DOI: 10.4049/jimmunol.160.2.624. Blockade of Chemokine Activity by a Soluble Chemokine Binding Protein from Vaccinia Virus

Blockade of Chemokine Activity by a Soluble Chemokine Binding Protein from Vaccinia Virus

10.4049/jimmunol.160.2.624

Crossref journal-article

Oxford University Press (OUP)

The Journal of Immunology (286)

Abstract

Abstract 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.

Bibliography

AlcamiÌ, A., Symons, J. A., Collins, P. D., Williams, T. J., & Smith, G. L. (1998). Blockade of Chemokine Activity by a Soluble Chemokine Binding Protein from Vaccinia Virus. The Journal of Immunology, 160(2), 624â633.

Authors 5

Antonio Alcamí (first)
Julian A Symons (additional)
Paul D Collins (additional)
Timothy J Williams (additional)
Geoffrey L Smith (additional)

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Dates

Type	When
Created	2 years, 7 months ago (Jan. 1, 2023, 12:01 p.m.)
Deposited	4 months, 4 weeks ago (March 30, 2025, 10:23 p.m.)
Indexed	1 month, 3 weeks ago (July 7, 2025, 1:26 a.m.)
Issued	27 years, 7 months ago (Jan. 1, 1998)
Published	27 years, 7 months ago (Jan. 1, 1998)
Published Online	27 years, 7 months ago (Jan. 15, 1998)
Published Print	27 years, 7 months ago (Jan. 15, 1998)

Funders 0

None

BibTeX

@article{Alcami__1998, title={Blockade of Chemokine Activity by a Soluble Chemokine Binding Protein from Vaccinia Virus}, volume={160}, ISSN={1550-6606}, url={http://dx.doi.org/10.4049/jimmunol.160.2.624}, DOI={10.4049/jimmunol.160.2.624}, number={2}, journal={The Journal of Immunology}, publisher={Oxford University Press (OUP)}, author={Alcamí, Antonio and Symons, Julian A and Collins, Paul D and Williams, Timothy J and Smith, Geoffrey L}, year={1998}, month=jan, pages={624–633} }

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