Cellular Biology Section, Laboratory of Viral Diseases, NIAID, Bethesda, Maryland, United States of America.
Center for Drug Evaluation and Research, FDA, Silver Spring, Maryland, United States of America.
PLoS Pathog. 2018 Jan 18;14(1):e1006796. doi: 10.1371/journal.ppat.1006796. eCollection 2018 Jan.
Rapid antigenic evolution enables the persistence of seasonal influenza A and B viruses in human populations despite widespread herd immunity. Understanding viral mechanisms that enable antigenic evolution is critical for designing durable vaccines and therapeutics. Here, we utilize the primerID method of error-correcting viral population sequencing to reveal an unexpected role for hemagglutinin (HA) glycosylation in compensating for fitness defects resulting from escape from anti-HA neutralizing antibodies. Antibody-free propagation following antigenic escape rapidly selected viruses with mutations that modulated receptor binding avidity through the addition of N-linked glycans to the HA globular domain. These findings expand our understanding of the viral mechanisms that maintain fitness during antigenic evolution to include glycan addition, and highlight the immense power of high-definition virus population sequencing to reveal novel viral adaptive mechanisms.
尽管人群中存在广泛的群体免疫，但快速抗原进化使季节性甲型和乙型流感病毒得以持续存在。了解使抗原进化成为可能的病毒机制对于设计持久的疫苗和疗法至关重要。在这里，我们利用纠错病毒群体测序的引物 ID 方法来揭示血凝素（HA）糖基化在补偿逃避抗 HA 中和抗体的适应性缺陷方面的意外作用。抗原逃逸后的无抗体繁殖迅速选择了通过向 HA 球形结构域添加 N 连接聚糖来调节受体结合亲和力的突变病毒。这些发现扩展了我们对维持抗原进化过程中适应性的病毒机制的理解，包括糖基化，并强调了高清晰度病毒群体测序揭示新的病毒适应机制的巨大力量。
