Multiple extracellular domains of CCR-5 contribute to human immunodeficiency virus type 1 entry and fusion
Multiple extracellular domains of CCR-5 contribute to human immunodeficiency virus type 1 entry and fusion
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CCR-5的多个胞外结构域有助于人类免疫缺陷病毒1型进入和融合
DOI：
10.1128/jvi.71.7.5003-5011.1997
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发表时间：
1997
影响因子：
5.4
通讯作者：
Paul R. Clapham
中科院分区：
文献类型：
--
作者：
L. Picard;Graham Simmons;Christine A. Power;Alexandra Meyer;R. Weiss;Paul R. Clapham
人类免疫缺陷病毒1型（HIV-1）的进入受病毒包膜糖蛋白（Env）与其受体相互作用的控制。HIV-1受体由两个分子组成，CD 4结合受体和辅助受体。七跨膜趋化因子受体CCR-5是HIV-1主要分离株使用的辅助受体之一。我们证明CCR-5的小鼠同源物（mCCR-5）不作为HIV-1辅助受体发挥作用。研究了一组人CCR-5和mCCR-5的嵌合体的Env诱导的细胞融合和HIV-1感染。使用HIV-1ADA包膜糖蛋白在合胞体形成试验中，我们表明，任何片段含有细胞外结构域的mCCR-5的人的对应物的替代是足以让Env诱导的融合。相反，任何片段含有人的细胞外结构域的小鼠对应物的替代没有导致辅助受体功能丧失。这些结果表明CCR-5的几个结构域参与辅助受体功能。此外，使用一个面板的主要nonsyncytium诱导和syncytium诱导分离物，使用CCR-5或CXCR-4和CCR-5作为辅助受体，我们发现，后者的双嗜性分离物是较不耐受CCR-5的变化比菌株更有限的辅助受体使用。因此，不同的菌株可能具有与CCR-5辅助受体相互作用的不同方式。
Human immunodeficiency virus type 1 (HIV-1) entry is governed by the interaction of the viral envelope glycoprotein (Env) with its receptor. The HIV-1 receptor is composed of two molecules, the CD4 binding receptor and a coreceptor. The seven-membrane-spanning chemokine receptor CCR-5 is one of the coreceptors used by primary isolates of HIV-1. We demonstrate that the mouse homolog of CCR-5 (mCCR-5) does not function as an HIV-1 coreceptor. A set of chimeras of human CCR-5 and mCCR-5 was studied for Env-induced cell fusion and HIV-1 infection. Using the HIV-1ADA envelope glycoprotein in a syncytium formation assay, we show that replacement of any fragment containing extracellular domains of mCCR-5 by its human counterparts is sufficient to allow Env-induced fusion. Conversely, replacement of any fragment containing human extracellular domains by its murine counterpart did not lead to coreceptor function loss. These results show that several domains of CCR-5 participate in coreceptor function. In addition, using a panel of primary nonsyncytium-inducing and syncytium-inducing isolates that use CCR-5 or both CXCR-4 and CCR-5 as coreceptors, we show that the latter dual-tropic isolates are less tolerant to changes in CCR-5 than strains with a more restricted coreceptor use. Thus, different strains are likely to have different ways of interacting with the CCR-5 coreceptor.