Dextran sulfate and heparin interact with CD4 molecules to inhibit the binding of coat protein (gp120) of HIV.
Dextran sulfate, heparin, and certain other sulfated polysaccharides potently inhibit the adsorption of HIV to CD4+ cells. The mechanism of this inhibition is unclear and, specifically, it is unknown if these agents act at the level of CD4-gp120 binding. For example, previous reports have demonstrated that dextran sulfate does not inhibit the cell surface binding of anti-CD4 mAb known to be directed at the gp120 binding site. In order to confirm and extend these observations, in the present study, it was shown that dextran sulfate does not inhibit the binding of OKT4A, OKT4C, Leu3a, or B66.6 to CD4+ cells as measured by cytofluorography. Next, recombinant forms of CD4 (rT4) and gp120 (rgp120) were utilized to directly study their molecular interaction in the absence of other viral or cellular structures. Reciprocal solid phase ELISA assays were developed to study directly the effects of sulfated polysaccharides on the binding of rT4 to immobilized rgp120 and vice versa. Dextran sulfate, heparin, and fucoidan, but not chondroitin sulfate, inhibited the binding of rgp120 to rT4. Importantly, dextran sulfate and heparin pre-treatment of immobilized rT4, but not immobilized rgp120, inhibited rT4-rgp120 binding. Taken together, these data suggest that while both sulfated polysaccharides and anti-CD4 mAb inhibit gp120 binding, the sulfated polysaccharides interact with sites on CD4 that are distinct from those with which the antibodies bind.
Lederman
S
S
Department of Medicine, Columbia University, College of Physicians and Surgeons, NY 10032.
Gulick
R
R
Chess
L
L
D000276:Adjuvants, Immunologic / Q000494:pharmacology / Q000502:physiology; D000911:Antibodies, Monoclonal / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology*; D001666:Binding Sites, Antibody / Q000187:drug effects; D001667:Binding, Competitive / Q000187:drug effects; D016264:Dextran Sulfate; D003911:Dextrans / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D006678:HIV / Q000378:metabolism*; D015699:HIV Envelope Protein gp120; D006493:Heparin / Q000494:pharmacology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology* / Q000502:physiology; D011134:Polysaccharides / Q000494:pharmacology; D011994:Recombinant Proteins / Q000378:metabolism; D012191:Retroviridae Proteins / Q000378:metabolism*
D000276:Adjuvants, Immunologic; D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D003911:Dextrans; D015699:HIV Envelope Protein gp120; D007166:Immunosuppressive Agents; D011134:Polysaccharides; D011994:Recombinant Proteins; D012191:Retroviridae Proteins; D006493:Heparin; D016264:Dextran Sulfate; C007789:fucoidan