemokines, using chemotaxis assays, and its effects on monocyte recruitment into the skin, using a mouse model in which inflammation was induced with bacterial lipopolysaccharide. CBP was shown to bind murine chemokines CCL2, CCL3 and CCL5 with high affinity by surface plasmon resonance and it completely inhibited chemokine-induced migration of monocytes at a CBP:chemokine molar ratio of 4:1. In the mouse, low levels of CBP potently inhibited the recruitment of Gr-1+/CD11b+ monocytes to the site of inflammation in the skin but had little effect on neutrophil recruitment, suggesting that this factor plays a role in disrupting chemokine-induced recruitment of specific immune cell types to infection sites.
Lateef
Zabeen
Z
Department of Microbiology and Immunology, University of Otago, PO Box 56, Dunedin, New Zealand.
Baird
Margaret A
MA
Department of Microbiology and Immunology, University of Otago, PO Box 56, Dunedin, New Zealand.
Wise
Lyn M
LM
Department of Microbiology and Immunology, University of Otago, PO Box 56, Dunedin, New Zealand.
Mercer
Andrew A
AA
Department of Microbiology and Immunology, University of Otago, PO Box 56, Dunedin, New Zealand.
Fleming
Stephen B
SB
Department of Microbiology and Immunology, University of Otago, PO Box 56, Dunedin, New Zealand.
D000818:Animals; D002465:Cell Movement / Q000276:immunology; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000378:metabolism; D054405:Chemokine CCL3 / Q000378:metabolism; D018946:Chemokine CCL5 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000276:immunology*; D009923:Orf virus / Q000276:immunology / Q000472:pathogenicity* / Q000502:physiology; D011485:Protein Binding; D017193:Skin Diseases, Viral / Q000473:pathology / Q000821:virology*; D014764:Viral Proteins / Q000502:physiology*; D037521:Virulence Factors / Q000502:physiology*
C491768:Ccl2 protein, mouse; C496534:Ccl3 protein, mouse; C503460:Ccl5 protein, mouse; D018932:Chemokine CCL2; D054405:Chemokine CCL3; D018946:Chemokine CCL5; D014764:Viral Proteins; D037521:Virulence Factors