Influenza A virus hemagglutinin glycosylation compensates for antibody escape fitness costs.
Influenza A virus hemagglutinin glycosylation compensates for antibody escape fitness costs.
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流感一种病毒血凝素糖基化补偿了抗体逃脱适应性成本。
DOI：
10.1371/journal.ppat.1006796
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发表时间：
2018-01
期刊：
影响因子：
6.7
通讯作者：
Yewdell JW
中科院分区：
文献类型：
--
作者：
Kosik I;Ince WL;Gentles LE;Oler AJ;Kosikova M;Angel M;Magadán JG;Xie H;Brooke CB;Yewdell JW
快速的抗原进化使季节性甲型和B型流感病毒在人群中持续存在，尽管存在广泛的群体免疫。了解能够使抗原进化的病毒机制对于设计持久的疫苗和疗法至关重要。在这里，我们利用错误校正病毒群体测序的primerID方法来揭示血凝素（HA）糖基化在补偿从抗HA中和抗体逃逸所导致的适应性缺陷中的意想不到的作用。抗原逃逸后的无抗体繁殖快速选择了具有突变的病毒，该突变通过向HA球状结构域添加N-连接聚糖来调节受体结合亲合力。这些发现扩展了我们对在抗原进化过程中保持适应性的病毒机制的理解，包括聚糖添加，并突出了高清晰度病毒群体测序在揭示新型病毒适应机制方面的巨大力量。季节性甲型流感病毒（IAV）每年仅在美国就造成数万人死亡和数百亿美元的经济损失，尽管广泛的预暴露和疫苗接种。IAV通过在称为抗原漂移的过程中不断积累免疫逃逸替代来逃避群体免疫，从而在人群中持续存在。不幸的是，促进IAV抗原漂移的具体机制仍不清楚，这使得很难设计出更有效的防逃逸疫苗。在这里，我们使用了一种高清晰度的群体测序方法来了解IAV如何在抗原漂移期间耐受免疫逃逸取代的积累而不失去适应性。我们发现，该病毒迅速获得N-连接的聚糖结构的血凝素（HA）蛋白逃脱后，从一组中和抗体。HA的糖基化减轻了免疫逃逸取代对与宿主细胞受体相互作用的有害影响。这些结果扩展了我们对促进IAV免疫逃避机制的理解，并突出了高清病毒群体测序在揭示新病毒适应机制方面的巨大力量。
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. Seasonal influenza A viruses (IAV) cause tens of thousands of deaths and tens of billions of dollars in economic costs every year in the U.S. alone, despite widespread pre-exposure and vaccination. IAV persists within the human population by evading herd immunity through the continual accumulation of immune escape substitutions in a process known as antigenic drift. Unfortunately, the specific mechanisms that facilitate IAV antigenic drift remain unclear, making it difficult to design more efficacious, escape-proof vaccines. Here, we used a high-definition population sequencing approach to understand how IAV tolerates the accumulation of immune escape substitutions during antigenic drift without losing fitness. We found that the virus rapidly acquired N-linked glycan structures on the hemagglutinin (HA) protein following escape from a panel of neutralizing antibodies. Glycosylation of HA alleviated the deleterious effects of immune escape substitutions on interactions with host cell receptors. These results expand our understanding of the mechanisms that facilitate IAV immune evasion, and highlight the immense power of high-definition virus population sequencing to reveal novel viral adaptive mechanisms.
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DOI：
10.1073/pnas.1108754108
发表时间：
2011-12-20
影响因子：
11.1
作者：
Das, Suman R.;Hensley, Scott E.;Yewdell, Jonathan W.
通讯作者：
Yewdell, Jonathan W.
影响因子：
5.4
作者：
Boni, Maciei F.;Zhou, Yang;Holmes, Edward C.
通讯作者：
Holmes, Edward C.
影响因子：
30.3
作者：
Das, Suman R.;Hensley, Scott E.;Yewdell, Jonathan W.
通讯作者：
Yewdell, Jonathan W.
影响因子：
64.5
作者：
CATON, AJ;BROWNLEE, GG;GERHARD, W
通讯作者：
GERHARD, W
影响因子：
3.3
作者：
de Visser, JAGM;Hermisson, J;Whitlock, MC
通讯作者：
Whitlock, MC