The antigenic structure of the HIV gp120 envelope glycoprotein
The antigenic structure of the HIV gp120 envelope glycoprotein
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DOI：
10.1038/31514
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发表时间：
1998-06-18
期刊：
影响因子：
64.8
通讯作者：
Sodroski, JG
中科院分区：
文献类型：
--
作者：
Wyatt, R;Kwong, PD;Sodroski, JG
人类免疫缺陷病毒HIV-1在人类中建立持续感染，导致获得性免疫缺陷综合征（AIDS）。HIV-1包膜糖蛋白gp 120和gp 41组装成三聚体复合物，介导病毒进入靶细胞（1）。HIV-1的进入依赖于gp 120外被膜糖蛋白与细胞上的受体、CD 4和趋化因子受体家族成员的顺序相互作用（2-4）。gp 120糖蛋白，它可以从包膜复合物脱落，在自然感染期间激发病毒中和和非中和抗体。缺乏中和活性的抗体通常针对组装三聚体上封闭且仅在脱落时暴露的gp 120区域（5，6）。相反，中和抗体必须接近功能性包膜糖蛋白复合物（7），并且通常识别受体结合区附近的保守或可变表位（8-11）。在这里，我们描述了gp 120上保守中和表位的空间组织，使用表位图结合三元复合物的X射线晶体结构，该三元复合物包括gp 120核心、CD 4和中和抗体（12）。预测的三聚体中gp 120的可及表面的大部分由围绕受体结合区的可变的、高度糖基化的核心和环结构组成。了解HIV-1逃避体液免疫反应能力的结构基础将有助于疫苗的设计。
The human immunodeficiency virus HIV-1 establishes persistent infections in humans which lead to acquired immunodeficiency syndrome (AIDS). The HIV-1 envelope glycoproteins, gp120 and gp41, are assembled into a trimeric complex that mediates virus entry into target cells(1). HIV-1 entry depends on the sequential interaction of the gp120 exterior envelope glycoprotein with the receptors on the cell, CD4 and members of the chemokine receptor family(2-4). The gp120 glycoprotein, which can be shed from the envelope complex, elicits both virus-neutralizing and non-neutralizing antibodies during natural infection. Antibodies that lack neutralizing activity are often directed against the gp120 regions that are occluded on the assembled trimer and which are exposed only upon shedding(5,6). Neutralizing antibodies, by contrast, must access the functional envelope glycoprotein complex(7) and typically recognize conserved or variable epitopes near the receptor-binding regions(8-11). Here we describe the spatial organization of conserved neutralization epitopes on gp120, using epitope maps in conjunction with the X-ray crystal structure of a ternary complex that includes a gp120 core, CD4 and a neutralizing antibody(12). A large fraction of the predicted accessible surface of gp120 in the trimer is composed of variable, heavily glycosylated core and loop structures that surround the receptor-binding regions. Understanding the structural basis for the ability of HIV-1 to evade the humoral immune response should assist in the design of a vaccine.