Liu Mengying, Wu Xuesheng, van de Garde Martijn D B, Narimatsu Yoshiki, van Kuppeveld Frank J M, Clausen Henrik, de Haan Cornelis A M, de Vries Erik
Virology Section, Division of Infectious Diseases and Immunology, Department of Biomolecular Health Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, the Netherlands.
Copenhagen Center for Glycomics, Department of Cellular and Molecular Medicine, Faculty of Health Sciences, University of Copenhagen, Blegdamsvej 3, Copenhagen, Denmark.
iScience. 2025 May 3;28(6):112549. doi: 10.1016/j.isci.2025.112549. eCollection 2025 Jun 20.
Influenza A viruses multivalently engages sialoglycan attachment factors. Synthetic glycan arrays provide meticulous insight into primary binding specificity but do not capture dynamic post-binding virus-receptor interactions leading to cell entry. Establishing an HEK293 cell-based array of genetically dissected sialoglycan assemblies enabled screening of the complete interaction cascade from binding to infection, at physiologically relevant low virus doses. Screening forty years of H3N2 receptor binding evolution showed that besides N-glycans, deemed as principal receptors for primary attachment, specific O-glycans or glycosphingolipids independently supported all steps from primary binding to entry. For all three glycoconjugate classes, receptor preferences gradually evolved toward utilization of human-type α2-6-linked sialic acid receptors, followed by regaining use of avian-type α2-3-linked receptors after 1995. The screen identified a lack of quantitative correlation between binding and infection efficiency, suggesting specific receptor requirements beyond attachment. Virus-glycan interactions and other sialoglycan-dependent interactions with cells can be functionally analyzed using this system.
甲型流感病毒多价结合唾液酸聚糖附着因子。合成聚糖阵列能深入洞察主要结合特异性，但无法捕捉导致细胞进入的动态结合后病毒-受体相互作用。建立基于人胚肾293细胞的经基因剖析的唾液酸聚糖组装体阵列，能够在生理相关的低病毒剂量下，筛选从结合到感染的完整相互作用级联。对40年H3N2受体结合进化的筛选表明，除了被视为主要附着受体的N-聚糖外，特定的O-聚糖或糖鞘脂独立支持从主要结合到进入的所有步骤。对于所有三类糖缀合物，受体偏好逐渐向利用人源型α2-6连接的唾液酸受体发展，随后在1995年后重新开始使用禽源型α2-3连接的受体。该筛选确定了结合与感染效率之间缺乏定量相关性，表明除附着外还存在特定的受体需求。利用该系统可对病毒-聚糖相互作用以及其他与细胞的唾液酸聚糖依赖性相互作用进行功能分析。
