The long non-coding RNA LNC_000397 negatively regulates PRRSV replication through induction of interferon-stimulated genes

文献类型： 外文期刊

第一作者： Zhang, Jing

作者： Zhang, Jing;Gan, Lipeng;Sun, Pu;Wang, Jian;Li, Dong;Cao, Yimei;Fu, Yuanfang;Li, Pinghua;Bai, Xingwen;Li, Kun;Ma, Xueqing;Bao, Huifang;Chen, Yingli;Zhang, Jie;Liu, Zaixin;Lu, Zengjun

作者机构：

关键词： PRRSV; lncRNA; RNA-Sequencing; Interferon; Antiviral

期刊名称：VIROLOGY JOURNAL （ 影响因子：5.913； 五年影响因子：4.372 ）

ISSN：

年卷期： 2022 年 19 卷 1 期

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收录情况： SCI

摘要： Background Porcine reproductive and respiratory syndrome virus (PRRSV) is one of the most significant threats to the global swine industry. It is of great importance to understand viral-host interactions to develop novel antiviral strategies. Long non-coding RNAs (lncRNAs) have emerged as critical factors regulating host antiviral immune responses. However, lncRNAs participating in virus-host interactions during PRRSV infection remain largely unexplored. Method RNA transcripts of porcine alveolar macrophages (PAMs) infected with two different PRRSV strains, GSWW/2015 and VR2332, at 24 h post-infection were sequenced by high-throughput sequencing. Four programs namely, CNCI, CPC, PFAM, and phyloCSF, were utilized to predict the coding potential of transcripts. mRNAs co-localized or co-expressed with differentially expressed lncRNAs were considered as their targets. Fuction of lncRNAs was predicted by GO and KEGG analysis of their target mRNAs. The effect of LNC_000397 on PRRSV replication was validated by knockdown its expression using siRNA. Target genes of LNC_000397 were identified by RNA-Sequencing and validated by RT-qPCR. Result In this study, we analyzed lncRNA and mRNA expression profiles of PRRSV GSWW/2015 and VR2332 infected porcine alveolar macrophages. A total of 1,147 novel lncRNAs were characterized, and 293 lncRNAs were differentially expressed. mRNAs co-localized and co-expressed with lncRNAs were enriched in pathogen-infection-related biological processes such as Influenza A and Herpes simplex infection. Functional analysis revealed the lncRNA, LNC_000397, which was up-regulated by PRRSV infection, negatively regulated PRRSV replication. Knockdown of LNC_000397 significantly impaired expression of antiviral ISGs such as MX dynamin-like GTPase 1 (MX1), ISG15 Ubiquitin-like modifier (ISG15), and radical S-adenosyl methionine domain containing 2 (RSAD2). Conclusions LNC_000397 negatively regulated PRRSV replication by inducing interferon-stimulated genes (ISGs) expression. Our study is the first report unveiling the role of host lncRNA in regulating PRRSV replication, which might be beneficial for the development of novel antiviral therapeutics.

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