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      The CXC chemokine SDF-1 is the ligand for LESTR/fusin and prevents infection by T-cell-line-adapted HIV-1.


      Animals, Anti-HIV Agents, metabolism, pharmacology, Antigens, CD4, genetics, Binding, Competitive, CHO Cells, Calcium, Chemokine CCL4, Chemokine CCL5, Chemokine CXCL12, Chemokines, Chemokines, CXC, Cricetinae, Cricetulus, DNA, Viral, HIV-1, drug effects, HeLa Cells, Humans, Leukocytes, Mononuclear, virology, Ligands, Macrophage Inflammatory Proteins, Macrophages, Membrane Fusion, Membrane Proteins, Molecular Sequence Data, Proviruses, Receptors, CXCR4, Receptors, HIV, Transfection

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          A putative chemokine receptor that we previously cloned and termed LESTR has recently been shown to function as a co-receptor (termed fusin) for lymphocyte-tropic HIV-1 strains. Cells expressing CD4 became permissive to infection with T-cell-line-adapted HIV-1 strains of the syncytium-inducing phenotype after transfection with LESTR/fusin complementary DNA. We report here the indentification of a human chemokine of the CXC type, stromal cell-derived factor 1 (SDF-1), as the natural ligand for LESTR/fusin, and we propose the term CXCR-4 for this receptor, in keeping with the new chemokine-receptor nomenclature. SDF-1 activates Chinese hamster ovary (CHO) cells transfected with CXCR-4 cDNA as well as blood leukocytes and lymphocytes. In cell lines expressing CXCR-4 and CD4, and in blood lymphocytes, SDF-1 is a powerful inhibitor of infection by lymphocyte-tropic HIV-1 strains, whereas the CC chemokines RANTES, MIP-1 alpha and MIP-1 beta, which were shown previously to prevent infection with primary, monocyte-tropic viruses, 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 viruses which are characteristic of the late stages of AIDS.

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