HEPARIN SPECIFICALLY INHIBITS BINDING OF V3 LOOP ANTIBODIES TO HIV-1 GP120, AN EFFECT POTENTIATED BY CD4 BINDING
HEPARIN SPECIFICALLY INHIBITS BINDING OF V3 LOOP ANTIBODIES TO HIV-1 GP120, AN EFFECT POTENTIATED BY CD4 BINDING
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DOI：
10.1097/00002030-199402000-00005
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发表时间：
1994-02-01
期刊：
影响因子：
3.8
通讯作者：
RIDER, CC
中科院分区：
文献类型：
--
作者：
HARROP, HA;COOMBE, DR;RIDER, CC
目的：研究硫酸化多糖、硫酸葡聚糖和肝素与CD 4和gp 120的结合，以检查这些化合物的抗HIV机制。设计：为了研究相关的分子机制，在固体中研究了硫酸化多糖与重组（r）sCD 4和gp 120的结合，采用针对这些蛋白上的已知表位（包括gp 120的V3环）的各种单克隆抗体进行阶段结合研究。通过酶联免疫吸附试验研究硫酸化多糖抑制gp 120与CD 4结合和单克隆抗体结合的能力。结果表明，硫酸葡聚糖在100 μ g/ml浓度下抑制gp 120-sCD 4结合，而肝素则没有作用。然而，肝素确实阻断识别V3环中表位的单克隆抗体与rgp 120的结合。临床低。在这方面，分子量肝素制剂与未分级肝素一样具有活性。gp 120与过量的sCD 4预孵育增加了肝素在阻断V3环单克隆抗体结合的效力severalfolds.Conclusions：肝素和硫酸葡聚糖的作用模式不同。硫酸葡聚糖既抑制CD 4-gp 120结合，又与gp 120的V3环结合。然而，肝素更具选择性，似乎仅通过干扰HIV与质膜融合之前发生的涉及V3环的事件发挥作用。
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 protiens, 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 mu g/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.