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 (AD A) binding to its cell surface receptor in lymphocytes, CD26, by a mechanis m that does not require the gp120-CD4 interaction. To further characterize this mechanism, we studied ADA binding to murine clones stably expressing h uman CD26 and/or human CD4, and transiently expressing human CXCR4, In this heterologous model, we show that both recombinant gp120 and viral particle s 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 expre ssion, this gp120-mediated inhibition of ADA binding to human CD26 was comp letely dependent on the expression of human CD4, In contrast, when cells me re transfected with human CXCR4 the inhibitory effect of gp120 was signific antly enhanced and was not blocked by anti-CD4 antibodies. These data sugge st that the interaction of gp120 with CD4 or CXCR4 is required for efficien t inhibition of ADA binding to CD26, although in the presence of CXCR4 the interaction of gp120 with CD4 may be dispensable. (C) 2000 Federation of Eu ropean Biochemical Societies. Published by Elsevier Science B.V. All rights reserved.