Activation of IFN-β expression by a viral mRNA through RNase L and MDA5
Activation of IFN-β expression by a viral mRNA through RNase L and MDA5
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DOI：
10.1073/pnas.1012409108
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发表时间：
2011-02-01
影响因子：
11.1
通讯作者：
He, Biao
中科院分区：
文献类型：
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作者：
Luthra, Priya;Sun, Dengyun;He, Biao
IFN在针对病毒感染的先天免疫中起关键作用。黑色素瘤分化相关蛋白5（MDA 5），一种RNA解旋酶，是响应于某些类型的病毒感染而激活I型IFN表达的关键组分。MDA 5感知非细胞RNA并触发导致IFN产生的信号级联。合成的双链RNA是已知的MDA 5激活剂。然而，还没有报道天然单链RNA激活MDA 5。我们偶然发现了一种来自副流感病毒5型（PIV 5）的病毒mRNA，它通过MDA 5激活IFN的表达。我们提供的证据表明，信号通路包括抗病毒酶RNase L。PIV 5的LmRNA激活IFN-β的表达。我们已经将RNA定位到PIV 5的L mRNA内的430个核苷酸的区域。我们的研究结果表明，具有5 '-cap和3'-poly（A）的病毒mRNA可以通过RNase L-MDA 5途径激活IFN表达。
IFNs play a critical role in innate immunity against viral infections. Melanoma differentiation-associated protein 5 (MDA5), an RNA helicase, is a key component in activating the expression of type I IFNs in response to certain types of viral infection. MDA5 senses noncellular RNA and triggers the signaling cascade that leads to IFN production. Synthetic double-stranded RNAs are known activators of MDA5. Natural single-stranded RNAs have not been reported to activate MDA5, however. We have serendipitously identified a viral mRNA from parainfluenza virus 5 (PIV5) that activates IFN expression through MDA5. We provide evidence that the signaling pathway includes the antiviral enzyme RNase L. The L mRNA of PIV5 activated expression of IFN-beta. We have mapped the RNA to a region of 430 nucleotides within the L mRNA of PIV5. Our results indicate that a viral mRNA, with 5'-cap and 3'-poly (A), can activate IFN expression through an RNase L-MDA5 pathway.