Effect on Virulence and Pathogenicity of H5N1 Influenza A Virus through Truncations of NS1 eIF4GI Binding Domain
Effect on Virulence and Pathogenicity of H5N1 Influenza A Virus through Truncations of NS1 eIF4GI Binding Domain
复制标题
NS1 eIF4GI 结合域截断对 H5N1 甲型流感病毒毒力和致病性的影响
DOI：
10.1086/656536
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发表时间：
2010-11-01
影响因子：
6.4
通讯作者：
Jin, Meilin
中科院分区：
文献类型：
--
作者：
Zhou, Hongbo;Zhu, Jiping;Jin, Meilin
为研究NS 1 eIF 4GI结合结构域对H5 N1流感病毒毒力和致病性的影响，利用8质粒反向遗传学系统构建了5株编码eIF 4GI结合结构域截短的NS 1蛋白和亲本NS 1（NS 1-wt）的重组H5 N1病毒。结果表明，与重组野生型病毒rNS 1-wt相比，NS 1-wt中85-89位缺失和5个氨基酸缺失的重组病毒在体外和体内的复制能力均较弱，而NS 1-wt中85-94位缺失或整个eIF 4GI结合结构域缺失的重组病毒在鸡和小鼠体内的复制能力均较弱。我们还表明，eIF 4 GI结合结构域截短的突变体在体外抑制干扰素产生的能力受损，并且它们在鸡胚、Madin -达比犬肾细胞或鸡和小鼠模型中的体内复制不如亲本重组菌株有效。因此，这些减毒NS 1截短病毒可能具有很大的潜力，作为减毒活疫苗候选人针对H5 N1甲型流感病毒。
To study the effect of NS1 eIF4GI binding domain on virulence and pathogenicity of H5N1 influenza A virus, 5 recombinant H5N1 viruses encoding eIF4GI binding domain-truncated NS1 proteins and parental NS1 (NS1-wt) were generated by an 8-plasmid-based reverse genetics system. The results indicated that the recombinants with the addition of 5-amino acid and the deletion position of 85-89 in NS1-wt were attenuated in replication in vitro and in vivo, compared with the recombinant wild-type virus rNS1-wt, whereas the deletion position 85-94 or the entire eIF4GI binding domain in NS1-wt displayed a significantly attenuated phenotype in chicken and mice. We also showed that the eIF4GI binding domain-truncated mutants were impaired in their ability to inhibit interferon production in vitro, and they did not replicate as efficiently as the parental recombinant strain in embryonated hen eggs, in Madin -Darby Canine Kidney cells, or in vivo in chickens and in a mouse model. Therefore, these attenuated NS1-truncated viruses may have a great potential as live attenuated vaccine candidates against H5N1 influenza A virus.