HIV-1 envelope is a neutral antagonist to CXCR4 in T-cells.
The chemokine receptor CXCR4 is the principal coreceptor for X4 strains of HIV-1. We show that gp120 is unable to induce interactions between CXCR4 and G-protein in T-cells, but antagonized the agonist effect of SDF-1alpha, the natural ligand for CXCR4. Gp120 had ten times lower affinity for CXCR4 than CD4, implying that a substantial role for cellular CD4 may be to facilitate binding of the viral envelope to CXCR4. Binding of gp120 to CXCR4 was neither regulated by guanine nucleotides, nor affected by divalent cations, was temperature independent and bound to a homogenous population of CXCR4, which is characteristic for an antagonist to a G-protein coupled receptor. In contrast, SDF-1alpha binds to two affinity states of CXCR4 in T-cell membranes, which are modulated by guanine nucleotides. Binding of SDF-1alpha to CXCR4 was highly temperature dependent. Thus, the interaction of CXCR4 with HIV-1 viral envelope and chemokine exhibits fundamental differences.
Staudinger
R
R
Department of Medicine, New York University School of Medicine, New York, New York, USA.
Wang
X
X
Bandrés
J C
JC
D002412:Cations; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D054377:Chemokine CXCL12; D018925:Chemokines / Q000378:metabolism; D019743:Chemokines, CXC / Q000378:metabolism; D006147:Guanine / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000378:metabolism; D015699:HIV Envelope Protein gp120 / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D008024:Ligands; D011485:Protein Binding; D019718:Receptors, CXCR4 / Q000378:metabolism*; D019707:Receptors, Chemokine / Q000378:metabolism; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000187:drug effects*; D013696:Temperature
C515255:CXCL12 protein, human; D002412:Cations; D054377:Chemokine CXCL12; D018925:Chemokines; D019743:Chemokines, CXC; D015699:HIV Envelope Protein gp120; D008024:Ligands; D019718:Receptors, CXCR4; D019707:Receptors, Chemokine; D006147:Guanine; D006160:Guanosine Triphosphate