Avian ANP32B does not support influenza A virus polymerase and influenza A virus relies exclusively on ANP32A in chicken cells

Avian ANP32B does not support influenza A virus polymerase and influenza A virus relies exclusively on ANP32A in chicken cells
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禽类 ANP32B 不支持甲型流感病毒聚合酶,而甲型流感病毒仅依赖鸡细胞中的 ANP32A

DOI:
10.1101/512012
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发表时间:
2019
期刊:
--
影响因子:
--
通讯作者:
Long J
Long J
中科院分区:
--
文献类型:
--
作者:
Long J

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甲型流感病毒(IAV)受到物种障碍的影响,以防止人畜共患病的频繁传播和大流行。这些障碍之一是禽类IAV聚合酶在人类细胞中的低活性。鸟类和哺乳动物ANP32蛋白之间的差异是这种宿主范围障碍的基础。人ANP32A和ANP32B同源物都支持人类适应的流感聚合酶的功能,但不支持需要禽ANP32A的禽类IAV聚合酶的有效活性。我们在这里表明,禽类ANP32B在进化上不同于哺乳动物ANP32B,而鸡ANP32B甚至不支持人类适应病毒的IAV聚合酶活性。因此,IAV不会在缺乏ANP32A的鸡细胞中复制。鸡ANP32B在LRR5结构域上的氨基酸差异是导致其失活的原因。将这些残基转移到鸡ANP32A后,就取消了对IAV聚合酶的支持。了解ANP32的功能将有助于制定抗病毒策略,并有助于设计抗流感病毒基因组编辑的鸡。
Influenza A viruses (IAV) are subject to species barriers that prevent frequent zoonotic transmission and pandemics. One of these barriers is the poor activity of avian IAV polymerases in human cells. Differences between avian and mammalian ANP32 proteins underlie this host range barrier. Human ANP32A and ANP32B homologues both support function of human-adapted influenza polymerase but do not support efficient activity of avian IAV polymerase which requires avian ANP32A. We show here that avian ANP32B is evolutionarily distinct from mammalian ANP32B, and that chicken ANP32B does not support IAV polymerase activity even of human-adapted viruses. Consequently, IAV does not replicate in chicken cells that lack ANP32A. Amino acid differences in LRR5 domain accounted for the inactivity of chicken ANP32B. Transfer of these residues to chicken ANP32A abolished support of IAV polymerase. Understanding ANP32 function will help develop antiviral strategies and aid the design of influenza virus resistant genome edited chickens.
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