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Adenosine deaminase binding to human CD26 is inhibited by HIV-1 envelope glycoprotein gp120 and viral particles
A Valenzuela1, J Blanco, C Callebaut
1Department of Biochemistry and Molecular Biology, Faculty of Chemistry, University of Barcelona, Catalonia, Spain.
Insights
HIV-1 envelope glycoprotein gp120 inhibits adenosine deaminase (ADA) binding to CD26, a protein implicated in HIV infection. This interaction, occurring in both CD4+ and CD4- cells, may impact AIDS pathogenesis.
Area of Science:
- Immunology
- Virology
- Biochemistry
Background:
- CD26 is an adenosine deaminase (ADA)-binding protein implicated in HIV infection.
- Depletion of CD4+/CD26+ T lymphocytes and increased ADA levels correlate with AIDS progression.
Purpose of the Study:
- To investigate the interaction between HIV-1 gp120, ADA, and CD26.
- To determine the role of gp120 in inhibiting ADA binding to CD26.
Main Methods:
- Using human B and T cell lines, researchers studied the binding of 125I-labeled ADA to CD26.
- The effect of recombinant soluble HIV-1 gp120 and HIV-1 infectious particles on this binding was assessed.
- Monoclonal antibodies (mAbs) against CD4 and gp120 regions, as well as synthetic gp120 peptides, were used to map the interaction site.
Main Results:
- HIV-1 gp120 and infectious HIV-1 particles inhibited 125I-labeled ADA binding to CD26 in both CD4+ and CD4- cells.
- Anti-CD4 mAb did not affect this inhibition, while mAbs against gp120's V3 loop and C-terminal region abolished it.
- Synthetic peptides from the C3 region of gp120 significantly inhibited ADA binding to CD26.
Conclusions:
- HIV-1 gp120 directly or indirectly interacts with CD26, inhibiting ADA binding.
- This gp120-mediated inhibition of ADA-CD26 interaction may have implications for AIDS pathogenesis, given ADA's role in severe combined immunodeficiency.
Abstract:
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.