Heparin specifically inhibits binding of V3 loop antibodies to HIV-1 gp120, an effect potentiated by CD4 binding.

Important note: Information in this article was accurate in 1994. The state of the art may have changed since the publication date.

Heparin specifically inhibits binding of V3 loop antibodies to HIV-1 gp120, an effect potentiated by CD4 binding.

AIDS. 1994 Feb;8(2):183-92. Unique Identifier : AIDSLINE MED/94318201
Harrop HA; Coombe DR; Rider CC; Department of Biochemistry, Royal Holloway, University of London,; Egham, Surrey, UK.

Abstract: OBJECTIVE: To investigate the binding of the sulphated polysaccharides, dextran sulphate and heparin, to CD4 and gp120 in order to examine the anti-HIV mechanisms of these compounds. DESIGN: In order to study the molecular mechanisms involved, the binding of sulphated polysaccharides to recombinant (r) sCD4 and gp120 was investigated in solid-phase binding studies that employed various monoclonal antibodies directed against known epitopes on these proteins, including the V3 loop of gp120. METHODS: The ability of sulphated polysaccharides to inhibit both the binding of gp120 to CD4 and the binding of the monoclonal antibodies was investigated by enzyme-linked immunosorbent assays. RESULTS: It was demonstrated that dextran sulphate inhibits gp120-sCD4 binding at concentrations of 100 micrograms/ml, whereas heparin has no effect. Heparin does, however, block the binding to rgp120 of monoclonal antibodies recognizing epitopes in the V3 loop. Clinical low molecular weight heparin preparations are as active as unfractionated heparin in this regard. Pre-incubation of gp120 with excess sCD4 increases the potency of heparin in blocking the binding of V3 loop monoclonals severalfold. CONCLUSIONS: The modes of action of heparin and dextran sulphate differ. Dextran sulphate both inhibits CD4-gp120 binding and binds to the V3 loop of gp120. However, heparin is more selective and appears to function only by interfering with events involving the V3 loop that occur prior to HIV fusion with the plasma membrane.

Keywords: Antibodies, Monoclonal/*IMMUNOLOGY/METABOLISM Antibody Specificity Antigen-Antibody Reactions/*DRUG EFFECTS Antigens, CD4/*METABOLISM Comparative Study Dextran Sulfate/PHARMACOLOGY Enoxaparin/PHARMACOLOGY Enzyme-Linked Immunosorbent Assay Heparin/*PHARMACOLOGY Human HIV Antibodies/*IMMUNOLOGY/METABOLISM HIV Envelope Protein gp120/*IMMUNOLOGY/METABOLISM HIV-1/*IMMUNOLOGY Membrane Fusion Peptide Fragments/*IMMUNOLOGY/METABOLISM Protein Binding/DRUG EFFECTS Recombinant Proteins/IMMUNOLOGY/METABOLISM Support, Non-U.S. Gov't JOURNAL ARTICLE

941130
M94B0773

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