Long noncoding RNA 1392 regulates MDA5 by interaction with ELAVL1 to inhibit coxsackievirus B5 infection

Jing Li; Jinwei Li; Peiying Teng; Fan Yang; Jihong Zhang; Bo Sun; Wei Chen

doi:10.1016/j.virs.2023.08.001

October 2023

Jing Li, Jinwei Li, Peiying Teng, Fan Yang, Jihong Zhang, Bo Sun and Wei Chen. Long noncoding RNA 1392 regulates MDA5 by interaction with ELAVL1 to inhibit coxsackievirus B5 infection[J]. Virologica Sinica, 2023, 38(5): 699-708. doi: 10.1016/j.virs.2023.08.001

Citation: Jing Li, Jinwei Li, Peiying Teng, Fan Yang, Jihong Zhang, Bo Sun, Wei Chen. Long noncoding RNA 1392 regulates MDA5 by interaction with ELAVL1 to inhibit coxsackievirus B5 infection .VIROLOGICA SINICA, 2023, 38(5) : 699-708. http://dx.doi.org/10.1016/j.virs.2023.08.001

长链非编码RNA 1392(LINC1392)通过与ELAVL1相互作用调控MDA5而抑制柯萨奇病毒B5复制

医学院, 昆明理工大学

通讯作者： 陈伟, wchen@kust.edu.cn
收稿日期： 2022-08-25
录用日期： 2023-07-21

摘要

长非编码RNAs（lncRNAs）可调节生物和病理过程的许多方面。最近的研究表明，宿主lncRNA参与抗病毒免疫反应，但在柯萨奇病毒B5（CVB5）感染后具有功能性的lncRNA仍然未知。在本研究中，我们鉴定了一种新的细胞质lncRNA(LINC1392)。LINC1392在CVB5感染的RD细胞中上调表达，并具有病毒感染时间和剂量的依赖性，同时可在病毒RNA和IFN-β诱导下表达。进一步研究表明，LINC1392通过激活MDA5，促进了包括IFIT1、IFIT2和IFITM3在内的多个重要干扰素刺激基因（ISGs）的表达，进而抑制CVB5复制。机制上，LINC1392与ELAVL1结合，阻断了ELAVL1与MDA5的相互作用。功能研究表明，LINC1392的245-835nt位点不仅发挥了抗病毒的主要作用，也是与ELAVL1结合的重要位点。在小鼠体内，LINC1392同样具有抗病毒作用，同时也改善了在病毒感染后肠道和脑组织的组织病变。我们的研究表明，LINC1392在针对CVB5感染引起的IFN-I信号通路中充当了正向调节因子。阐明宿主lncRNA调控抗病毒感染的固有免疫机制，进而为抗病毒药物研究奠定基础。
- 长链非编码RNA
- , 柯萨奇病毒B5
- , I型干扰素通路
- , MDA5
- , ELAVL1

Long noncoding RNA 1392 regulates MDA5 by interaction with ELAVL1 to inhibit coxsackievirus B5 infection

Medical School, Kunming University of Science and Technology, Kunming, 650500, China

Corresponding author: Wei Chen, wchen@kust.edu.cn
Received Date: 25 August 2022
Accepted Date: 21 July 2023

Abstract

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.

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Electronic Supplementary Material

10.1016j.virs.2023.08.001-ESM.docx