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.
Smith
R E
RE
Protek, Inc., Dublin, California 94568, USA. prototek@nothingbutnet.net
Talhouk
J W
JW
Brown
E E
EE
Edgar
S E
SE
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000595:Amino Acid Sequence; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D002240:Carbohydrate Sequence; D002412:Cations; D002462:Cell Membrane / Q000378:metabolism; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism*; D005260:Female; D015696:Gene Products, tat / Q000378:metabolism*; D015699:HIV Envelope Protein gp120 / Q000378:metabolism; D015497:HIV-1 / Q000378:metabolism; D006493:Heparin / Q000378:metabolism; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D019158:N-Acetylneuraminic Acid / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism; D010455:Peptides / Q000378:metabolism*; D011134:Polysaccharides / Q000378:metabolism; D051381:Rats; D019096:Vitronectin / Q000378:metabolism; D054322:tat Gene Products, Human Immunodeficiency Virus
D002412:Cations; D015696:Gene Products, tat; D015699:HIV Envelope Protein gp120; C059762:HIV envelope protein gp120 (305-321); D007527:Isoenzymes; D010446:Peptide Fragments; D010455:Peptides; D011134:Polysaccharides; D019096:Vitronectin; D054322:tat Gene Products, Human Immunodeficiency Virus; D006493:Heparin; C014420:colominic acid; D018819:Dipeptidyl Peptidase 4; D019158:N-Acetylneuraminic Acid