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*
Sir William Dunn School of Pathology, University of Oxford, Oxford; and
Imperial College School of Medicine at the National Heart and Lung Institute, London, United Kingdom
Chemokines direct migration of immune cells into sites of inflammation and infection. Chemokine receptors are seven-transmembrane domain proteins that, in contrast to other cytokine receptors, cannot be easily engineered as soluble chemokine inhibitors. Poxviruses encode several soluble cytokine receptors to evade immune surveillance, providing new strategies for immune modulation. Here we show that vaccinia virus and other orthopoxviruses (cowpox and camelpox) express a secreted 35-kDa chemokine binding protein (vCKBP) with no sequence similarity to known cellular chemokine receptors. The vCKBP binds CC, but not CXC or C, chemokines with high affinity (Kd = 0.1–15 nM for different CC chemokines), blocks the interaction of chemokines with cellular receptors, and inhibits chemokine-induced elevation of intracellular calcium levels and cell migration in vitro, thus representing a soluble inhibitor that binds and sequesters chemokines. The potential of vCKBP as a therapeutic agent in vivo was illustrated in a guinea pig skin model by the blockade of eotaxin-induced eosinophil infiltration, a feature of allergic inflammatory reactions. Furthermore, vCKBP may enable the rational design of antagonists to neutralize pathogens that use chemokine receptors to initiate infection, such as HIV or the malarial parasite.
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J. A. Symons, E. Adams, D. C. Tscharke, P. C. Reading, H. Waldmann, and G. L. Smith The vaccinia virus C12L protein inhibits mouse IL-18 and promotes virus virulence in the murine intranasal model J. Gen. Virol., November 1, 2002; 83(11): 2833 - 2844. [Abstract] [Full Text] [PDF]
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J. A. Symons, D. C. Tscharke, N. Price, and G. L. Smith A study of the vaccinia virus interferon-{gamma} receptor and its contribution to virus virulence J. Gen. Virol., August 1, 2002; 83(8): 1953 - 1964. [Abstract] [Full Text] [PDF]
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N. Bartlett, J. A. Symons, D. C. Tscharke, and G. L. Smith The vaccinia virus N1L protein is an intracellular homodimer that promotes virulence J. Gen. Virol., August 1, 2002; 83(8): 1965 - 1976. [Abstract] [Full Text] [PDF]
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D. C. Tscharke, P. C. Reading, and G. L. Smith Dermal infection with vaccinia virus reveals roles for virus proteins not seen using other inoculation routes J. Gen. Virol., August 1, 2002; 83(8): 1977 - 1986. [Abstract] [Full Text] [PDF]
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J. F. Panus, C. A. Smith, C. A. Ray, T. D. Smith, D. D. Patel, and D. J. Pickup Cowpox virus encodes a fifth member of the tumor necrosis factor receptor family: A soluble, secreted CD30 homologue PNAS, June 11, 2002; 99(12): 8348 - 8353. [Abstract] [Full Text] [PDF]
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C. Gubser and G. L. Smith The sequence of camelpox virus shows it is most closely related to variola virus, the cause of smallpox J. Gen. Virol., April 1, 2002; 83(4): 855 - 872. [Abstract] [Full Text] [PDF]
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A. Alcami and G. L. Smith The vaccinia virus soluble interferon-{gamma} receptor is a homodimer J. Gen. Virol., March 1, 2002; 83(3): 545 - 549. [Abstract] [Full Text] [PDF]
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V. P. Smith and A. Alcami Inhibition of Interferons by Ectromelia Virus J. Virol., February 1, 2002; 76(3): 1124 - 1134. [Abstract] [Full Text] [PDF]
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C. Penido, H. C. Castro-Faria-Neto, A. Vieira-de-Abreu, R. T. Figueiredo, A. Pelled, M. A. Martins, P. J. Jose, T. J. Williams, and P. T. Bozza LPS Induces Eosinophil Migration via CCR3 Signaling Through a Mechanism Independent of RANTES and Eotaxin Am. J. Respir. Cell Mol. Biol., December 1, 2001; 25(6): 707 - 716. [Abstract] [Full Text] [PDF]
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C. G. Beck, C. Studer, J.-F. Zuber, B. J. Demange, U. Manning, and R. Urfer The Viral CC Chemokine-binding Protein vCCI Inhibits Monocyte Chemoattractant Protein-1 Activity by Masking Its CCR2B-binding Site J. Biol. Chem., November 9, 2001; 276(46): 43270 - 43276. [Abstract] [Full Text] [PDF]
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 S. W. Chensue Molecular Machinations: Chemokine Signals in Host-Pathogen Interactions Clin. Microbiol. Rev., October 1, 2001; 14(4): 821 - 835. [Abstract] [Full Text] [PDF]
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A. Ng, D. C. Tscharke, P. C. Reading, and G. L. Smith The vaccinia virus A41L protein is a soluble 30 kDa glycoprotein that affects virus virulence J. Gen. Virol., September 1, 2001; 82(9): 2095 - 2105. [Abstract] [Full Text] [PDF]
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A. Bridgeman, P. G. Stevenson, J. P. Simas, and S. Efstathiou A Secreted Chemokine Binding Protein Encoded by Murine Gammaherpesvirus-68 Is Necessary for the Establishment of a Normal Latent Load J. Exp. Med., August 6, 2001; 194(3): 301 - 312. [Abstract] [Full Text] [PDF]
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H. R. Luttichau, J. Gerstoft, and T. W. Schwartz MC148 encoded by human molluscum contagiosum poxvirus is an antagonist for human but not murine CCR8 J. Leukoc. Biol., August 1, 2001; 70(2): 277 - 282. [Abstract] [Full Text] [PDF]
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F. Almazan, D. C. Tscharke, and G. L. Smith The Vaccinia Virus Superoxide Dismutase-Like Protein (A45R) Is a Virion Component That Is Nonessential for Virus Replication J. Virol., August 1, 2001; 75(15): 7018 - 7029. [Abstract] [Full Text]
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B. T. Seet, R. Singh, C. Paavola, E. K. Lau, T. M. Handel, and G. McFadden Molecular determinants for CC-chemokine recognition by a poxvirus CC-chemokine inhibitor PNAS, July 19, 2001; (2001) 171069398. [Abstract] [Full Text] [PDF]
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M. Saraiva and A. Alcami CrmE, a Novel Soluble Tumor Necrosis Factor Receptor Encoded by Poxviruses J. Virol., January 1, 2001; 75(1): 226 - 233. [Abstract] [Full Text]
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F. J. Culley, A. Brown, D. M. Conroy, I. Sabroe, D. I. Pritchard, and T. J. Williams Eotaxin Is Specifically Cleaved by Hookworm Metalloproteases Preventing Its Action In Vitro and In Vivo J. Immunol., December 1, 2000; 165(11): 6447 - 6453. [Abstract] [Full Text] [PDF]
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V. P. Smith and A. Alcami Expression of Secreted Cytokine and Chemokine Inhibitors by Ectromelia Virus J. Virol., September 15, 2000; 74(18): 8460 - 8471. [Abstract] [Full Text]
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V. van Berkel, J. Barrett, H. L. Tiffany, D. H. Fremont, P. M. Murphy, G. McFadden, S. H. Speck, and H. W. Virgin IV Identification of a Gammaherpesvirus Selective Chemokine Binding Protein That Inhibits Chemokine Action J. Virol., August 1, 2000; 74(15): 6741 - 6747. [Abstract] [Full Text]
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V. P. Smith, N. A. Bryant, and A. Alcamí Ectromelia, vaccinia and cowpox viruses encode secreted interleukin-18-binding proteins J. Gen. Virol., May 1, 2000; 81(5): 1223 - 1230. [Abstract] [Full Text]
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C. L. Afonso, E. R. Tulman, Z. Lu, L. Zsak, G. F. Kutish, and D. L. Rock The Genome of Fowlpox Virus J. Virol., April 15, 2000; 74(8): 3815 - 3831. [Abstract] [Full Text]
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 P. M. Murphy, M. Baggiolini, I. F. Charo, C. A. Hebert, R. Horuk, K. Matsushima, L. H. Miller, J. J. Oppenheim, and C. A. Power International Union of Pharmacology. XXII. Nomenclature for Chemokine Receptors Pharmacol. Rev., March 1, 2000; 52(1): 145 - 176. [Abstract] [Full Text] [PDF]
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C. M. Parry, J. P. Simas, V. P. Smith, C. A. Stewart, A. C. Minson, S. Efstathiou, and A. Alcami A Broad Spectrum Secreted Chemokine Binding Protein Encoded by a Herpesvirus J. Exp. Med., February 7, 2000; 191(3): 573 - 578. [Abstract] [Full Text] [PDF]
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 J. G. Cyster Chemokines and Cell Migration in Secondary Lymphoid Organs Science, December 10, 1999; 286(5447): 2098 - 2102. [Abstract] [Full Text]
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G. Camarda, G. Spinetti, G. Bernardini, C. Mair, N. Davis-Poynter, M. C. Capogrossi, and M. Napolitano The Equine Herpesvirus 2 E1 Open Reading Frame Encodes a Functional Chemokine Receptor J. Virol., December 1, 1999; 73(12): 9843 - 9848. [Abstract] [Full Text]
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A. Carfi, C. A. Smith, P. J. Smolak, J. McGrew, and D. C. Wiley Structure of a soluble secreted chemokine inhibitor vCCI (p35) from cowpox virus PNAS, October 26, 1999; 96(22): 12379 - 12383. [Abstract] [Full Text] [PDF]
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