Detalle de: The gammaherpesvirus chemokine binding protein can inhibit the interaction of chemokines with glycosaminoglycans

Chemokines are small glycosaminoglycan (GAG) binding proteins that direct the migration of leukocytes by signaling through G protein coupled receptors (GPCR). Many viruses encode proteins that disrupt chemokine responses. The murine gammaherpesvirus‐68 gene M3 encodes a chemokine binding protein (vCKBP‐3), which has no sequence similarity to chemokine receptors. Initial characterization of vCKBP‐3 showed that it inhibits receptor binding and chemokine‐induced calcium influx. The structural requirements for the chemokines CXCL8 and CCL2 to bind to vCKBP‐3 have been determined. Both chemokines bind to vCKBP‐3 via their N‐loop, a site that can participate in GAG binding for some chemokines. We have investigated the effect of vCKBP‐3 on the interaction of chemokines with GAGs. We found that vCKBP‐3 can prevent a range of chemokines from binding to GAGs. Moreover, we also found that vCKBP‐3 can displace chemokines from a heparin‐coated surface. Together, these data imply that vCKBP‐3 can inhibit chemokine activity at two distinct levels. First, it inhibits chemokines from binding to their GPCR. Second, it inhibits their GAG binding and disrupts pre‐formed chemokine gradients. This dual ability of vCKBP‐3 makes it a more effective inhibitor of chemokine activity.