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M9490156.TXT
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1994-09-03
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Document 0156
DOCN M9490156
TI Heparin specifically inhibits binding of V3 loop antibodies to HIV-1
gp120, an effect potentiated by CD4 binding.
DT 9411
AU Harrop HA; Coombe DR; Rider CC; Department of Biochemistry, Royal
Holloway, University of London,; Egham, Surrey, UK.
SO AIDS. 1994 Feb;8(2):183-92. Unique Identifier : AIDSLINE MED/94318201
AB 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.
DE 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
SOURCE: National Library of Medicine. NOTICE: This material may be
protected by Copyright Law (Title 17, U.S.Code).