Recombinant human CXC-chemokine receptor-4 in melanophores are linked to Gi protein:: Seven transmembrane coreceptors for human immunodeficiency virus entry into cells

This article describes the transient expression of the CXC chemokine receptor-4 in Xenopus laevis melanophores and the resulting functional assay for the endogenous ligand for this receptor stromal cell-derived factor (SDF)-1 alpha. Specifically, it will be shown that SDF-1 alpha produces increased light transmittance in transfected cells that is consistent with the activation of G(i) protein, This stimulus pathway is further implicated by the abolition of this response after pretreatment of the cells with pertussis toxin, a known method for the inactivation of G(i) protein. The fact that SDF-1 alpha does not produce responses in nontransfected cells and that treatment of the cells with 12G5, an antibody specific for the CXC chemokine receptor-4, eliminates this response indicates that this ligand produces responses by activation of this receptor in these cells. The possible relevance to human immunodeficiency virus (HIV) entry into cells was explored by observing the effects of SDF-1 alpha on HIV-mediated cell fusion. It was found that SDF-1 alpha blocked cell-to-cell fusion (as has been previously reported) at concentrations 1200-fold greater than those required to produce Gi protein mediated responses. The implications of the functional assay to screening for new drugs to block HIV-mediated fusion is discussed.