THE CXC CHEMOKINE SDF-1 IS THE LIGAND FOR LESTR FUSIN AND PREVENTS INFECTION BY T-CELL-LINE-ADAPTED HIV-1/

A PUTATIVE chemokine receptor that we previously cloned and termed LES TR(1) has recently been shown to function as a co-receptor (termed fus in) for lymphocyte-tropic HIV-1 strains(2), Cells expressing CD4 becam e permissive to infection with T-cell-line-adapted HIV-1 strains of th e syncytium-inducing phenotype after transfection with LESTR/fusin com plementary DNA, We report here the identification of a human chemokine of the CXC type, stromal cell-derived factor 1 (SDF-1), as the natura l ligand for LESTR/fusin, and we propose the term CXCR-4 for this rece ptor, in keeping with the new chemokine-receptor nomenclature, SDF-1 a ctivates Chinese hamster ovary (CHO) cells transfected with CXCR-4 cDN A as well as blood leukocytes and lymphocytes. In cell lines expressin g CXCR-4 and CD4, and in blood lymphocytes, SDF-1 is a powerful inhibi tor of infection by lymphocyte-tropic HIV-1 strains, whereas the CC ch emokines RANTES, MIP-1 alpha and MIP-1 beta, which were shown previous ly to prevent infection with primary, monocyte-tropic viruses(3), are inactive, In combination with CC chemokines, which block the infection with monocyte/macrophage-tropic viruses, SDF-1 could help to decrease virus load and prevent the emergence of the syncytium-inducing viruse s which are characteristic of the late stages of AIDS(4).