The
MC148 CC chemokine from the human poxvirus
molluscum contagiosum (MCV) was probed in parallel with viral
macrophage inflammatory protein (
vMIP)-II encoded by human herpesvirus 8 (HHV8) in 16 classified human
chemokine receptors. In competition binding using radiolabeled endogenous
chemokines as well as radiolabeled MC148, MC148 bound with high affinity only to CCR8. In
calcium mobilization assays, MC148 had no effect on its own on any of the
chemokine receptors, but in a dose-dependent manner blocked the stimulatory effect of the endogenous I-309
chemokine on CCR8 without affecting
chemokine-induced signaling of any other receptor. In contrast,
vMIP-II acted as an antagonist on 10 of the 16
chemokine receptors, covering all four classes: XCR, CCR, CXCR, and CX(3)CR. In chemotaxis assays, MC148 specifically blocked the I-309-induced response but, for example, not
stromal cell-derived factor 1alpha,
monocyte chemoattractant protein 1, or
interleukin 8-induced chemotaxis. We thus concluded that the two viruses choose two different ways to block the
chemokine system: HHV8 encodes the broad-spectrum
chemokine antagonist
vMIP-II, whereas MCV encodes a highly selective CCR8 antagonist, MC148, conceivably to interfere with monocyte invasion and dendritic cell function. Because of its pharmacological selectivity, the MC148
protein could be a useful tool in the delineation of the role played by CCR8 and its endogenous
ligand, I-309.