Medical School, Kunming University of Science and Technology, Kunming, 650500, China.
Medical School, Kunming University of Science and Technology, Kunming, 650500, China.
Virol Sin. 2023 Oct;38(5):699-708. doi: 10.1016/j.virs.2023.08.001. Epub 2023 Aug 3.
Long noncoding RNAs (lncRNAs) modulate many aspects of biological and pathological processes. Recent studies have shown that host lncRNAs participate in the antiviral immune response, but functional lncRNAs in coxsackievirus B5 (CVB5) infection remain unknown. Here, we identified a novel cytoplasmic lncRNA, LINC1392, which was highly inducible in CVB5 infected RD cells in a time- and dose-dependent manner, and also can be induced by the viral RNA and IFN-β. Further investigation showed that LINC1392 promoted several important interferon-stimulated genes (ISGs) expression, including IFIT1, IFIT2, and IFITM3 by activating MDA5, thereby inhibiting the replication of CVB5 in vitro. Mechanistically, LINC1392 bound to ELAV like RNA binding protein 1 (ELAVL1) and blocked ELAVL1 interaction with MDA5. Functional study revealed that the 245-835 nt locus of LINC1392 exerted the antiviral effect and was also an important site for ELAVL1 binding. In mice, LINC1392 could inhibit CVB5 replication and alleviated the histopathological lesions of intestinal and brain tissues induced by viral infection. Our findings collectively reveal that the novel LINC1392 acts as a positive regulator in the IFN-I signaling pathway against CVB5 infection. Elucidating the underlying mechanisms on how lncRNA regulats the host innate immunity response towards CVB5 infection will lay the foundation for antiviral drug research.
长链非编码 RNA（lncRNA）调节许多生物学和病理学过程。最近的研究表明，宿主 lncRNA 参与抗病毒免疫反应，但柯萨奇病毒 B5（CVB5）感染中的功能性 lncRNA 尚不清楚。在这里，我们鉴定了一种新型细胞质 lncRNA，LINC1392，它在 CVB5 感染的 RD 细胞中呈时间和剂量依赖性高度诱导，也可以被病毒 RNA 和 IFN-β诱导。进一步的研究表明，LINC1392 通过激活 MDA5 促进几个重要的干扰素刺激基因（ISGs）的表达，包括 IFIT1、IFIT2 和 IFITM3，从而抑制 CVB5 在体外的复制。机制上，LINC1392 与 ELAV 样 RNA 结合蛋白 1（ELAVL1）结合并阻止 ELAVL1 与 MDA5 的相互作用。功能研究表明，LINC1392 的 245-835nt 位点发挥抗病毒作用，也是 ELAVL1 结合的重要位点。在小鼠中，LINC1392 可以抑制 CVB5 复制，并减轻病毒感染引起的肠道和脑组织的组织病理学损伤。我们的研究结果表明，新型 LINC1392 作为 IFN-I 信号通路的正调节剂，对抗 CVB5 感染。阐明 lncRNA 如何调节宿主固有免疫反应对抗 CVB5 感染的潜在机制将为抗病毒药物研究奠定基础。
