The herpesvirus 8-encoded chemokine vMIP-II, but not the poxvirus-encoded chemokine MC148, inhibits the CCR10 receptor.
The viral chemokine antagonist vMIP-II encoded by human herpesvirus 8 (HHV8) and MC148 encoded by the poxvirus - Molluscum contagiosum - were tested against the newly identified chemokine receptor CCR10. As the CCR10 ligand ESkine / CCL27 had the highest identity to MC148 and because both chemokines are expressed in the skin we suspected MC148 to block CCR10. However, in calcium mobilization assays we found MC148 unable to block CCR10 in micromolar concentrations in contrast to vMIP-II. (125)I-MC148 was only able to bind to CCR8, but not to CCR10, CCR11, CXCR6 / BONZO, APJ, DARC or the orphan receptors BOB, EBI-II, GPR4, GPR17, HCR or RDC1. We conclude that MC148 is a highly selective CCR8 antagonist conceivably optimized to interfere with NK cell and monocyte invasion, whereas the broad-spectrum antagonist vMIP-II protects HHV8 by blocking multiple receptors.
Lüttichau
H R
HR
Laboratory for Molecular Pharmacology, Department of Pharmacology, Panum Institute, Copenhagen, Denmark. hrl@molpharm.dk
Lewis
I C
IC
Gerstoft
J
J
Schwartz
T W
TW
D000818:Animals; D001665:Binding Sites; D019556:COS Cells; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects; D002460:Cell Line; D018925:Chemokines / Q000494:pharmacology*; D019288:Herpesvirus 8, Human; D008024:Ligands; D051379:Mice; D008977:Molluscum contagiosum virus; D054447:Receptors, CCR10; D054397:Receptors, CCR3; D019707:Receptors, Chemokine / Q000819:agonists / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D013379:Substrate Specificity; D014162:Transfection
C515706:CCR10 protein, human; C515350:CCR3 protein, human; C515707:Ccr10 protein, mouse; C515351:Ccr3 protein, mouse; D018925:Chemokines; D008024:Ligands; D054447:Receptors, CCR10; D054397:Receptors, CCR3; D019707:Receptors, Chemokine; C108059:vMIP-II; D002118:Calcium