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美国耶鲁大学医学院Walther Mothes等研究人员合作发现，HIV-1 Env三聚体不对称地与膜上的CD4受体接触。2023年11月22日，《自然》期刊在线发表了这一成果。

研究人员表示，人类免疫缺陷病毒1（HIV-1）的感染是通过病毒包膜糖蛋白（Env）与细胞表面受体CD4结合开始的。虽然已经确定了Env与CD4可溶性结构域复合物的高分辨率结构，但对其在原生膜上的结合过程了解较少。

研究人员使用低温电子断层扫描技术来监测了HIV-1与CD4呈递病毒样颗粒之间形成的膜-膜界面上Env-CD4的相互作用。Env-CD4复合物组织成簇和环，使对立的膜更紧密地结合在一起。Env-CD4成簇取决于囊膜成熟度。子图平均化和分类显示，Env与一个、两个以及最后三个CD4分子结合，之后Env采用开放状态。这些数据表明，与一个和两个CD4分子结合的不对称HIV-1 Env三聚体是病毒与宿主细胞膜结合过程中可检测到的中间产物，这可能会对抗体介导的免疫反应和疫苗免疫原设计产生影响。

附：英文原文

Title: HIV-1 Env trimers asymmetrically engage CD4 receptors in membranes

Author: Li, Wenwei, Qin, Zhuan, Nand, Elizabeth, Grunst, Michael W., Grover, Jonathan R., Bess, Julian W., Lifson, Jeffrey D., Zwick, Michael B., Tagare, Hemant D., Uchil, Pradeep D., Mothes, Walther

Issue&Volume: 2023-11-22

Abstract: Human immunodeficiency virus 1 (HIV-1) infection is initiated by binding of the viral envelope glycoprotein (Env) to the cell-surface receptor CD41–4. Although high-resolution structures of Env in a complex with the soluble domains of CD4 have been determined, the binding process is less understood in native membranes5–13. Here we used cryo-electron tomography to monitor Env–CD4 interactions at the membrane–membrane interfaces formed between HIV-1 and CD4-presenting virus-like particles. Env–CD4 complexes organized into clusters and rings, bringing the opposing membranes closer together. Env–CD4 clustering was dependent on capsid maturation. Subtomogram averaging and classification revealed that Env bound to one, two and finally three CD4 molecules, after which Env adopted an open state. Our data indicate that asymmetric HIV-1 Env trimers bound to one and two CD4 molecules are detectable intermediates during virus binding to host cell membranes, which probably has consequences for antibody-mediated immune responses and vaccine immunogen design. HIV-1 Env trimers bound to one, two and three CD4 molecules are observed at membrane–membrane interfaces between HIV-1 and CD4-decorated virus-like particles.

DOI: 10.1038/s41586-023-06762-6

Source: https://www.nature.com/articles/s41586-023-06762-6

Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
官方网址：http://www.nature.com/
投稿链接：http://www.nature.com/authors/submit_manuscript.html