Quaternary Interaction of the HIV-1 Envelope Trimer with CD4 and Neutralizing Antibodies.

Quaternary Interaction of the HIV-1 Envelope Trimer with CD4 and Neutralizing Antibodies.
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DOI:
10.3390/v13071405
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发表时间:
2021-07-20
期刊:
Viruses
影响因子:
--
通讯作者:
Lusso P
Lusso P
中科院分区:
其他
文献类型:
--
作者:
Liu Q;Zhang P;Lusso P

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HIV-1 进入宿主细胞是由病毒包膜 (Env) 刺突与 CD4 受体相互作用启动的。在此过程中,刺突经历一系列构象变化,最终导致位于跨膜糖蛋白 gp41 N 末端的融合肽暴露。最近的结构和功能研究为不同阶段的 Env 与 CD4 的相互作用提供了重要的见解。然而,详细阐明 CD4 接触的最早事件及其对 Env 构象的直接影响仍然是研究的挑战。在这里,我们总结了 HIV-1 Env 中 CD4 结合位点四级性质的发现以及四级接触在与 CD4 受体功能相互作用中的作用。我们根据现有知识提出了这种初始接触的两种模型,并讨论了如何更好地理解四元相互作用可以导致改进针对 CD4 结合位点的免疫原和抗体。
The entry of HIV-1 into host cells is initiated by the interaction of the viral envelope (Env) spike with the CD4 receptor. During this process, the spike undergoes a series of conformational changes that eventually lead to the exposure of the fusion peptide located at the N-terminus of the transmembrane glycoprotein, gp41. Recent structural and functional studies have provided important insights into the interaction of Env with CD4 at various stages. However, a fine elucidation of the earliest events of CD4 contact and its immediate effect on the Env conformation remains a challenge for investigation. Here, we summarize the discovery of the quaternary nature of the CD4-binding site in the HIV-1 Env and the role of quaternary contact in the functional interaction with the CD4 receptor. We propose two models for this initial contact based on the current knowledge and discuss how a better understanding of the quaternary interaction may lead to improved immunogens and antibodies targeting the CD4-binding site.
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