The crown and stem of the V3 loop play distinct roles in human immunodeficiency virus type 1 envelope glycoprotein interactions with the CCR5 coreceptor
The crown and stem of the V3 loop play distinct roles in human immunodeficiency virus type 1 envelope glycoprotein interactions with the CCR5 coreceptor
复制标题
DOI：
10.1128/jvi.76.17.8953-8957.2002
复制
发表时间：
2002-09-01
影响因子：
5.4
通讯作者：
Dragic, T
中科院分区：
文献类型：
--
作者：
Cormier, EG;Dragic, T
人类免疫缺陷病毒1型包膜糖蛋白gp120与CD4和CCR5辅助受体相互作用以介导病毒进入。gp120上的cd4诱导表面主要由V3环和C4结构域的残基组成，与CCR5相互作用。在本研究中，我们生成了包含嵌合V3环和/或缺失V3环的包膜糖蛋白，并研究了它们与CCR5氨基末端结构域（Nt）基巯基肽和细胞表面CCR5的结合，以及它们介导病毒进入的能力。因此，我们描绘了V3环的两个功能不同的区域，V3茎和V3冠。V3茎单独介导可溶性gp120与CCR5 Nt的结合，而V3茎和冠都需要可溶性gp120与细胞表面CCR5的结合。然而，在病毒粒子的情况下，仅V3冠就决定了辅助受体的使用。我们的数据支持两个位点gp120-CCR5结合模型，其中V3冠和茎与CCR5的不同区域相互作用以介导病毒进入。
Human immunodeficiency virus type 1 envelope glycoprotein gp120 interacts with CD4 and the CCR5 coreceptor in order to mediate viral entry. A CD4-induced surface on gp120, primarily composed of residues in the V3 loop and the C4 domain, interacts with CCR5. In the present study, we generated envelope glycoproteins comprising chimeric V3 loops and/or V3 loops with deletions and studied their binding to CCR5 amino-terminal domain (Nt)-based sulfopeptides and cell surface CCR5, as well as their ability to mediate viral entry. We thus delineated two functionally distinct domains of the V3 loop, the V3 stem and the V3 crown. The V3 stem alone mediates soluble gp120 binding to the CCR5 Nt. In contrast, both the V3 stem and crown are required for soluble gp120 binding to cell surface CCR5. Within the context of a virion, however, the V3 crown alone determines coreceptor usage. Our data support a two-site gp120-CCR5 binding model wherein the V3 crown and stem interact with distinct regions of CCR5 in order to mediate viral entry.