Department of Agricultural Biotechnology and Research Institute of Agriculture and Life Sciences, Seoul National University, Seoul, Republic of Korea.
Avian Diseases Laboratory, College of Veterinary Medicine, Konkuk University, Seoul, Republic of Korea.
J Infect Dis. 2020 Jan 1;221(1):71-80. doi: 10.1093/infdis/jiz506.
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.
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.
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.
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.
流感病毒必须利用宿主因子才能完成其生命周期。鸟类和哺乳动物之间宿主因子的物种特异性差异意味着禽流感病毒（AIV）在禽类宿主中复制良好，但在人类宿主中却不能复制。酸性核磷蛋白 32 家族成员 A（ANP32A）已被鉴定为 AIV 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作用尚不清楚。
在这项研究中，我们使用簇状规律间隔短回文重复序列（CRISPR）/Cas9 介导的基因组编辑靶向鸡 ANP32A，以研究 ANP32A 和 ANP32 家族其他成员的功能作用。
我们表明，只有鸡 ANP32A，而不是 ANP32B 和 ANP32E，对 AIVs 的 vPol 活性起关键作用。此外，我们发现人类 ANP32C、ANP32D 和 ANP32E 对 vPol 活性具有抑制作用，而人类 ANP32A 和 ANP32B 则没有。
鸡和人类的 ANP32 家族成员对 vPol 活性的影响不同，这表明 AIVs 的种特异性 vPol 活性可能是由 ANP32 家族成员的不同功能和整体功能能力引起的。
