RIG-I-mediated antiviral responses to single-stranded RNA bearing 5′-phosphates

RIG-I-mediated antiviral responses to single-stranded RNA bearing 5′-phosphates
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DOI:
10.1126/science.1132998
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发表时间:
2006-11-10
期刊:
影响因子:
56.9
通讯作者:
Sousa, Caetano Reis E.
Sousa, Caetano Reis E.
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Pichlmair, Andreas;Schulz, Oliver;Sousa, Caetano Reis E.

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据信,在病毒复制过程中产生的双链RNA(DSRNA)被认为是激活由RNA解旋酶诱导的抗病毒免疫的关键触发因素诱导的基因I(RIG-I)和黑色素瘤分化 - 相关基因5(MDA5)。我们表明,流感的一种病毒感染不会产生DSRNA,并且RIG-I被5'-磷酸盐的病毒基因组单链RNA(SSRNA)激活。这是由流感蛋白非结构化蛋白1(NS1)阻止的,该蛋白1(NS1)在感染细胞中的IG-I配合物中发现。这些结果将RIG-1识别为病毒免疫逃避的SSRNA传感器和潜在的靶标,并表明其感知5'磷酸化的RNA的能力在先天免疫系统中演变为歧视自我和非自然的方法。
Double-stranded RNA ( dsRNA) produced during viral replication is believed to be the critical trigger for activation of antiviral immunity mediated by the RNA helicase enzymes retinoic acid inducible gene I (RIG-I) and melanoma differentiation - associated gene 5 (MDA5). We showed that influenza A virus infection does not generate dsRNA and that RIG-I is activated by viral genomic single-stranded RNA (ssRNA) bearing 5'-phosphates. This is blocked by the influenza protein nonstructured protein 1 (NS1), which is found in a complex with RIG-I in infected cells. These results identify RIG-I as a ssRNA sensor and potential target of viral immune evasion and suggest that its ability to sense 5'-phosphorylated RNA evolved in the innate immune system as a means of discriminating between self and nonself.