Department of Medicine, Alberta Respiratory Centre, University of Alberta, Edmonton, AB T6G 2S2, Canada.
Laboratory Research and Biotechnology, Department of Biological Sciences Technology, Northern Alberta Institute of Technology, Edmonton, AB T5G 2R1, Canada.
Viruses. 2021 Jul 31;13(8):1515. doi: 10.3390/v13081515.
Despite type 1 human immunodeficiency virus (HIV-1) being discovered in the early 1980s, significant knowledge gaps remain in our understanding of the superstructure of the HIV-1 matrix (MA) shell. Current viral assembly models assume that the MA shell originates via recruitment of group-specific antigen (Gag) polyproteins into a hexagonal lattice but fails to resolve and explain lattice overlapping that occurs when the membrane is folded into a spherical/ellipsoidal shape. It further fails to address how the shell recruits, interacts with and encompasses the viral spike envelope (Env) glycoproteins. These Env glycoproteins are crucial as they facilitate viral entry by interacting with receptors and coreceptors located on T-cells. In our previous publication, we proposed a six-lune hosohedral structure, snowflake-like model for the MA shell of HIV-1. In this article, we improve upon the six-lune hosohedral structure by incorporating into our algorithm the recruitment of complete Env glycoproteins. We generated the Env glycoprotein assembly using a combination of predetermined Env glycoprotein domains from X-ray crystallography, nuclear magnetic resonance (NMR), cryoelectron tomography, and three-dimensional prediction tools. Our novel MA shell model comprises 1028 MA trimers and 14 Env glycoproteins. Our model demonstrates the movement of Env glycoproteins in the interlunar spaces, with effective clustering at the fusion hub, where multiple Env complexes bind to T-cell receptors during the process of viral entry. Elucidating the HIV-1 MA shell structure and its interaction with the Env glycoproteins is a key step toward understanding the mechanism of HIV-1 entry.
尽管 1 型人类免疫缺陷病毒 (HIV-1) 早在 20 世纪 80 年代就被发现，但我们对 HIV-1 基质 (MA) 壳的超结构仍存在很大的认识差距。目前的病毒组装模型假设 MA 壳通过募集特定于群体的抗原 (Gag) 多蛋白进入六方晶格，但无法解决和解释当膜折叠成球形/椭圆形时发生的晶格重叠。它进一步未能解决外壳如何招募、相互作用和包含病毒刺突包膜 (Env) 糖蛋白。这些 Env 糖蛋白至关重要，因为它们通过与 T 细胞上的受体和共受体相互作用促进病毒进入。在我们之前的出版物中，我们提出了 HIV-1 MA 壳的六棱拟十二面体结构、雪花状模型。在本文中，我们通过将完整的 Env 糖蛋白募集纳入我们的算法来改进六棱拟十二面体结构。我们使用来自 X 射线晶体学、核磁共振 (NMR)、冷冻电子断层扫描和三维预测工具的预定 Env 糖蛋白结构域的组合来生成 Env 糖蛋白组装。我们的新型 MA 壳模型由 1028 个 MA 三聚体和 14 个 Env 糖蛋白组成。我们的模型展示了 Env 糖蛋白在月球间的运动，在融合枢纽处有效聚集，在病毒进入过程中，多个 Env 复合物与 T 细胞受体结合。阐明 HIV-1 MA 壳结构及其与 Env 糖蛋白的相互作用是理解 HIV-1 进入机制的关键步骤。
