Virginia-Maryland Regional College of Veterinary Medicine, University of Maryland, 8075 Greenmead Drive, College Park, MD 20742, USA.
J Gen Virol. 2010 Aug;91(Pt 8):1996-2001. doi: 10.1099/vir.0.021766-0. Epub 2010 Apr 21.
The NS1 protein has been associated with the virulence of influenza A viruses. To evaluate the role of the NS1 protein in pathogenicity of pandemic H5N1 avian influenza and H1N1 2009 influenza viruses, recombinant Newcastle disease viruses (rNDVs) expressing NS1 proteins were generated. Expression of the NS1 proteins resulted in inhibition of host innate immune responses (beta interferon and protein kinase R production). In addition, the NS1 proteins were localized predominantly in the nucleus of virus-infected cells. Consequently, expression of the NS1 protein contributed to an increase in pathogenicity of rNDV in chickens. In particular, mutational analysis of H5N1 NS1 protein indicated that both the RNA-binding and effector domains affect virus pathogenicity synergistically. Our study also demonstrated that expression of H1N1/09 NS1 resulted in enhanced replication of rNDV in human cells, indicating that function of the NS1 proteins can be host-species-specific.
NS1 蛋白与甲型流感病毒的毒力有关。为了评估 NS1 蛋白在大流行性 H5N1 禽流感和 H1N1 2009 流感病毒致病性中的作用，生成了表达 NS1 蛋白的重组新城疫病毒（rNDV）。NS1 蛋白的表达导致宿主先天免疫反应（β干扰素和蛋白激酶 R 产生）受到抑制。此外，NS1 蛋白主要定位于病毒感染细胞的核内。因此，NS1 蛋白的表达导致 rNDV 在鸡中的致病性增加。特别是，H5N1 NS1 蛋白的突变分析表明，RNA 结合和效应结构域协同影响病毒的致病性。我们的研究还表明，H1N1/09 NS1 的表达导致 rNDV 在人细胞中的复制增强，表明 NS1 蛋白的功能可能具有宿主种特异性。
