The Journal of Experimental Medicine
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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. Parrya, J. Pedro Simasa, Vincent P. Smitha, C. Andrew Stewarta, Anthony C. Minsona, Stacey Efstathioua, and Antonio Alcamia

a From the Division of Virology, Department of Pathology, University of Cambridge, Cambridge CB2 1QP, United Kingdom
Div. of Virology, Dept. of Pathology, University of Cambridge, Tennis Court Rd., Cambridge CB2 1QP, UK.44-1223-33692644-1223-336919

se{at}mole.bio.cam.ac.uk

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 CX3C 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.

Key Words: chemokine • cytokine receptor • virus • viral immune evasion • anti-inflammatory protein

J.P. Simas' present address is Gulbenkian Institute for Science, Rua da Quinta Grande 6, 2780-156 Oeiras, Portugal.

Antonio Alcami, Div. of Virology, Dept. of Pathology, University of Cambridge, Tennis Court Rd., Cambridge CB2 1QP, UK. Phone: 44-1223-336922; Fax: 44-1223-336926; E-mail: aa258@mole.bio.cam.ac.uk

© 2000 The Rockefeller University Press


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