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A chemokine receptor is a cell-surface receptor that recognizes a chemokine. Conventional chemokine receptors couple ligand recognition to G protein signaling, often helping leukocytes respond to spatial chemical cues. A chemokine receptor should not be confused with the secreted chemokine that binds it. The wider family includes atypical members whose signaling and ligand-handling properties require separate description.^[ref]

An important experimental example is a receptor being used for a purpose beyond its normal signaling role. H. Deng and colleagues reported that the receptor then called CC-CKR-5, now CCR5, provided a principal entry cofactor for the envelope proteins of primary macrophage-tropic HIV-1 strains. CD4 alone did not account for the entry requirements, and the result differed from the cofactor used by the tested T-cell-line-adapted viruses.^[ref]

This illustrates why binding, signaling and viral entry must be distinguished. A cell might express CD4 yet lack a compatible additional entry factor; conversely, detecting a chemokine receptor does not demonstrate infection. A receptor-expression comparison can therefore test an entry requirement without establishing that every virus strain uses the same receptor. In migration experiments, receptor expression likewise does not by itself measure the direction, speed or persistence of cell movement.

A co-receptor is a receptor that acts with another receptor in a specified recognition, signaling or entry process. The word describes a functional partnership: which partner is needed depends on the biological system and the measured response. It does not mean that every receptor involved must have the same normal ligand or physiological role.

A revealing example is entry by certain HIV-1 isolates. H. Deng and colleagues reported in 1996 that CD4 alone did not explain entry requirements. The chemokine receptor then called CC-CKR-5, now CCR5, supported entry mediated by the envelopes of tested primary macrophage-tropic HIV-1 strains. The comparison with T-cell-line-adapted viruses showed why a co-receptor must be identified in a particular virus–cell context.^[ref]

The conceptual experiment separates recognition from sufficiency: possessing one required cell-surface receptor does not ensure that a cell has all the components needed for entry. Nor does identifying entry cofactors by itself establish every later step of a productive infection.