The sensor RIG-I detects double-stranded RNA derived from RNA viruses. Although RIG-I is also known to have a role in the antiviral response to DNA viruses, physiological RNA species recognized by RIG-I during infection with a DNA virus are largely unknown. Using next-generation RNA sequencing (RNAseq), we found that host-derived RNAs, most prominently 5S ribosomal RNA pseudogene 141 (RNA5SP141), bound to RIG-I during infection with herpes simplex virus 1 (HSV-1). Infection with HSV-1 induced relocalization of RNA5SP141 from the nucleus to the cytoplasm, and virus-induced shutoff of host protein synthesis downregulated the abundance of RNA5SP141-interacting proteins, which allowed RNA5SP141 to bind RIG-I and induce the expression of type I interferons. Silencing of RNA5SP141 strongly dampened the antiviral response to HSV-1 and the related virus 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 depletion of their respective binding proteins by the virus.

中文翻译：

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病毒对细胞5S rRNA假基因转录物的暴露可诱导RIG-I介导的免疫。

RIG-I传感器可检测源自RNA病毒的双链RNA。尽管众所周知RIG-I在对DNA病毒的抗病毒反应中也有作用，但在RIG-I感染DNA病毒的过程中被RIG-I识别的生理RNA种类还是非常未知的。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（RNA5SP141），在单纯疱疹病毒1（HSV-1）感染期间与RIG-I结合。HSV-1感染引起RNA5SP141从细胞核到细胞质的重新定位，并且病毒引起的宿主蛋白合成的关闭下调了RNA5SP141相互作用蛋白的丰度，从而使RNA5SP141结合RIG-I并诱导I型干扰素的表达。 。RNA5SP141的沉默大大减弱了对HSV-1和相关病毒爱泼斯坦-巴尔病毒（EBV）以及甲型流感病毒（IAV）的抗病毒反应。我们的发现表明，抗病毒免疫可以由宿主RNA触发，而宿主RNA会在病毒耗尽其各自的结合蛋白后被屏蔽。