The N- and C-terminal domains of the NS1 protein of influenza B virus can independently inhibit IRF-3 and beta interferon promoter activation
The N- and C-terminal domains of the NS1 protein of influenza B virus can independently inhibit IRF-3 and beta interferon promoter activation
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DOI：
10.1128/jvi.78.21.11574-11582.2004
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发表时间：
2004-11-01
影响因子：
5.4
通讯作者：
García-Sastre, A
中科院分区：
文献类型：
--
作者：
Donelan, NR;Dauber, B;García-Sastre, A
甲型和乙型流感病毒的NS1蛋白(A/NS1和B/NS1蛋白)只有20%的氨基酸序列相似性。然而，这些蛋白质表现出几个功能相似之处，例如它们能够与相同的RNA靶标结合，并在体外抑制蛋白激酶R的激活。A/NS1蛋白的一个重要功能是在病毒感染期间抑制α/β干扰素(干扰素-α/β)的合成。最近，还发现B/NS1蛋白抑制病毒感染细胞中干扰素-α/β的合成。我们现在发现，B/NS1蛋白的表达补充了A/NS1缺失的甲型流感病毒的生长。在没有其他B病毒蛋白的情况下，表达全长B/NS1蛋白(281个氨基酸)及其N-末端RNA结合区(1-93个氨基酸)或C-末端结构域(94-281个氨基酸)，可抑制IRF-3核转位和干扰素-β启动子的激活。对截短的B/NS1(1-93)蛋白的突变分析表明，RNA结合活性与干扰素-β启动子的抑制有关。此外，缺失NS1的重组B型流感病毒比野生型B型流感病毒诱导更高水平的IRF-3激活和干扰素-α/β合成。我们的结果支持这一假设，即B型流感病毒的NS1蛋白在拮抗IRF-3和干扰素诱导的抗病毒宿主对病毒感染的反应中起着重要作用。
The NS1 proteins of influenza A and B viruses (A/NS1 and B/NS1 proteins) have only similar to20% amino acid sequence identity. Nevertheless, these proteins show several functional similarities, such as their ability to bind to the same RNA targets and to inhibit the activation of protein kinase R in vitro. A critical function of the A/NS1 protein is the inhibition of synthesis of alpha/beta interferon (IFN-alpha/beta) during viral infection. Recently, it was also found that the B/NS1 protein inhibits IFN-alpha/beta synthesis in virus-infected cells. We have now found that the expression of the B/NS1 protein complements the growth of an influenza A virus with A/NS1 deleted. Expression of the full-length B/NS1 protein (281 amino acids), as well as either its N-terminal RNA-binding domain (amino acids 1 to 93) or C-terminal domain (amino acids 94 to 281), in the absence of any other influenza B virus proteins resulted in the inhibition of IRF-3 nuclear translocation and IFN-beta promoter activation. A mutational analysis of the truncated B/NS1(1-93) protein showed that RNA-binding activity correlated with IFN-beta promoter inhibition. In addition, a recombinant influenza B virus with NS1 deleted induces higher levels of IRF-3 activation, as determined by its nuclear translocation, and of IFN-alpha/beta synthesis than wild-type influenza B virus. Our results support the hypothesis that the NS1 protein of influenza B virus plays an important role in antagonizing the IRF-3- and IFN-induced antiviral host responses to virus infection.