病毒诱导的长链非编码 RNA-BTX 通过调节 DHX9 和 ILF3 的细胞内易位来诱导先天逃逸，从而允许病毒复制。
Virus-induced lncRNA-BTX allows viral replication by regulating intracellular translocation of DHX9 and ILF3 to induce innate escape.
机构信息
Frontier Research Center for Cell Response, Institute of Immunology, College of Life Sciences, Nankai University, Tianjin 300071, China.
Department of Immunology, Institute of Basic Medical Sciences, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100005, China.
出版信息
Cell Rep. 2023 Oct 31;42(10):113262. doi: 10.1016/j.celrep.2023.113262.
The roles of long noncoding RNA (lncRNA) and RNA-binding proteins (RBPs) in antiviral innate response warrant further investigation. Here, we identify an lncRNA, termed lncRNA-BTX (between Tbk1 and Xpot), which is upregulated upon viral infection via an IRF3-type I interferon-independent pathway, promoting viral innate immune escape. Deletion of lncRNA-BTX in cells or mice significantly reduces viral load in vitro or in vivo, respectively. Mechanistically, lncRNA-BTX strengthens the interactions between DHX9 or ILF3 (two RBPs that have opposite functions in regulating the replication of RNA virus) and their respective partner, JMJD6 or ILF2, which regulates intracellular translocations of DHX9 and ILF3 from the nucleus to the cytoplasm. Put simply, lncRNA-BTX facilitates DHX9's return to the cytoplasm and retains ILF3 within the nucleus, promoting viral replication. This work unveils a strategy developed by the virus to bypass host innate immunity, thus providing a potential target for antiviral therapeutics.
长链非编码 RNA（lncRNA）和 RNA 结合蛋白（RBPs）在抗病毒先天免疫反应中的作用值得进一步研究。在这里，我们鉴定出一种 lncRNA，称为 lncRNA-BTX（位于 TBK1 和 Xpot 之间），它通过一种 IRF3 型干扰素非依赖性途径在病毒感染时上调，促进病毒先天免疫逃逸。细胞或小鼠中 lncRNA-BTX 的缺失分别显著降低了体外或体内的病毒载量。在机制上，lncRNA-BTX 增强了 DHX9 或 ILF3（两种在调节 RNA 病毒复制方面具有相反功能的 RBPs）与其各自伴侣 JMJD6 或 ILF2 之间的相互作用，从而调节 DHX9 和 ILF3 从细胞核到细胞质的细胞内易位。简单地说，lncRNA-BTX 促进了 DHX9 回到细胞质，并使 ILF3 保留在核内，从而促进了病毒的复制。这项工作揭示了病毒逃避宿主先天免疫的一种策略，从而为抗病毒治疗提供了一个潜在的靶点。
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