HIV REQUIRES MULTIPLE GP120 MOLECULES FOR CD4-MEDIATED INFECTION
HIV REQUIRES MULTIPLE GP120 MOLECULES FOR CD4-MEDIATED INFECTION
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DOI：
10.1038/346277a0
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发表时间：
1990-07-19
期刊：
影响因子：
64.8
通讯作者：
NARA, PL
中科院分区：
文献类型：
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作者：
LAYNE, SP;MERGES, MJ;NARA, PL
糖蛋白gp 120与T细胞表面受体CD 4的结合是人类免疫缺陷病毒（HIV）1- 5依赖于CD 4感染靶细胞的关键步骤。因此，阻断病毒表面的部分或全部gp 120分子应抑制感染。因此，竞争性受体抑制剂，如可溶性合成CD 4（sCD 4），合成CD 4肽和免疫球蛋白，已经在体外6 - 17和体内8 - 20进行了研究，但对这些抑制剂的分子机制知之甚少。我们现在已经定量研究了可溶性CD 4的阻断作用，希望深入了解病毒结合、吸附和渗透的复杂过程。在低sCD 4浓度下，在三种HIV毒株中的抑制与gp 120的结合成比例。HIV-2NIHZ的生物结合常数（gp 120-sCD 4 Kassoc）为（8.5±0.5）× 107 M −1，而HIV-1HXB 3的Kassoc为（1.4±0.2）× 109 M − 1，HIV-1 MN的Kassoc为（1.7±0.1）× 109 M − 1，两者相差15-20倍。对于所有三种病毒株，来自感染性试验的生物Kassoc与化学Kassoc相当。然而，sCD 4在高浓度下的抑制作用不能完全用与gp 120结合的简单比例来解释。阻断感染的正协同作用发生在大约一半的病毒gp 120分子被占据后，并且对于所有三种病毒株都是相同的，尽管在Kaspersky中存在很大差异。我们直接从感染性试验中测量病毒细胞受体Kassoc的方法适用于免疫球蛋白、其他病毒以及使用原代或转化细胞系的试验。
BINDING of glycoprotein gp120 to the T cell-surface receptor CD4 is a crucial step in CD4-dependent infection of a target cell by the human immunodeficiency virus (HIV)1–5.Blocking some or all gp120 molecules on the viral surface should therefore inhibit infection. Consequently, competitive receptor inhibitors, such as soluble synthetic CD4 (sCD4), synthetic CD4 peptides and immunoglobulins, have been investigatedin vitro6–17andin vivol8–20but little is known about the molecular mechanisms of these inhibitors. We have now quantitatively examined blocking by soluble CD4 in the hope of gaining insight into the complex process of viral binding, adsorption and penetration. At low sCD4 concentrations, the inhibition in three HIV strains is proportional to the binding of gp120. The biological association constant (gp120-sCD4 Kassoc) for HIV-2NIHZis (8.5±0.5)×107M−1, whereas Kassocfor HIV-1HXB3(1.4±0.2) and HIV-1MN(1.7±0.1)×109M−1are 15–20-fold larger. For all three viral strains, the biologicalKassocfrom infectivity assays is comparable to the chemicalKassoc.The inhibitory action of sCD4 at high concentrations, however, is not fully explained by simple proportionality with the binding to gp120. Positive synergy in blocking of infection occurs after about half the viral gp120s molecules are occupied, and is identical for all three viral strains, despite the large differences inKassoc. Our method of measuring the viral-cell receptorKassocdirectly from infectivity assays is applicable to immunoglobulins, to other viruses and to assays using primary or transformed cell lines.