A Broad Spectrum Secreted Chemokine Binding Protein Encoded by a Herpesvirus

doi:10.1084/jem.191.3.573

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© The Rockefeller University Press, 0022-1007/2000/2/573/ $5.00
The Journal of Experimental Medicine, Volume 191, Number 3, February 7, 2000 573-578

Brief Definitive Report

A Broad Spectrum Secreted Chemokine Binding Protein Encoded by a Herpesvirus

Christopher M. Parry^a, J. Pedro Simas^a, Vincent P. Smith^a, C. Andrew Stewart^a, Anthony C. Minson^a, Stacey Efstathiou^a, and Antonio Alcami^a
^a From the Division of Virology, Department of Pathology, University of Cambridge, Cambridge CB2 1QP, United Kingdom

Correspondence to: Stacey Efstathiou, Div. of Virology, Dept. of Pathology, University of Cambridge, Tennis Court Rd., Cambridge CB2 1QP, UK. Tel:44-1223-336919 Fax:44-1223-336926 E-mail:se{at}mole.bio.cam.ac.uk.

Chemokines are a family of small proteins that interact withseven-transmembrane domain receptors and modulate the migrationof immune cells into sites of inflammation and infection. Themurine gammaherpesvirus 68 M3 gene encodes a secreted 44-kDprotein with no sequence similarity to known chemokine receptors.We show that M3 binds a broad range of chemokines, includingCC, CXC, C, and CX₃C chemokines, but does not bind human B cell–specificnor mouse neutrophil–specific CXC chemokines. This herpesviruschemokine binding protein (hvCKBP) blocks the interaction ofchemokines with high-affinity cellular receptors and inhibitschemokine-induced elevation of intracellular calcium levels.hvCKBP is the first soluble chemokine receptor identified inherpesviruses; it represents a novel protein structure withthe ability to bind all subfamilies of chemokines in solutionand has potential therapeutic applications.

Key Words: chemokine, cytokine receptor, virus, viral immune evasion, anti-inflammatoryprotein

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