Activation of interferon regulatory factor 3 is inhibited by the influenza A virus NS1 protein
Activation of interferon regulatory factor 3 is inhibited by the influenza A virus NS1 protein
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DOI：
10.1128/jvi.74.17.7989-7996.2000
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发表时间：
2000-09-01
影响因子：
5.4
通讯作者：
García-Sastre, A
中科院分区：
文献类型：
--
作者：
Talon, J;Horvath, CM;García-Sastre, A
我们提出了一种新的机制，病毒可以抑制α / β干扰素（ifn - α / β）级联。流感病毒的双链RNA （dsRNA）结合蛋白NS1通过抑制干扰素调节因子3 （IRF-3）的激活来阻止抗病毒干扰素应答，IRF-3是ifn - α / β基因表达的关键调节因子。IRF-3的激活和ifn - β mRNA的诱导在野生型（PR8）流感病毒感染的细胞中受到抑制，而在缺乏NS1基因的等基因病毒（delNS1病毒）感染的细胞中则不受抑制。此外，NS1被证明是干扰素信号通路的一般抑制剂。野生型NS1在trans中的表达可以抑制IRF-3的激活，不仅在delNS1病毒感染的细胞中，而且在异源RNA病毒（新城堡病病毒）感染的细胞中也是如此。我们认为，dsRNA结合蛋白对IRF-3激活的抑制显著有助于甲型流感病毒的毒力，也可能对其他病毒的毒力起作用。
We present a novel mechanism by which viruses may inhibit the alpha/beta interferon (IFN-alpha/beta) cascade. The double-stranded RNA (dsRNA) binding protein NS1 of influenza virus is shown to prevent the potent antiviral interferon response by inhibiting the activation of interferon regulatory factor 3 (IRF-3), a key regulator of IFN-alpha/beta gene expression. IRF-3 activation and, as a consequence, IFN-beta mRNA induction are inhibited in wild-type (PR8) influenza virus-infected cells but not in cells infected with an isogenic virus lacking the NS1 gene (delNS1 virus). Furthermore, NS1 is shown to be a general inhibitor of the interferon signaling pathway. Inhibition of IRF-3 activation can be achieved by the expression of wild-type NS1 in trans, not only in delNS1 virus-infected cells but also in tells infected with a heterologous RNA virus (New castle disease virus). We propose that inhibition of IRF-3 activation by a dsRNA binding protein significantly contributes to the virulence of influenza A viruses and possibly to that of other viruses.