Seasonal influenza viruses circulating between 1918 and 2009 harboured two prevalent genetic variations in the NS1 coding region. A glutamic acid (E)-to-lysine (K) exchange at position 196 was reported to diminish the capacity of NS1 to control interferon induction. Furthermore, alterations at position 231 determine a carboxy-terminal extension of seven amino acids from 230 to 237 residues. Sequence analyses of NS1 of the last 90 years suggest that variations at these two positions are functionally linked. To determine the impact of the two positions on viral replication in vivo, we used a mouse-adapted variant of A/Hong Kong/01/68 (maHK68) (H3N2). maHK68 encodes an NS1 of 237 amino acids with lysine at position 196. A panel of recombinant maHK68 viruses was generated encoding NS1 variants that differed at positions 196 and 231. Our analyses showed a clear effect of the K-196-to-E exchange on interferon induction and virus virulence. These effects were further modulated by the loss of the seven-amino-acid extension. We propose that the combination of NS1 E-196 with the short C-terminal variant conferred a fitness advantage that is reflected by increased virulence in vivo. Notably, this particular NS1 constellation was observed for the pandemic 1918 H1N1 virus.

中文翻译：

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使用适应小鼠的A / HK / 01/68流感病毒分析196和231号密码子中NS1进化对病毒复制和毒力的影响。

在1918年至2009年之间传播的季节性流感病毒在NS1编码区具有两个普遍的遗传变异。据报道，在位置196进行的谷氨酸（E）到赖氨酸（K）的交换减少了NS1控制干扰素诱导的能力。此外，在231位的改变确定了七个氨基酸从230至237个残基的羧基末端延伸。最近90年对NS1的序列分析表明，这两个位置的变异在功能上是相关的。确定两个位置对体内病毒复制的影响，我们使用了A / Hong Kong / 01/68（maHK68）（H3N2）的小鼠适应变体。maHK68编码一个237个氨基酸的NS1，赖氨酸位于196位。生成了一组重组maHK68病毒，编码的NS1变体在196和231位不同。我们的分析表明，K-196到E交换对干扰素诱导和病毒毒力。这些作用被七氨基酸延伸的损失进一步调节。我们建议将NS1 E-196与短C端变体的组合赋予健身优势，这可通过体内增加的毒力来体现。值得注意的是，在大流行的1918 H1N1病毒中观察到了这个特定的NS1星座。