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揭示感染猪繁殖与呼吸综合征病毒的猪肺泡巨噬细胞中的长非编码 RNA 图谱。

Unveiling the long non-coding RNA profile of porcine reproductive and respiratory syndrome virus-infected porcine alveolar macrophages.

机构信息

State Key Laboratory of Veterinary Biotechnology, Heilongjiang Provincial Key Laboratory of Laboratory Animal and Comparative Medicine, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, China.

出版信息

BMC Genomics. 2021 Mar 12;22(1):177. doi: 10.1186/s12864-021-07482-9.

Abstract

BACKGROUND

Long noncoding RNA (lncRNA) is highly associated with inflammatory response and virus-induced interferon production. By far the majority of studies have focused on the immune-related lncRNAs of mice and humans, but the function of lncRNAs in porcine immune cells are poorly understood. Porcine reproductive and respiratory syndrome virus (PRRSV) impairs local immune responses in the lungs of nursery and growing pigs, whereas the virus triggers the inflammatory responses. Porcine alveolar macrophage (PAM) is the primary target cell of PRRSV, thus PRRSV is used as an in vitro model of inflammation. Here, we profiled lncRNA and mRNA repertories from PRRSV-infected PAMs to explore the underlying mechanism of porcine lncRNAs in regulating host immune responses.

RESULTS

In this study, a total of 350 annotated lncRNAs and 1792 novel lncRNAs in PAMs were identified through RNA-seq analysis. Among them 86 differentially expressed (DE) lncRNAs and 406 DE protein-coding mRNAs were identified upon PRRSV incubation. GO category and KEGG pathway enrichment analyses revealed that these DE lncRNAs and mRNAs were mainly involved in inflammation- and pathogen infection-induced pathways. The results of dynamic correlated expression networks between lncRNAs and their predicted target genes uncovered that numerous lncRNAs, such as XLOC-022175, XLOC-019295, and XLOC-017089, were correlated with innate immune genes. Further analysis validated that these three lncRNAs were positively correlated with their predicted target genes including CXCL2, IFI6, and CD163. This study suggests that porcine lncRNAs affect immune responses against PRRSV infection through regulating their target genes in PAMs.

CONCLUSION

This study provides both transcriptomic and epigenetic status of porcine macrophages. In response to PRRSV infection, comprehensive DE lncRNAs and mRNAs were profiled from PAMs. Co-expression analysis demonstrated that lncRNAs are emerging as the important modulators of immune gene activities through their critical influence upon PRRSV infection in porcine macrophages.

摘要

背景

长非编码 RNA(lncRNA)与炎症反应和病毒诱导的干扰素产生高度相关。到目前为止,大多数研究都集中在小鼠和人类的免疫相关 lncRNA 上,但猪免疫细胞中的 lncRNA 功能知之甚少。猪繁殖与呼吸综合征病毒(PRRSV)损害了仔猪和生长猪肺部的局部免疫反应,而该病毒引发了炎症反应。猪肺泡巨噬细胞(PAM)是 PRRSV 的主要靶细胞,因此 PRRSV 被用作炎症的体外模型。在这里,我们对感染 PRRSV 的 PAM 中的 lncRNA 和 mRNA 谱进行了分析,以探索猪 lncRNA 调节宿主免疫反应的潜在机制。

结果

在这项研究中,通过 RNA-seq 分析总共鉴定了 PAM 中的 350 个注释 lncRNA 和 1792 个新的 lncRNA。其中,在 PRRSV 孵育后,鉴定了 86 个差异表达(DE)lncRNA 和 406 个差异表达蛋白编码 mRNA。GO 类别和 KEGG 途径富集分析表明,这些 DE lncRNA 和 mRNA 主要参与了炎症和病原体感染诱导的途径。lncRNA 与其预测靶基因之间动态相关表达网络的结果表明,许多 lncRNA,如 XLOC-022175、XLOC-019295 和 XLOC-017089,与先天免疫基因相关。进一步的分析验证了这三个 lncRNA 与它们预测的靶基因,包括 CXCL2、IFI6 和 CD163,呈正相关。本研究表明,猪 lncRNA 通过调节其在 PAM 中的靶基因,影响对 PRRSV 感染的免疫反应。

结论

本研究提供了猪巨噬细胞的转录组和表观遗传状态。在 PRRSV 感染时,从 PAM 中对全面的 DE lncRNA 和 mRNA 进行了分析。共表达分析表明,lncRNA 通过对猪巨噬细胞中 PRRSV 感染的关键影响,正在成为免疫基因活性的重要调节因子。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd5a/7953715/3be242724aaf/12864_2021_7482_Fig1_HTML.jpg

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