Ha. Harrop et al., HEPARIN SPECIFICALLY INHIBITS BINDING OF V3 LOOP ANTIBODIES TO HIV-1 GP120, AN EFFECT POTENTIATED BY CD4 BINDING, AIDS, 8(2), 1994, pp. 183-192
Objective: To investigate the binding of the sulphated polysaccharides
, dextran sulphate and heparin, to CD4 and gp120 in order to examine t
he anti-HIV mechanisms of these compounds. Design: In order to study t
he molecular mechanisms involved, the binding of sulphated polysacchar
ides to recombinant (r) sCD4 and gp120 was investigated in solid-phase
binding studies that employed various monoclonal antibodies directed
against known epitopes on these protiens, including the V3 loop of gp1
20. Methods: The ability of sulphated polysaccharides to inhibit both
the binding of gp120 to CD4 and the binding of the monoclonal antibodi
es was investigated by enzyme-linked immunosorbent assays. Results: It
was demonstrated that dextran sulphate inhibits gp120-sCD4 binding at
concentrations of 100 mu g/ml, whereas heparin has no effect. Heparin
does, however, block the binding to rgp120 of monoclonal antibodies r
ecognizing epitopes in the V3 loop. Clinical low. molecular weight hep
arin preparations are as active as unfractionated heparin in this rega
rd. Pre-incubation of gp120 with excess sCD4 increases the potency of
heparin in blocking the binding of V3 loop monoclonals severalfold. Co
nclusions: 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 funct
ion only by interfering with events involving the V3 loop that occur p
rior to HIV fusion with the plasma membrane.