Epitope mapping and characterization of a novel CD4-induced human monoclonal antibody capable of neutralizing primary HIV-1 strains
Epitope mapping and characterization of a novel CD4-induced human monoclonal antibody capable of neutralizing primary HIV-1 strains
复制标题
DOI：
10.1016/s0042-6822(03)00521-x
复制
发表时间：
2003-10-10
期刊：
影响因子：
3.7
通讯作者：
Sodroski, J
中科院分区：
文献类型：
--
作者：
Xiang, SH;Wang, LP;Sodroski, J
人类免疫缺陷病毒（HIV-1）通过将其gp 120外包膜糖蛋白与CD 4和趋化因子受体之一CCR 5或CXCR 4结合进入靶细胞。CD 4诱导的（CD 4 i）抗体在CD 4结合后更有效地结合gp 120，并阻断与趋化因子受体的相互作用。CD 4 i抗体的实例是有限的，并且CD 4 i抗体的原型仅表现出针对初级临床HIV-1分离株的弱中和活性。在这里，我们报告了一种新的抗体，E51，表现出CD 4诱导的结合gp 120和中和的主要HIV-1比原型CD 4 i抗体更有效。E51抗体阻断gp 120-CD 4复合物与CCR 5的相互作用，并结合由β 19链和周围结构组成的高度保守的基本gp 120元件。因此，在原代HIV-1分离株上，先前与趋化因子受体结合有关的gp 120区域可被CD 4 i抗体亚组接近。(C)2003年爱思唯尔公司All rights reserved.
Human immunodeficiency virus (HIV-1) enters target cells by binding its gp120 exterior envelope glycoprotein to CD4 and one of the chemokine receptors, CCR5 or CXCR4. CD4-induced (CD4i) antibodies bind gp120 more efficiently after CD4 binding and block the interaction with the chemokine receptor. Examples of CD4i antibodies are limited, and the prototypes of the CD4i antibodies exhibit only weak neutralizing activity against primary, clinical HIV-1 isolates. Here we report the identification of a novel antibody, E51, that exhibits CD4-induced binding to gp120 and neutralizes primary HIV-1 more efficiently than the prototypic CD4i antibodies. The E51 antibody blocks the interaction of gp120-CD4 complexes with CCR5 and binds to a highly conserved, basic gp120 element composed of the beta19-strand and surrounding structures. Thus, on primary HIV-1 isolates, this gp120 region, which has been previously implicated in chemokine receptor binding, is accessible to a subset of CD4i antibodies. (C) 2003 Elsevier Inc. All rights reserved.