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 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.
Oberlin
E
E
Unité d'Immunologie Virale, Institut Pasteur, Paris, France.
Amara
A
A
Bachelerie
F
F
Bessia
C
C
Virelizier
J L
JL
Arenzana-Seisdedos
F
F
Schwartz
O
O
Heard
J M
JM
Clark-Lewis
I
I
Legler
D F
DF
Loetscher
M
M
Baggiolini
M
M
Moser
B
B
D000818:Animals; D019380:Anti-HIV Agents / Q000378:metabolism / Q000494:pharmacology*; D001667:Binding, Competitive; D015704:CD4 Antigens / Q000235:genetics / Q000378:metabolism; D016466:CHO Cells; D002118:Calcium / Q000378:metabolism; D054407:Chemokine CCL4; D018946:Chemokine CCL5 / Q000378:metabolism; D054377:Chemokine CXCL12; D018925:Chemokines / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology*; D019743:Chemokines, CXC; D006224:Cricetinae; D003412:Cricetulus; D004279:DNA, Viral / Q000378:metabolism; D015497:HIV-1 / Q000187:drug effects* / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000821:virology; D008024:Ligands; D019402:Macrophage Inflammatory Proteins / Q000378:metabolism; D008264:Macrophages / Q000821:virology; D008561:Membrane Fusion; D008565:Membrane Proteins / Q000378:metabolism*; D008969:Molecular Sequence Data; D011533:Proviruses / Q000235:genetics; D019718:Receptors, CXCR4; D015728:Receptors, HIV / Q000378:metabolism*; D014162:Transfection
D019380:Anti-HIV Agents; D015704:CD4 Antigens; C515255:CXCL12 protein, human; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D054377:Chemokine CXCL12; D018925:Chemokines; D019743:Chemokines, CXC; D004279:DNA, Viral; D008024:Ligands; D019402:Macrophage Inflammatory Proteins; D008565:Membrane Proteins; D019718:Receptors, CXCR4; D015728:Receptors, HIV; D002118:Calcium