Mammalian ANP32A and ANP32B proteins drive alternative avian influenza virus polymerase adaptations
Mammalian ANP32A and ANP32B proteins drive alternative avian influenza virus polymerase adaptations
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DOI：
10.1101/2020.09.03.282384
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发表时间：
2020-09
期刊：
影响因子：
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通讯作者：
T. Peacock;C. Sheppard;E. Staller;R. Frise;Olivia C. Swann;Daniel H. Goldhill;Jason S. Long;W. Barclay
中科院分区：
文献类型：
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作者：
T. Peacock;C. Sheppard;E. Staller;R. Frise;Olivia C. Swann;Daniel H. Goldhill;Jason S. Long;W. Barclay
作为流感聚合酶辅因子的ANP 32蛋白在鸟类和哺乳动物之间存在差异。众所周知的哺乳动物适应PB 2-E627 K使流感聚合酶能够使用哺乳动物ANP 32蛋白。然而，一些适应于马达加斯加的流感病毒并不具有这种适应性。在这里，我们表明，替代PB 2适应，Q591 R和D 701 N也允许流感聚合酶使用哺乳动物ANP 32蛋白。PB 2-E627 K强烈倾向于使用哺乳动物ANP 32 B蛋白，而D 701 N没有显示出这种偏倚。因此，PB 2-E627 K适应出现在具有强前病毒ANP 32 B蛋白的物种中，如人和小鼠，而D 701 N更常见于来自猪、狗和马的分离物中，其中ANP 32 A蛋白更强地为前病毒。在实验进化方法中，禽类病毒在人细胞中的传代驱动PB 2-E627 K的获得，但当ANP 32 B被消融时不驱动。ANP 32 B对PB 2-E627 K的强前病毒支持映射到ANP 32 B的LCAR区域。
ANP32 proteins, which act as influenza polymerase co-factors, vary between birds and mammals. The well-known mammalian adaptation, PB2-E627K, enables influenza polymerase to use mammalian ANP32 proteins. However, some mammalian-adapted influenza viruses do not harbour this adaptation. Here, we show that alternative PB2 adaptations, Q591R and D701N also allow influenza polymerase to use mammalian ANP32 proteins. PB2-E627K strongly favours use of mammalian ANP32B proteins, whereas D701N shows no such bias. Accordingly, PB2-E627K adaptation emerges in species with strong pro-viral ANP32B proteins, such as humans and mice, while D701N is more commonly seen in isolates from swine, dogs and horses where ANP32A proteins are more strongly pro-viral. In an experimental evolution approach, passage of avian viruses in human cells drives acquisition of PB2-E627K, but not when ANP32B is ablated. The strong pro-viral support of ANP32B for PB2-E627K maps to the LCAR region of ANP32B.