RECOMBINANT HUMAN CXC-CHEMOKINE RECEPTOR-4 IN MELANOPHORES ARE LINKEDTO G(I) PROTEIN - 7 TRANSMEMBRANE CORECEPTORS FOR HUMAN-IMMUNODEFICIENCY-VIRUS ENTRY INTO CELLS

This article describes the transient expression of the CXC chemokine r eceptor-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 c onsistent with the activation of G(i) protein, This stimulus pathway i s further implicated by the abolition of this response after pretreatm ent of the cells with pertussis toxin, a known method for the inactiva tion of G(i) protein. The fact that SDF-1 alpha does not produce respo nses in nontransfected cells and that treatment of the cells with 12G5 , an antibody specific for the CXC chemokine receptor-4, eliminates th is response indicates that this ligand produces responses by activatio n of this receptor in these cells. The possible relevance to human imm unodeficiency virus (HIV) entry into cells was explored by observing t he effects of SDF-1 alpha on HIV-mediated cell fusion. It was found th at SDF-1 alpha blocked cell-to-cell fusion (as has been previously rep orted) at concentrations 1200-fold greater than those required to prod uce Gi protein mediated responses. The implications of the functional assay to screening for new drugs to block HIV-mediated fusion is discu ssed.