Department of Respiratory Medicine, The First People's Hospital of Yunnan province, Kunming, China.
The Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan, China.
PLoS One. 2020 Nov 6;15(11):e0241174. doi: 10.1371/journal.pone.0241174. eCollection 2020.
Coxsackievirus A16 (CV-A16) is one of the viruses that is most frequently associated with hand-foot-and-mouth disease (HFMD). Previous studies have shown that CV-A16 infections are mostly self-limiting, but in recent years, it has been gradually found that CV-A16 infections can also induce neurological complications and eventually cause death in children with HFMD. Moreover, no curative drugs or preventative vaccines have been developed for CV-A16 infection. Therefore, it is particularly important to investigate the mechanism of CV-A16 infection-induced neuropathy. In the current study, transcriptome sequencing technology was used to identify changes in the transcriptome of SH-SY5Y cells infected with CV-A16, which might hide the mechanism of CV-A16-induced neuropathology. The transcriptome profiling showed that 82,406,974, 108,652,260 and 97,753,565 clean reads were obtained in the Control, CV-A16-12 h and CV-A16-24 h groups, respectively. And it was further detected that a total of 136 and 161 differentially expressed genes in CV-A16-12 h and CV-A16-24 h groups, respectively, when compared with Control group. Then, to explore the mechanism of CV-A16 infection, we focused on the common differentially expressed genes at different time points of CV-A16 infection and found that there were 34 differentially expressed genes based on which clustering analysis and functional category enrichment analysis were performed. The results indicated that changes in oxidation levels were particularly evident in the GO term analysis, while only the "Gonadotropin-releasing hormone receptor pathway" was enriched in the KEGG pathway analysis, which might be closely related to the neurotoxicity caused by CV-A16 infection. Meanwhile, the ID2 closely related to nervous system has been demonstrated to be increased during CV-A16 infection. Additionally, the data on differentially expressed non-protein-coding genes of different types within the transcriptome sequencing results were analyzed, and it was speculated that these dysregulated non-protein-coding genes played a pivotal role in CV-A16 infection. Ultimately, qRT-PCR was utilized to validate the transcriptome sequencing findings, and the results of qRT-PCR were in agreement with the transcriptome sequencing data. In conclusion, transcriptome profiling was carried out to analyze response of SH-SY5Y cells to CV-A16 infection. And our findings provide important information to elucidate the possible molecular mechanisms which were linked to the neuropathogenesis of CV-A16 infection.
柯萨奇病毒 A16（CV-A16）是与手足口病（HFMD）最相关的病毒之一。先前的研究表明，CV-A16 感染大多是自限性的，但近年来逐渐发现，CV-A16 感染也可引起神经并发症，并最终导致 HFMD 患儿死亡。此外，尚无针对 CV-A16 感染的治疗药物或预防疫苗。因此，研究 CV-A16 感染诱导的神经病的发病机制尤为重要。在本研究中，我们使用转录组测序技术鉴定了感染 CV-A16 的 SH-SY5Y 细胞的转录组变化，这些变化可能隐藏了 CV-A16 诱导神经病理学的机制。转录组谱分析显示，对照组、CV-A16-12 h 组和 CV-A16-24 h 组分别获得了 82,406,974、108,652,260 和 97,753,565 条清洁读段。进一步检测发现，与对照组相比，CV-A16-12 h 组和 CV-A16-24 h 组分别有 136 个和 161 个差异表达基因。然后，为了探讨 CV-A16 感染的机制，我们关注了 CV-A16 感染不同时间点的共同差异表达基因，并发现基于聚类分析和功能类别富集分析，有 34 个差异表达基因。结果表明，在 GO 术语分析中氧化水平的变化尤为明显，而在 KEGG 途径分析中仅富集了“促性腺激素释放激素受体途径”，这可能与 CV-A16 感染引起的神经毒性密切相关。同时，在 CV-A16 感染过程中，与神经系统密切相关的 ID2 被证明增加。此外，对转录组测序结果中不同类型差异表达非蛋白编码基因的数据进行了分析，推测这些失调的非蛋白编码基因在 CV-A16 感染中发挥了关键作用。最后，利用 qRT-PCR 验证了转录组测序结果，qRT-PCR 的结果与转录组测序数据一致。总之，我们进行了转录组谱分析，以分析 SH-SY5Y 细胞对 CV-A16 感染的反应。我们的发现为阐明可能与 CV-A16 感染神经发病机制相关的分子机制提供了重要信息。
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