The PDZ-binding motif of the avian NS1 protein affects transmission of the 2009 influenza A(H1N1) virus
The PDZ-binding motif of the avian NS1 protein affects transmission of the 2009 influenza A(H1N1) virus
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DOI：
10.1016/j.bbrc.2014.04.132
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发表时间：
2014-06-20
影响因子：
3.1
通讯作者：
Park, Man-Seong
中科院分区：
文献类型：
--
作者：
Kim, Jin Il;Hwang, Min-Woong;Park, Man-Seong
由于其分段RNA基因组的性质，甲型流感病毒（IAV）具有通过重配过程产生变体的潜力。流感病毒非结构基因（NS）是病毒抵抗宿主抗病毒反应的关键基因。因此，新获得的NS片段可能决定了重组病毒在一系列不同宿主中的复制效率。此外，C-末端PDZ结合基序（PBM）已被认为是IAV的致病决定因素。为了评估人类和禽类IAV重配的大流行潜力，我们评估了NS重配病毒在培养细胞和小鼠肺中的复制特性，并确定了它们在豚鼠中的传播性。与重组A/Korea/01/2009病毒（rK 09; 2009年大流行H1N1毒株）相比，其中NS基因采用自A/Vietnam/1203/2004病毒（高致病性禽流感H5 N1病毒毒株的人分离株）的rK 09/VN：NS病毒表现出减弱的毒力和降低的传播性。然而，在NS 1蛋白的C-末端携带PBM的rK 09/VN：NS-PBM病毒恢复了rK 09/VN：NS病毒的减毒毒力。在豚鼠模型中，rK 09/VN：NS-PBM病毒显示出比rK/09病毒更高的传播效率。这些结果表明，PBM在NS 1蛋白可能决定病毒的持久性在人类和鸟类IAV接口。(C)2014爱思唯尔公司All rights reserved.
By nature of their segmented RNA genome, influenza A viruses (IAVs) have the potential to generate variants through a reassortment process. The influenza nonstructural (NS) gene is critical for a virus to counteract the antiviral responses of the host. Therefore, a newly acquired NS segment potentially determines the replication efficiency of the reassortant virus in a range of different hosts. In addition, the C-terminal PDZ-binding motif (PBM) has been suggested as a pathogenic determinant of IAVs. To gauge the pandemic potential from human and avian IAV reassortment, we assessed the replication properties of NS-reassorted viruses in cultured cells and in the lungs of mice and determined their transmissibility in guinea pigs. Compared with the recombinant A/Korea/01/2009 virus (rK09; 2009 pandemic H1N1 strain), the rK09/VN:NS virus, in which the NS gene was adopted from the A/Vietnam/1203/2004 virus (a human isolate of the highly pathogenic avian influenza H5N1 virus strains), exhibited attenuated virulence and reduced transmissibility. However, the rK09/VN:NS-PBM virus, harboring the PBM in the C-terminus of the NS1 protein, recovered the attenuated virulence of the rK09/VN:NS virus. In a guinea pig model, the rK09/VN:NS-PBM virus showed even greater transmission efficiency than the rK/09 virus. These results suggest that the PBM in the NS1 protein may determine viral persistence in the human and avian IAV interface. (C) 2014 Elsevier Inc. All rights reserved.