A broad spectrum secreted chemokine binding protein encoded by a herpesvirus.
Chemokines are a family of small proteins that interact with seven-transmembrane domain receptors and modulate the migration of immune cells into sites of inflammation and infection. The murine gammaherpesvirus 68 M3 gene encodes a secreted 44-kD protein with no sequence similarity to known chemokine receptors. We show that M3 binds a broad range of chemokines, including CC, CXC, C, and CX(3)C chemokines, but does not bind human B cell-specific nor mouse neutrophil-specific CXC chemokines. This herpesvirus chemokine binding protein (hvCKBP) blocks the interaction of chemokines with high-affinity cellular receptors and inhibits chemokine-induced elevation of intracellular calcium levels. hvCKBP is the first soluble chemokine receptor identified in herpesviruses; it represents a novel protein structure with the ability to bind all subfamilies of chemokines in solution and has potential therapeutic applications.
Parry
C M
CM
Division of Virology, Department of Pathology, University of Cambridge, Cambridge CB2 1QP, United Kingdom.
Simas
J P
JP
Smith
V P
VP
Stewart
C A
CA
Minson
A C
AC
Efstathiou
S
S
Alcami
A
A
D000818:Animals; D001667:Binding, Competitive; D002460:Cell Line; D054407:Chemokine CCL4; D018925:Chemokines / Q000494:pharmacology; D006224:Cricetinae; D018142:Gammaherpesvirinae / Q000235:genetics*; D006493:Heparin; D006497:Heparan Sulfate; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism; D007457:Iodine Radioisotopes; D019402:Macrophage Inflammatory Proteins / Q000378:metabolism; D051379:Mice; D016366:Open Reading Frames; D011485:Protein Binding / Q000187:drug effects; D019707:Receptors, Chemokine / Q000235:genetics* / Q000378:metabolism; D014764:Viral Proteins / Q000235:genetics* / Q000378:metabolism
D054407:Chemokine CCL4; D018925:Chemokines; D006493:Heparin; D006497:Heparan Sulfate; D016209:Interleukin-8; D007457:Iodine Radioisotopes; D019402:Macrophage Inflammatory Proteins; D019707:Receptors, Chemokine; D014764:Viral Proteins; C118862:M3 protein, Murine gammaherpesvirus