IDENTIFICATION OF CX(3)CR1 - A CHEMOTACTIC RECEPTOR FOR THE HUMAN CX3C CHEMOKINE FRACTALKINE AND A FUSION CORECEPTOR FOR HIV-1

Fractalkine is a multimodular human leukocyte chemoattractant protein and a member of the chemokine superfamily. Unlike other human chemokin es, the chemokine domain of fractalkine has three amino acids between two conserved cysteines, referred to as the CX3C motif. Both plasma me mbrane-associated and shed forms of fractalkine have been identified. Here, we show that the recombinant 76-amino acid chemokine domain of f ractalkine is a potent and highly specific chemotactic agonist at a hu man orphan receptor previously named V28 or alternatively CMKBRL1 (che mokine beta receptor-like 1), which was shown previously to be express ed in neutrophils, monocytes, T lymphocytes, and several solid organs, including brain. CMKBRL1/V28 also functioned with CD4 as a coreceptor for the envelope protein from a primary isolate of HIV-1 in a cell-ce ll fusion assay, and fusion was potently and specifically inhibited by fractalkine. Thus CMKBRL1/V28 is a specific receptor for fractalkine, and we propose to rename it CX(3)CR1 (CX3C chemokine receptor 1), acc ording to an accepted nomenclature system.