Viral unmasking of cellular 5S rRNA pseudogene transcripts induces RIG-I-mediated immunity.

Viral unmasking of cellular 5S rRNA pseudogene transcripts induces RIG-I-mediated immunity.
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DOI:
10.1038/s41590-017-0005-y
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发表时间:
2018-01
期刊:
影响因子:
30.5
通讯作者:
Gack MU
Gack MU
中科院分区:
医学1区
文献类型:
--
作者:
Chiang JJ;Sparrer KMJ;van Gent M;Lässig C;Huang T;Osterrieder N;Hopfner KP;Gack MU

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传感器视黄酸诱导基因-I(RIG-I)检测来自RNA病毒的双链RNA。虽然RIG-I也已知在对DNA病毒的抗病毒应答中发挥作用,但在DNA病毒感染期间由RIG-I识别的生理RNA种类在很大程度上是未知的。使用下一代RNA测序(RNAseq),我们发现宿主来源的RNA,最突出的是5S核糖体RNA假基因141(RNA 5SP 141),在单纯疱疹病毒1(HSV-1)感染期间与RIG-I结合。HSV-1感染诱导RNA 5SP 141从细胞核重新定位到细胞质,并且病毒诱导的宿主蛋白质合成的关闭下调RNA 5SP 141相互作用蛋白,从而允许RNA 5SP 141结合RIG-I并诱导I型干扰素。RNA 5SP 141的沉默强烈抑制了对HSV-1和相关的EB病毒(EBV)以及甲型流感病毒(IAV)的抗病毒应答。我们的研究结果表明,抗病毒免疫可以由宿主RNA触发,这些RNA在病毒耗尽其各自的结合蛋白后未被屏蔽。
The sensor retinoic acid-inducible gene-I (RIG-I) detects double-stranded RNA derived from RNA viruses. Although RIG-I is also known to play a role in the antiviral response to DNA viruses, physiological RNA species recognized by RIG-I during DNA virus infection are largely unknown. Using next-generation RNA sequencing (RNAseq), we found that host-derived RNAs, most prominently 5S ribosomal RNA pseudogene 141 (RNA5SP141), bind to RIG-I during herpes simplex virus 1 (HSV-1) infection. HSV-1 infection induced relocalization of RNA5SP141 from the nucleus to the cytoplasm, and virus-induced shutoff of host protein synthesis downregulated RNA5SP141-interacting proteins, thereby allowing RNA5SP141 to bind RIG-I and induce type I interferon. Silencing of RNA5SP141 strongly dampened the antiviral response to HSV-1 and the related Epstein-Barr virus (EBV) as well as influenza A virus (IAV). Our findings reveal that antiviral immunity can be triggered by host RNAs that are unshielded following viral depletion of their respective binding proteins.
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