Adenosine deaminase binding to human CD26 is inhibited by HIV-1 envelope glycoprotein gp120 and viral particles.
CD26, known to be the adenosine deaminase (ADA)-binding protein, has been implicated in HIV infection. Several studies have revealed a correlation between depletion of CD4+/CD26+ T lymphocytes, increased serum levels of ADA, and the evolution of AIDS in infected individuals. We show that in human B and T cell lines, irrespective of CD4 expression, 125I-labeled ADA binding to CD26 is inhibited by recombinant soluble HIV-1 envelope glycoprotein gp120 and by HIV-1 infectious particles. Accordingly, an anti-CD4 mAb, which inhibits the binding of gp120 to CD4 and blocks viral infection, did not affect inhibition of 125I-labeled ADA binding to CD26 by HIV particles. On the other hand, mAbs directed against the V3 loop and the C-terminal region of gp120 abolished completely the inhibitory effect. Overlapping synthetic peptides covering the entire gp120 sequence were tested to map the region in gp120 responsible for ADA binding inhibition. Only peptides in the C3 region significantly inhibited the binding of ADA to CD26. These results provide indirect evidence for the interaction of gp120 with CD26 and indicate that a specific function of gp120 is the inhibition of ADA binding to CD26 in both CD4+ and CD4- cells. Because ADA deficiency leads to severe combined immunodefiency syndrome, it remains possible that HIV particle-mediated blockade of ADA-CD26 interaction may have significant consequences in the pathogenesis of AIDS.
Valenzuela
A
A
Department of Biochemistry and Molecular Biology, Faculty of Chemistry, University of Barcelona, Catalonia, Spain.
Blanco
J
J
Callebaut
C
C
Jacotot
E
E
Lluis
C
C
Hovanessian
A G
AG
Franco
R
R
D000243:Adenosine Deaminase / Q000378:metabolism*; D000595:Amino Acid Sequence; D001402:B-Lymphocytes / Q000276:immunology* / Q000821:virology; D002460:Cell Line; D018819:Dipeptidyl Peptidase 4 / Q000276:immunology* / Q000378:metabolism; D015699:HIV Envelope Protein gp120 / Q000276:immunology / Q000494:pharmacology*; D006801:Humans; D008969:Molecular Sequence Data; D011485:Protein Binding / Q000187:drug effects; D013601:T-Lymphocytes / Q000276:immunology* / Q000821:virology; D014771:Virion / Q000276:immunology*
D015699:HIV Envelope Protein gp120; D018819:Dipeptidyl Peptidase 4; D000243:Adenosine Deaminase