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Identification of an Interferon-Stimulated Long Noncoding RNA (LncRNA ISR) Involved in Regulation of Influenza A Virus Replication

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  • Identification of an Interferon-Stimulated Long Noncoding RNA (LncRNA ISR) Involved in Regulation of Influenza A Virus Replication


    Int J Mol Sci. 2019 Oct 16;20(20). pii: E5118. doi: 10.3390/ijms20205118. Identification of an Interferon-Stimulated Long Noncoding RNA (LncRNA ISR) Involved in Regulation of Influenza A Virus Replication.

    Pan Q1, Zhao Z2, Liao Y3, Chiu SH4, Wang S5, Chen B6, Chen N7, Chen Y8, Chen JL9,10.
    Author information

    1 Key Laboratory of Fujian-Taiwan Animal Pathogen Biology, College of Animal Sciences, Fujian Agriculture and Forestry University, Fuzhou 350002, China. 13665015716@163.com. 2 CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China. zhaozhong.hui@163.com. 3 Key Laboratory of Fujian-Taiwan Animal Pathogen Biology, College of Animal Sciences, Fujian Agriculture and Forestry University, Fuzhou 350002, China. liaoyuan919@163.com. 4 Key Laboratory of Fujian-Taiwan Animal Pathogen Biology, College of Animal Sciences, Fujian Agriculture and Forestry University, Fuzhou 350002, China. shchiu802@163.com. 5 Key Laboratory of Fujian-Taiwan Animal Pathogen Biology, College of Animal Sciences, Fujian Agriculture and Forestry University, Fuzhou 350002, China. wscookie@163.com. 6 CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China. chenbiaozhuifeng@163.com. 7 Key Laboratory of Fujian-Taiwan Animal Pathogen Biology, College of Animal Sciences, Fujian Agriculture and Forestry University, Fuzhou 350002, China. a747110207@163.com. 8 CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China. chenyuhai@im.ac.cn. 9 Key Laboratory of Fujian-Taiwan Animal Pathogen Biology, College of Animal Sciences, Fujian Agriculture and Forestry University, Fuzhou 350002, China. chenjl@im.ac.cn. 10 CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China. chenjl@im.ac.cn.

    Abstract

    Long noncoding RNAs (lncRNAs) are involved in a diversity of biological processes. It is known that differential expression of thousands of lncRNAs occurs in host during influenza A virus (IAV) infection. However, only few of them have been well characterized. Here, we identified a lncRNA, named as interferon (IFN)-stimulated lncRNA (ISR), which can be significantly upregulated in response to IAV infection in a mouse model. A sequence alignment revealed that lncRNA ISR is present in mice and human beings, and indeed, we found that it was expressed in several human and mouse cell lines and tissues. Silencing lncRNA ISR in A549 cells resulted in a significant increase in IAV replication, whereas ectopic expression of lncRNA ISR reduced the viral replication. Interestingly, interferon-β (IFN-β) treatment was able to induce lncRNA ISR expression, and induction of lncRNA ISR by viral infection was nearly abolished in host deficient of IFNAR1, a type I IFN receptor. Furthermore, the level of IAV-induced lncRNA ISR expression was decreased either in retinoic acid-inducible gene I (RIG-I) knockout A549 cells and mice or by nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) inhibitor treatment. Together, these data elucidate that lncRNA ISR is regulated by RIG-I-dependent signaling that governs IFN-β production during IAV infection, and has an inhibitory capacity in viral replication.


    KEYWORDS:

    Influenza A virus; innate immunity; interferon; long noncoding RNAs; viral replication

    PMID: 31623059 DOI: 10.3390/ijms20205118
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