Attenuation of equine influenza viruses through truncations of the NS1 protein
Attenuation of equine influenza viruses through truncations of the NS1 protein
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DOI：
10.1128/jvi.79.13.8431-8439.2005
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发表时间：
2005-07-01
影响因子：
5.4
通讯作者：
Palese, P
中科院分区：
文献类型：
--
作者：
Quinlivan, M;Zamarin, D;Palese, P
马流感是马的一种常见疾病，在世界范围内引起重大发病率。本文描述了一种基于质粒的马流感病毒反向遗传系统的建立。利用该系统，我们生成了三个编码羧基末端截断的NS1蛋白的突变病毒。我们之前已经证明，缺乏NS1基因（deINS1）的重组人流感病毒只能在干扰素（IFN）无效的系统中复制，这表明NS1蛋白负责干扰素拮抗剂活性。与先前对人类流感病毒的研究结果相反，我们发现在马流感病毒的情况下，NS1蛋白的长度与病毒的衰减水平无关。在马流感病毒中，具有最短NS1蛋白的突变病毒减毒效果最差。我们推测产生的马NS1突变病毒衰减的基础与它们的NS1蛋白表达水平有关。我们的研究结果表明，重组突变病毒在体外抑制IFN产生的能力受损，并且它们在胚胎鸡蛋、MDCK细胞或小鼠体内模型中的复制效率不如亲本重组病毒。因此，这些减毒突变型NS1病毒可能有潜力作为马流感活疫苗的候选株。
Equine influenza is a common disease of the horse, causing significant morbidity worldwide. Here we describe the establishment of a plasmid-based reverse genetics system for equine influenza virus. Utilizing this system, we generated three mutant viruses encoding carboxy-terminally truncated NS1 proteins. We have previously shown that a recombinant human influenza virus lacking the NS1 gene (deINS1) could only replicate in interferon (IFN)-incompetent systems, suggesting that the NS1 protein is responsible for IFN antagonist activity. Contrary to previous findings with human influenza virus, we found that in the case of equine influenza virus, the length of the NS1 protein did not correlate with the level of attenuation of that virus. With equine influenza virus, the mutant virus with the shortest NS1 protein turned out to be the least attenuated. We speculate that the basis for attenuation of the equine NS1 mutant viruses generated is related to their level of NS1 protein expression. Our findings show that the recombinant mutant viruses are impaired in their ability to inhibit IFN production in vitro and they do not replicate as efficiently as the parental recombinant strain in embryonated hen eggs, in MDCK cells, or in vivo in a mouse model. Therefore, these attenuated mutant NS1 viruses may have potential as candidates for a live equine influenza vaccine.