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本文引用的文献

1
The NS1 gene of H5N1 influenza viruses circumvents the host anti-viral cytokine responses.H5N1流感病毒的NS1基因规避宿主抗病毒细胞因子反应。
Virus Res. 2004 Jul;103(1-2):107-13. doi: 10.1016/j.virusres.2004.02.022.
2
Multiple lineages of antigenically and genetically diverse influenza A virus co-circulate in the United States swine population.多种抗原性和基因不同的甲型流感病毒谱系在美国猪群中共同传播。
Virus Res. 2004 Jul;103(1-2):67-73. doi: 10.1016/j.virusres.2004.02.015.
3
Defective RNA replication and late gene expression in temperature-sensitive influenza viruses expressing deleted forms of the NS1 protein.表达NS1蛋白缺失形式的温度敏感型流感病毒中的RNA复制缺陷和晚期基因表达
J Virol. 2004 Apr;78(8):3880-8. doi: 10.1128/jvi.78.8.3880-3888.2004.
4
Human influenza virus NS1 protein enhances viral pathogenicity and acts as an RNA silencing suppressor in plants.人类流感病毒NS1蛋白可增强病毒致病性,并在植物中作为一种RNA沉默抑制因子发挥作用。
J Gen Virol. 2004 Apr;85(Pt 4):993-999. doi: 10.1099/vir.0.19735-0.
5
The influenza A virus NS1 protein binds small interfering RNAs and suppresses RNA silencing in plants.甲型流感病毒NS1蛋白可结合小干扰RNA并抑制植物中的RNA沉默。
J Gen Virol. 2004 Apr;85(Pt 4):983-991. doi: 10.1099/vir.0.19734-0.
6
Biophysical characterization of the complex between double-stranded RNA and the N-terminal domain of the NS1 protein from influenza A virus: evidence for a novel RNA-binding mode.甲型流感病毒NS1蛋白N端结构域与双链RNA复合物的生物物理特性:一种新型RNA结合模式的证据
Biochemistry. 2004 Feb 24;43(7):1950-62. doi: 10.1021/bi030176o.
7
The influenza B virus nonstructural NS1 protein is essential for efficient viral growth and antagonizes beta interferon induction.乙型流感病毒非结构蛋白NS1对于病毒的高效生长至关重要,并可拮抗β干扰素的诱导。
J Virol. 2004 Feb;78(4):1865-72. doi: 10.1128/jvi.78.4.1865-1872.2004.
8
Interferon antagonist proteins of influenza and vaccinia viruses are suppressors of RNA silencing.流感病毒和痘苗病毒的干扰素拮抗剂蛋白是RNA沉默的抑制剂。
Proc Natl Acad Sci U S A. 2004 Feb 3;101(5):1350-5. doi: 10.1073/pnas.0308308100. Epub 2004 Jan 26.
9
PABP1 and eIF4GI associate with influenza virus NS1 protein in viral mRNA translation initiation complexes.PABP1和eIF4GI在病毒mRNA翻译起始复合物中与流感病毒NS1蛋白相关联。
J Gen Virol. 2003 Dec;84(Pt 12):3263-3274. doi: 10.1099/vir.0.19487-0.
10
A recombinant influenza A virus expressing an RNA-binding-defective NS1 protein induces high levels of beta interferon and is attenuated in mice.表达RNA结合缺陷型NS1蛋白的重组甲型流感病毒可诱导高水平的β干扰素,且在小鼠中减毒。
J Virol. 2003 Dec;77(24):13257-66. doi: 10.1128/jvi.77.24.13257-13266.2003.

猪流感病毒NS1蛋白的突变会损害抗干扰素活性并导致猪的病毒减毒。

Mutations in the NS1 protein of swine influenza virus impair anti-interferon activity and confer attenuation in pigs.

作者信息

Solórzano Alicia, Webby Richard J, Lager Kelly M, Janke Bruce H, García-Sastre Adolfo, Richt Jürgen A

机构信息

National Animal Disease Center, Ames, IA 50010, USA.

出版信息

J Virol. 2005 Jun;79(12):7535-43. doi: 10.1128/JVI.79.12.7535-7543.2005.

DOI:10.1128/JVI.79.12.7535-7543.2005
PMID:15919908
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1143661/
Abstract

It has been shown previously that the nonstructural protein NS1 of influenza virus is an alpha/beta interferon (IFN-alpha/beta) antagonist, both in vitro and in experimental animal model systems. However, evidence of this function in a natural host has not yet been obtained. Here we investigated the role of the NS1 protein in the virulence of a swine influenza virus (SIV) isolate in pigs by using reverse genetics. The virulent wild-type A/Swine/Texas/4199-2/98 (TX/98) virus and various mutants encoding carboxy-truncated NS1 proteins were rescued. Growth properties of TX/98 viruses with mutated NS1, induction of IFN in tissue culture, and virulence-attenuation in pigs were analyzed and compared to those of the recombinant wild-type TX/98 virus. Our results indicate that deletions in the NS1 protein decrease the ability of the TX/98 virus to prevent IFN-alpha/beta synthesis in pig cells. Moreover, all NS1 mutant viruses were attenuated in pigs, and this correlated with the amount of IFN-alpha/beta induced in vitro. These data suggest that the NS1 protein of SIV is a virulence factor. Due to their attenuation, NS1-mutated swine influenza viruses might have a great potential as live attenuated vaccine candidates against SIV infections of pigs.

摘要

先前研究表明,在体外实验和实验动物模型系统中,流感病毒的非结构蛋白NS1是α/β干扰素(IFN-α/β)拮抗剂。然而,尚未获得该功能在自然宿主中的证据。在此,我们通过反向遗传学研究了NS1蛋白在猪流感病毒(SIV)分离株对猪的毒力中的作用。拯救了强毒野生型A/猪/得克萨斯/4199-2/98(TX/98)病毒及各种编码羧基末端截短NS1蛋白的突变体。分析并比较了具有突变NS1的TX/98病毒的生长特性、在组织培养中IFN的诱导情况以及在猪体内的毒力减弱情况,并与重组野生型TX/98病毒进行对比。我们的结果表明,NS1蛋白缺失会降低TX/98病毒阻止猪细胞中IFN-α/β合成的能力。此外,所有NS1突变病毒在猪体内毒力均减弱,且这与体外诱导产生的IFN-α/β量相关。这些数据表明,SIV的NS1蛋白是一种毒力因子。由于其毒力减弱,NS1突变的猪流感病毒作为预防猪SIV感染的减毒活疫苗候选株可能具有巨大潜力。