Specific interaction of CXCR4 with CD4 and CD8alpha: functional analysis of the CD4/CXCR4 interaction in the context of HIV-1 envelope glycoprotein-mediated membrane fusion.
We investigated possible interactions between HIV-1 receptor (CD4) and the main coreceptors CXCR4 and CCR5. We found that CD4 and CXCR4 coexpressed in 293T cells form a complex that can be immunoprecipitated with antibodies directed against the extracellular domain of either protein. Mutagenesis revealed that the CD4/CXCR4 interaction maps to two previously uncharacterized basic motifs in the cytoplasmic domain of CD4. HIV-1 envelope glycoprotein-mediated membrane fusion was found to be independent of the ability of CD4 and CXCR4 to interact, whether fusion was studied in a virus-cell or a cell-cell model. However, this interaction might explain the adaptation of HIV-1 to CXCR4 as an alternative to CCR5. We found that CXCR4 also interacts with the cytoplasmic domain of CD8alpha in a way that is similar to the CD4/CXCR4 interaction. The CD4/CXCR4 and CD8alpha/CXCR4 interactions may thus be involved in cellular signaling pathways shared by the CD4 and CD8alpha molecules.
Basmaciogullari
Stéphane
S
Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, MA 02115, USA. basmaciogullari@cochin.inserm.fr
Pacheco
Beatriz
B
Bour
Stephan
S
Sodroski
Joseph
J
D015704:CD4 Antigens / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D016827:CD8 Antigens / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D015497:HIV-1 / Q000378:metabolism*; D006801:Humans; D008561:Membrane Fusion / Q000502:physiology*; D016297:Mutagenesis, Site-Directed; D017434:Protein Structure, Tertiary; D019713:Receptors, CCR5 / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D014759:Viral Envelope Proteins / Q000378:metabolism*
D015704:CD4 Antigens; D016827:CD8 Antigens; D019713:Receptors, CCR5; D019718:Receptors, CXCR4; D011993:Recombinant Fusion Proteins; D014759:Viral Envelope Proteins