HIV-1 gp120 induces an association between CD4 and the chemokine receptor CXCR4
Ugolini, S.; Moulard, M.; Mondor, I.; Barois, N.; Demandolx, D.; Hoxie, J.; Brelot, A.; Alizon, M.; Davoust, J.; Sattentau, Q.J.
Journal of Immunology 159(6): 3000-3008
1997
ISSN/ISBN: 0022-1767 PMID: 9300725 Document Number: 482273
This study shows 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 a monoclonal antibody specific for CXCR4 to its epitope, implying an interaction among gp120, CD4, and CXCR4. To confirm such an interaction, double- and triple-colour confocal laser scanning microscopy was performed on CD4+/CXCR4+ cells and the extent of CD4 and CXCR4 colocalization was determined 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.