HIV-1 gp120 induces an association between CD4 and the chemokine receptor CXCR4.
For efficient entry into target cells, certain T cell-tropic HIV-1 isolates require both CD4 and the coreceptor CXCR4. However, the molecular interactions among CD4, CXCR4, and the HIV-1 envelope glycoproteins are only now being elucidated. Here we show that the binding of soluble gp120 from one macrophage-tropic and four T cell-tropic viruses to a CD4+, but not to a CD4-, T cell line, decreased the binding of an mAb specific for CXCR4 to its epitope, implying an interaction among gp120, CD4, and CXCR4. To confirm such an interaction, we conducted double- and triple-color confocal laser scanning microscopy on CD4+/CXCR4+ cells and determined the extent of CD4 and CXCR4 colocalization by a semiquantitative analysis. In the absence of gp120, a low level of constitutive colocalization between CD4 and CXCR4 was observed. Treatment with T cell-tropic-derived gp120 and, to a lesser extent, macrophage-tropic-derived gp120, increased the colocalization of CD4 with CXCR4, and triple staining indicated that gp120 was associated with the CD4-CXCR4 complexes. Cocapping of the gp120-CD4-CXCR4 complexes at 37 degrees C resulted in the cointernalization of a proportion of the gp120-CXCR4 complexes into intracellular vesicles. These data demonstrate that the binding of gp120 to CD4+ T cells induces the formation of a trimolecular complex consisting of gp120, CD4, and the HIV-1 coreceptor molecule CXCR4.
Ugolini
S
S
Center of Immunology of Marseille-Luminy, France.
Moulard
M
M
Mondor
I
I
Barois
N
N
Demandolx
D
D
Hoxie
J
J
Brelot
A
A
Alizon
M
M
Davoust
J
J
Sattentau
Q J
QJ
D000818:Animals; D015704:CD4 Antigens / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism* / Q000821:virology; D002460:Cell Line; D015699:HIV Envelope Protein gp120 / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D018613:Microscopy, Confocal; D011940:Receptor Aggregation / Q000187:drug effects; D019718:Receptors, CXCR4; D015728:Receptors, HIV / Q000378:metabolism*
D015704:CD4 Antigens; D015699:HIV Envelope Protein gp120; D008565:Membrane Proteins; D019718:Receptors, CXCR4; D015728:Receptors, HIV