Selective recognition of the membrane-bound CX3C chemokine, fractalkine, by the human cytomegalovirus-encoded broad-spectrum receptor US28

The 7TM receptor, US28, encoded by human cytomegalovirus binds a broad spec trum of endogenous CC chemokines with sub-nanomolar affinity as determined in homologous competition binding assays, We here find that US28 also recog nizes the membrane-associated CX3C chemokine, fractalkine, with sub-nanomol ar affinity (IC50 = 0.42 +/- 0.09 nM). Importantly, although fractalkine co uld compete with high affinity against the binding of CC chemokines, the se creted CC chemokines were only able to compete for binding against radioact ive fractalkine with very low affinity. It is concluded that US28, which is known to enhance cell-cell fusion processes through interaction with an as yet unidentified, human cell-specific factor, has been optimized by cytome galovirus to selectively recognize the membrane-associated fractalkine, It is suggested that US28 expressed on the surface of infected cells and possi bly on the envelope of the virion is involved in transfer of the virus from cell to cell. (C) 1998 Federation of European Biochemical Societies.