The HIV-1 gp120 inhibits the binding of adenosine deaminase to CD26 by a mechanism modulated by CD4 and CXCR4 expression.
HIV-1 external envelope glycoprotein gp120 inhibits adenosine deaminase (ADA) binding to its cell surface receptor in lymphocytes, CD26, by a mechanism that does not require the gp120-CD4 interaction. To further characterize this mechanism, we studied ADA binding to murine clones stably expressing human CD26 and/or human CD4, and transiently expressing human CXCR4. In this heterologous model, we show that both recombinant gp120 and viral particles from the X4 HIV-1 isolate IIIB inhibited the binding of ADA to wild-type or catalytically inactive forms of CD26. In cells lacking human CXCR4 expression, this gp120-mediated inhibition of ADA binding to human CD26 was completely dependent on the expression of human CD4. In contrast, when cells were transfected with human CXCR4 the inhibitory effect of gp120 was significantly enhanced and was not blocked by anti-CD4 antibodies. These data suggest that the interaction of gp120 with CD4 or CXCR4 is required for efficient inhibition of ADA binding to CD26, although in the presence of CXCR4 the interaction of gp120 with CD4 may be dispensable.
Blanco
J
J
Unité de Virologie et dImmunologie Cellulaire, ERS 572 CNRS, Institut Pasteur, 28 rue Dr. Roux, 75724 Paris Cedex 15, France. jblanco@ns.hugtip.scs.es
Valenzuela
A
A
Herrera
C
C
Lluís
C
C
Hovanessian
A G
AG
Franco
R
R
D000243:Adenosine Deaminase / Q000378:metabolism*; D058892:Adenosine Deaminase Inhibitors; D000818:Animals; D015704:CD4 Antigens / Q000235:genetics / Q000378:metabolism*; D002417:Cattle; D002460:Cell Line; D018819:Dipeptidyl Peptidase 4 / Q000235:genetics / Q000378:metabolism*; D005434:Flow Cytometry; D017353:Gene Deletion; D015699:HIV Envelope Protein gp120 / Q000378:metabolism*; D015497:HIV-1 / Q000502:physiology; D006801:Humans; D007457:Iodine Radioisotopes; D051379:Mice; D011485:Protein Binding; D019713:Receptors, CCR5 / Q000235:genetics / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D014162:Transfection
D058892:Adenosine Deaminase Inhibitors; D015704:CD4 Antigens; D015699:HIV Envelope Protein gp120; D007457:Iodine Radioisotopes; D019713:Receptors, CCR5; D019718:Receptors, CXCR4; D011994:Recombinant Proteins; D018819:Dipeptidyl Peptidase 4; D000243:Adenosine Deaminase