NS1蛋白氨基酸截短对2009/H1N1病毒致病性及抗干扰素能力的影响
首发时间:2012-11-29
摘要:2009年H1N1甲型流感(2009/H1N1)对人类健康和生命安全造成了严重危害,对2009/pH1N1病毒基因特性分析发现,2009/H1N1病毒的NS1基因与其他亚型病毒相比,其羧基端截短了11个氨基酸(219个氨基酸),但此种截短对病毒特性有何影响尚不清楚。本研究利用定点突变技术对2009/H1N1病毒的NS1基因进行改造,使其可以表达全长NS1基因(230个氨基酸),并通过反向遗传系统以A/WSN/1933病毒为骨架拯救出两株重排病毒WSN-NS219和WSN-NS230,其可分别表达截短NS1蛋白(219个氨基酸)和全长NS1蛋白(230个氨基酸),对该重排病毒的生物学特性进行了体内、外实验研究。结果显示,WSN-NS219病毒在MDCK细胞的繁殖能力高于WSN-NS230;WSN-NS219与WSN-NS230对小鼠的致病性没有明显区别,没有引起死亡或明显的体重减轻;在抗干扰素方面,WSN-NS219抵抗干扰素的能力强于WSN-NS230。本研究结果表明,2009/H1N1病毒的NS1基因被截短有利于病毒生长繁殖,并提高了对干扰素的抗性,这可能是该病毒所以能够在人间广泛传播的原因之一。
关键词: 2009/H1N1甲型流感 NS1蛋白 干扰素 致病性
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Truncation of C-terminal amino acids in NS1 enhances the replication and IFN-β resistance of the 2009/H1N1 virus
Abstract:2009 pandemic H1N1 influenza A (2009/H1N1) viruses cause serious damage to human and public healthy worldwide. Sequence analysis showed that compared with other subtypes influenza virus,the NS1 protein of 2009/H1N1 virus has an 11 amino acids truncation at C-terminal tail. However, the role of this truncated NS1 protein is not clear. Here, we investigated the effect of eleven C-terminal amino acids truncated in NS1 protein of H1N1 virus in vivo and in vitro trait. By using reverse genetics, two reassortant viruses WSN-NS219 and WSN-NS230, containing truncated NS1 (219 a.a.) or full length NS1 (230 a.a.) respectively, were rescued in the backbone of A/WSN/1933 virus. WSN-NS219 showed better growth property in vivo, but similarly pathogenic to mice with WSN-NS230. To understand the molecular basis for the difference in virulence, we assess the antagonism and sensitivity trait against IFN of the viruses. WSN-NS219 showed stronger IFN resistance capacity than WSN-NS230. Our results suggested 11-animo-acid truncation of NS1 can enhance replication of the reassortant virus.
Keywords: 2009/H1N1 NS1 protein interferon pathogenicity
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