The viral CC chemokine-binding protein vCCI inhibits monocyte chemoattractant protein-1 activity by masking its CCR2B-binding site

Monocyte chemoattractant protein-1 (MCP-1) is a chemotactic cytokine mainly acting on monocytes and T cells that elicits its biological effects by int eracting with the seven-transmembrane helix receptor CCR2B. The vaccinia vi rus strain Lister and many other poxviruses express soluble proteins (vCCI) that bind MCP-1 and other CC chemokines and inhibit their function. In ord er to define the interaction site of MCP-1 with vCCI from vaccinia, surface exposed residues of MCP-1 were identified and mutated to alanine. The MCP- 1 variants were expressed, purified, and their interaction with vCCI was ch aracterized. The site on MCP-1 for vCCI binding is dominated by arginine 18 with important additional contributions from tyrosine 13 and arginine 24. These residues define a binding site that largely overlaps with the CCR2B r eceptor interaction site. The viral chemokine-binding protein vCCI thus inh ibits the biological function of MCP-1 by directly masking its CCR2B recept or-binding site.