Profiling host ANP32A splicing landscapes to predict influenza A virus polymerase adaptation
Profiling host ANP32A splicing landscapes to predict influenza A virus polymerase adaptation
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DOI：
10.1038/s41467-019-11388-2
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发表时间：
2019-07-30
影响因子：
16.6
通讯作者：
Hale, Benjamin G.
中科院分区：
文献类型：
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作者：
Domingues, Patricia;Eletto, Davide;Hale, Benjamin G.
细胞因素的物种差异限制了甲型禽流感病毒 (IAV) 人畜共患病和人类大流行。 IAV 聚合酶 vPol 具有克服限制并确定毒力的进化位点。在这里，我们将宿主 ANP32A 确定为选择的关键驱动因素，并确定了预测病毒进化的宿主特异性 ANP32A 剪接景观。我们发现鸟类在 vPol 促进插入中差异表达三种 ANP32A 亚型。具有较短插入片段的 ANP32A 与 vPol 相互作用较差，在支持类鸟类 IAV 复制方面受到损害，并驱动具有不同动力学的哺乳动物适应性 vPol 序列的选择。通过将选择数据与多物种 ANP32A 剪接变异分析相结合，我们开发了一个数学模型来预测可能驱动（燕子、喜鹊）或维持（鹅、天鹅）哺乳动物适应性 vPol 特征的鸟类物种。监测数据证实了喜鹊 IAV 中多种哺乳动物适应性 vPol 替代的富集，支持了这些预测。分析宿主 ANP32A 剪接可以加强对具有大流行潜力的 IAV 的监测和根除工作。
Species' differences in cellular factors limit avian influenza A virus (IAV) zoonoses and human pandemics. The IAV polymerase, vPol, harbors evolutionary sites to overcome restriction and determines virulence. Here, we establish host ANP32A as a critical driver of selection, and identify host-specific ANP32A splicing landscapes that predict viral evolution. We find that avian species differentially express three ANP32A isoforms diverging in a vPol-promoting insert. ANP32As with shorter inserts interact poorly with vPol, are compromised in supporting avian-like IAV replication, and drive selection of mammalian-adaptive vPol sequences with distinct kinetics. By integrating selection data with multi-species ANP32A splice variant profiling, we develop a mathematical model to predict avian species potentially driving (swallow, magpie) or maintaining (goose, swan) mammalian-adaptive vPol signatures. Supporting these predictions, surveillance data confirm enrichment of several mammalian-adaptive vPol substitutions in magpie IAVs. Profiling host ANP32A splicing could enhance surveillance and eradication efforts against IAVs with pandemic potential.