HIV-1 p17 binds heparan sulfate proteoglycans to activated CD4(+) T cells.
We have previously shown that HIV-1 p17 binds to activated peripheral blood mononuclear cells and enhances secretion of pro-inflammatory cytokines, but we were unable to define a ligand on activated cells. In this work we evaluate the hypothesis that HIV-1 p17 may be a heparin/heparan sulfate-binding protein. HIV-1 p17 contains C- and N-terminal sequences with positively charged residues and a consensus cluster for heparin binding. We demonstrated by affinity chromatography that HIV-1 p17 binds strongly to heparin-agarose at physiological pH. Soluble heparins and heparan sulfate but not chondroitin 4-sulfate and dextran sulfate inhibit binding of HIV-1 p17 to heparin solid phase and to activated CD4(+) T cells. Furthermore the inhibition of cell sulfatation by chlorate treatment completely counteracts HIV-1 p17 binding to activated cells. These results indicate for the first time that HIV-1 p17 can be ascribed to the heparin binding protein family and suggest that this interaction might play a key role in the ability of the protein to induce an inflammatory effect on activated cells.
Institute of Microbiology, University of Brescia Medical School, Brescia, Italy. claudio.poiesi@tiscali.it
Claudio
C
Poiesi
Maria A
MA
De Francesco
Manuela
M
Baronio
Nino
N
Manca
D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D002704:Chlorates / Q000494:pharmacology; D002846:Chromatography, Affinity; D004797:Enzyme-Linked Immunosorbent Assay; D006025:Glycosaminoglycans / Q000378:metabolism; D015488:HIV Antigens / Q000276:immunology / Q000378:metabolism*; D019812:Heparan Sulfate Proteoglycans / Q000276:immunology / Q000378:metabolism*; D006493:Heparin / Q000032:analysis / Q000494:pharmacology; D006801:Humans; D008213:Lymphocyte Activation; D018613:Microscopy, Confocal; D011485:Protein Binding / Q000187:drug effects; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000276:immunology / Q000378:metabolism*
D002704:Chlorates; D006025:Glycosaminoglycans; D015488:HIV Antigens; D019812:Heparan Sulfate Proteoglycans; D054301:gag Gene Products, Human Immunodeficiency Virus; C054858:p17 protein, Human Immunodeficiency Virus Type 1; D006493:Heparin