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Porcine endemic diarrhea virus infection regulates long noncoding RNA expression.

ABSTRACT: Long noncoding RNAs (lncRNAs) have been implicated in various life processes. However, the lncRNA expression and potential functions in porcine endemic diarrhea virus (PEDV) infection and host defense are still poorly understood. In this study, we investigated the lncRNA expression profiles during PEDV infection in intestinal porcine epithelial cell-jejunum 2 (IPEC-J2) cell lines by next-generation sequencing and identified 6188 novel lncRNAs. The functional annotation analysis revealed that these lncRNAs might be associated with many immunity-related genes. We next selected candidate lncRNAs related to immune response pathways and further identified their differential expression in PEDV-infected IPEC-J2 cells and newborn piglets. Our results demonstrated that PEDV infection regulated lncRNA expression patterns in both the IPEC-J2 cell line and piglet ileum. These findings provide the first large-scale survey of lncRNAs associated with PEDV infection, specifically the lncRNAs responsible for the activation of the immune system within the ileum.

SUBMITTER: Chen J

PROVIDER: S-EPMC7112091 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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Porcine endemic diarrhea virus infection regulates long noncoding RNA expression.

Chen Jianing J Zhang Chenyu C Zhang Na N Liu Guangliang G

Virology 20181122

Long noncoding RNAs (lncRNAs) have been implicated in various life processes. However, the lncRNA expression and potential functions in porcine endemic diarrhea virus (PEDV) infection and host defense are still poorly understood. In this study, we investigated the lncRNA expression profiles during PEDV infection in intestinal porcine epithelial cell-jejunum 2 (IPEC-J2) cell lines by next-generation sequencing and identified 6188 novel lncRNAs. The functional annotation analysis revealed that the ...[more]

PMID: 30471453

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Project description:Long noncoding RNAs (lncRNAs) play a critical role in the regulation of many important cellular processes. However, the mechanisms by which lncRNAs regulate viral infection and host immune responses are not well understood. We sought to explore lncRNA regulation of hepatitis C virus (HCV) infection and interferon response. We performed RNA sequencing (RNAseq) in Huh7.5.1 cells with or without interferon alpha (IFN?) treatment. Clustered regularly interspaced short palindromic repeats/Cas9 guide RNA (gRNA) was used to knock out selected genes. The promoter clones were constructed, and the activity of related interferon-stimulated genes (ISGs) were detected by the secrete-pair dual luminescence assay. We constructed the full-length and four deletion mutants of an interferon-induced lncRNA RP11-288L9.4 (lncRNA-IFI6) based on predicted secondary structure. Selected gene mRNAs and their proteins, together with HCV infection, in Huh7.5.1 cells and primary human hepatocytes (PHHs) were monitored by quantitative real-time PCR (qRT-PCR) and western blot. We obtained 7,901 lncRNAs from RNAseq. A total of 1,062 host-encoded lncRNAs were significantly differentially regulated by IFN? treatment. We found that lncRNA-IFI6 gRNA significantly inhibited HCV infection compared with negative gRNA control. The expression of the antiviral ISG IFI6 was significantly increased following lncRNA-IFI6 gRNA editing compared with negative gRNA control in Japanese fulminant hepatitis 1 (JFH1)-infected Huh7.5.1 cells and PHHs. We observed that lncRNA-IFI6 regulation of HCV was independent of Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling. lncRNA-IFI6 negatively regulated IFI6 promoter function through histone modification. Overexpression of the truncated spatial domain or full-length lncRNA-IFI6 inhibited IFI6 expression and increased HCV replication. Conclusion: A lncRNA, lncRNA-IFI6, regulates antiviral innate immunity in the JFH1 HCV infection model. lncRNA-IFI6 regulates HCV infection independently of the JAK-STAT pathway. lncRNA-IFI6 exerts its regulatory function via promoter activation and histone modification of IFI6 through its spatial domain.

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Porcine endemic diarrhea virus infection regulates long noncoding RNA expression.

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Porcine endemic diarrhea virus infection regulates long noncoding RNA expression.

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