Host-Specific Restriction of Avian Influenza Virus Caused by Differential Dynamics of ANP32 Family Members
Host-Specific Restriction of Avian Influenza Virus Caused by Differential Dynamics of ANP32 Family Members
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DOI：
10.1093/infdis/jiz506
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发表时间：
2020-01-01
影响因子：
6.4
通讯作者：
Han, Jae Yong
中科院分区：
文献类型：
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作者：
Park, Young Hyun;Chungu, Kelly;Han, Jae Yong
背景资料。流感病毒必须利用宿主因素来完成其生命周期。鸟类和哺乳动物在宿主因子上的物种差异意味着禽流感病毒(AIV)在禽类宿主中复制良好，但在人类宿主中不能复制。酸性核磷蛋白32家族成员A(ANP32A)是禽流感病毒聚合酶(VPol)活性的宿主限制因子。ANP32A属于保守的ANP32家族，其在病毒复制过程中的功能尚不清楚。在这项研究中，我们以鸡ANP32A为研究对象，利用聚集的规则间隔短回文重复序列(CRISPR)/Cas9介导的基因组编辑来研究ANP32A和ANP32家族其他成员的功能作用。我们发现，只有鸡ANP32A，而不是ANP32B和ANP32E，在支持AIV的vPol活性方面起着关键作用。此外，我们还发现，人ANP32C、ANP32D和ANP32E对vPol活性有抑制作用，而人ANP32A和ANP32B则相反。鸡ANP32家族成员和人类ANP32家族成员对vPol活性的影响不同，提示鸡和人ANP32家族成员的不同功能和整体能力可能是导致AIVs vPol活性物种特异性的原因。
Background. Influenza viruses must utilize host factors to complete their lifecycle. Species-specific differences in host factors between birds and mammals mean that avian influenza viruses (AIVs) replicate well in avian hosts but not in human hosts. Acidic nuclear phosphoprotein 32 family member A (ANP32A) has been identified as the host restriction factor for the viral polymerase (vPol) activity of AIVs. The ANP32A belongs to the conserved ANP32 family, the functional roles of which during viral replication remain unclear.Methods. In this study, we targeted chicken ANP32A using clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9-mediated genome editing to examine the functional roles of ANP32A and other members of the ANP32 family.Results. We showed that chicken ANP32A only, not ANP32B and ANP32E, plays a pivotal role in supporting vPol activity of AIVs. Furthermore, we found that the human ANP32C, ANP32D, and ANP32E, have suppressive effects on vPol activity in contrast to human ANP32A and ANP32B.Conclusions. Chicken and human ANP32 family members had different effects on vPol activity, suggesting that species-specific vPol activity of AIVs could be caused by the differential functions and overall competency of ANP32 family members.