The significance of hypersialylation of dipeptidyl peptidase IV (CD26) in the inhibition of its activity by Tat and other cationic peptides. CD26: a subverted adhesion molecule for HIV peptide binding.

The functionality of DPP-IV, purified from human placenta and isolated from CD4+/CD26+ T cells of noninfected and HIV-1-infected individuals, was investigated as to its ability to bind certain specific peptides. Using isoelectric focusing and the specificity of substrate-impregnated overlay membranes, we found that DPP-IV from term placenta and from T cells of HIV-infected individuals was significantly more sialylated compared with enzyme isozyme patterns of other tissues. We report here that (1) the number of isoforms of DPP-IV and extent of sialylation are critical to function and peptide binding; (2) the number of sialylated isoforms isolated from PBMCs increases significantly with age greater than 40 years; (3) hypersialylation by extreme anionic isoforms is highly associated with HIV infection and pathognomonic to remaining CD4+ cells in overt AIDS; and (4) highly sialylated DPP-IV is more significantly inhibited by Tat and cationic peptides. We conclude that hypersialylation of DPP-IV modifies surface charge of the CD26 antigen, promoting binding of HIV peptides through their cationic domains to the sialic acid residues of DPP-IV, and that certain HIV moieties are likely to engage this phenomenon as an auxiliary adhesion mechanism to fuse with cells. Furthermore, as a consequence of this occurrence, DPP-IV enzymatic activity can be significantly reduced, competitively.