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Abstract：
Peste des petits ruminants (PPR) is an acute, highly contagious viral disease of goats and sheep, caused by the Peste des petits ruminants virus (PPRV). Earlier studies suggest the involvement of diverse regulatory mechanisms in PPRV infection. Methylation at N6 of Adenosine called m6A is a type RNA modification that influences various physiological and pathological phenomena. As the lung tissue represents the primary target organ of PPRV, the present study explored the m6A changes and their functional significance in PPRV disease pathogenesis. m6A-seq analysis revealed 1289 m6A peaks to be significantly altered in PPRV infected lung in comparison to normal lung, out of which 975 m6A peaks were hypomethylated and 314 peaks were hypermethylated. Importantly, hypomethylated genes were enriched in Interleukin-4 and Interleukin-13 signaling and various processes associated with extracellular matrix organization. Further, of the 843 differentially m6A-containing cellular transcripts, 282 transcripts were also found to be differentially expressed. Functional analysis revealed that these 282 transcripts are significantly enriched in signaling by Interleukins, extracellular matrix organization, cytokine signaling in the immune system, signaling by receptor tyrosine kinases, and Toll-like Receptor Cascades. We also found m6A reader HNRNPC and the core component of methyltransferase complex METTL14 to be highly upregulated than the m6A readers - HNRNPA2B1 and YTHDF1 at the transcriptome level. These findings suggest that alteration in the m6A landscape following PPRV is implicated in diverse processes including Interleukin signaling.
摘要：
小反刍动物(PPR)是一种急性的，山羊和绵羊的高度传染性病毒性疾病，由小反刍动物病毒（PPRV）引起。早期研究表明PPRV感染涉及多种调节机制。称为m6A的腺苷的N6甲基化是影响各种生理和病理现象的类型RNA修饰。由于肺组织代表PPRV的主要靶器官，本研究探讨了m6A的变化及其在PPRV疾病发病机制中的功能意义。m6A-seq分析显示，与正常肺相比，PPRV感染肺的1289个m6A峰显著改变，其中975个m6A峰被低甲基化，314个峰被高甲基化。重要的是,低甲基化基因富集在白细胞介素-4和白细胞介素-13信号传导以及与细胞外基质组织相关的各种过程中。Further,843个差异含有M6A的细胞转录本，还发现282个转录物差异表达。功能分析显示，这282个转录物通过白细胞介素在信号传导中显著富集，细胞外基质组织，免疫系统中的细胞因子信号，受体酪氨酸激酶的信号，和Toll样受体级联。我们还发现m6A阅读器HNRNPC和甲基转移酶复合物METTL14的核心成分在转录组水平上比m6A阅读器HNRNPA2B1和YTHDF1高度上调。这些发现表明，PPRV后m6A景观的改变与包括白细胞介素信号传导在内的多种过程有关。
