Novel anti-CD4 monoclonal antibodies separate human immunodeficiency virus infection and fusion of CD4+ cells from virus binding.
Novel anti-CD4 monoclonal antibodies separate human immunodeficiency virus infection and fusion of CD4+ cells from virus binding.
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DOI：
10.1084/jem.172.4.1233
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发表时间：
1990-10-01
期刊：
影响因子：
--
通讯作者：
Sattentau QJ
中科院分区：
文献类型：
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作者：
Healey D;Dianda L;Moore JP;McDougal JS;Moore MJ;Estess P;Buck D;Kwong PD;Beverley PC;Sattentau QJ
人类免疫缺陷病毒（HIV）通过CD4和病毒包膜糖蛋白gp120之间的相互作用与细胞结合。先前的研究将gp120的高亲和力结合位点定位在CD4的第一个区域，与该区域反应的单克隆抗体（mab）与gp120的结合竞争，从而阻断病毒的感染性和合胞体的形成。尽管详细了解了gp120与CD4的结合，但对导致膜融合和病毒进入的后续事件知之甚少。我们描述了两种新的单克隆抗体，它们与CD4的第三结构域反应，抑制病毒结合的后续步骤，这对HIV感染和细胞融合至关重要。这些抗体不抑制重组gp120或病毒与CD4的结合，而许多HIV分离株的感染和合胞体形成被阻断。这些发现表明，除了病毒结合外，CD4可能在膜融合中起积极作用。
Human immunodeficiency virus (HIV) binds to cells via an interaction between CD4 and the virus envelope glycoprotein, gp120. Previous studies have localized the high affinity binding site for gp120 to the first domain of CD4, and monoclonal antibodies (mAbs) reactive with this region compete with gp120 binding and thereby block virus infectivity and syncytium formation. Despite a detailed understanding of the binding of gp120 to CD4, little is known of subsequent events leading to membrane fusion and virus entry. We describe two new mAbs reactive with the third domain of CD4 that inhibit steps subsequent to virus binding critical for HIV infectivity and cell fusion. Binding of recombinant gp120 or virus to CD4 is not inhibited by these antibodies, whereas infection and syncytium formation by a number of HIV isolates are blocked. These findings demonstrate that in addition to virus binding, CD4 may have an active role in membrane fusion.