A SOLUBLE CD4 PROTEIN SELECTIVELY INHIBITS HIV REPLICATION AND SYNCYTIUM FORMATION

A SOLUBLE CD4 PROTEIN SELECTIVELY INHIBITS HIV REPLICATION AND SYNCYTIUM FORMATION
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DOI:
10.1038/331078a0
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发表时间:
1988-01-07
期刊:
影响因子:
64.8
通讯作者:
REINHERZ, EL
REINHERZ, EL
中科院分区:
综合性期刊1区
文献类型:
--
作者:
HUSSEY, RE;RICHARDSON, NE;REINHERZ, EL

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CD4 (T4)分子在参与II类MHC识别的T淋巴细胞亚群上表达1,2,并且可能是II类MHC一个或多个单态区域的生理受体(参考文献1-3)。CD4也作为人类免疫缺陷病毒(HIV)外包膜糖蛋白(gp120)的受体(参考文献4-9),对于病毒进入宿主细胞和膜融合至关重要,这有助于病毒的细胞间传播及其细胞病变效应10,11。我们使用杆状病毒表达系统产生了mg量的CD4亲水性细胞外片段。可溶性CD4浓度在纳摩尔范围内,与某些抗CD4单克隆抗体一样,通过结合表达gp120的细胞抑制合胞体形成和HIV感染。也许更重要的是,II类特异性t细胞的相互作用不受可溶性CD4蛋白的抑制,而它们实际上被等量的抗t4抗体所消除。这可能反映了CD4对gp120和II类MHC亲和力的实质性差异。
The CD4 (T4) molecule is expressed on a subset of T lymphocytes involved in class II MHC recognition1,2, and is probably the physiological receptor for one or more monomorphic regions of class II MHC (refs 1–3). CD4 also functions as a receptor for the human immunodeficiency virus (HIV) exterior envelope glycoprotein (gp120) (refs 4–9), being essential for virus entry into the host cell and for membrane fusion, which contributes to cell-to-cell transmission of the virus and to its cytopathic effects10,11. We have used a baculovirus expression system to generate mg quantities of a hydrophilic extracellular segment of CD4. Concentrations of soluble CD4 in the nanomolar range, like certain anti-CD4 monoclonal antibodies, inhibit syncytium formation and HIV infection by binding gp120-expressing cells. Perhaps more importantly, class II specific T-cell interactions are uninhibited by soluble CD4 protein, whereas they are virtually abrogated by equivalent amounts of anti-T4 antibody. This may reflect substantial differences in CD4 affinity for gp120 and class II MHC.