HIV-1 envelope (Env) N-glycosylation impact virus-cell entry and immune evasion. How each glycan interacts to shape the Env-protein-sugar complex and affects Env function is not well understood. Here, analysis of two Env variants from the same donor, with differing functional characteristics and N-glycosylation-site composition, revealed that changes to key N-glycosylation sites affected the Env structure at distant locations and had a ripple effect on Env-wide glycan processing, virus infectivity, antibody recognition, and virus neutralization. Specifically, the N262 glycan, although not in the CD4-binding site, modulated Env binding to the CD4 receptor, affected Env recognition by several glycan-dependent neutralizing antibodies, and altered site-specific glycosylation heterogeneity, with, for example, N448 displaying limited glycan processing. Molecular-dynamic simulations visualized differences in glycan density and how specific oligosaccharide positions can move to compensate for a glycan loss. This study demonstrates how changes in individual glycans can alter molecular dynamics, processing, and function of the Env-glycan shield.

HIV-1 包膜 (Env) N-糖基化影响病毒细胞进入和免疫逃避。每个聚糖如何相互作用形成 Env-蛋白质-糖复合物并影响 Env 功能尚不清楚。在这里，对来自同一供体的两个具有不同功能特征和 N-糖基化位点组成的 Env 变体的分析表明，关键 N-糖基化位点的变化影响了远处位置的 Env 结构，并对 Env 范围内的聚糖产生了连锁反应处理、病毒感染性、抗体识别和病毒中和。具体而言，N262 聚糖虽然不在 CD4 结合位点，但可调节 Env 与 CD4 受体的结合，影响几种聚糖依赖性中和抗体对 Env 的识别，并改变位点特异性糖基化异质性，例如，N448 显示有限的糖基化异质性。聚糖加工。分子动力学模拟可视化了聚糖密度的差异以及特定寡糖位置如何移动以补偿聚糖损失。这项研究展示了单个聚糖的变化如何改变分子动力学、加工和环境聚糖屏蔽的功能。