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比较转录组分析揭示了 SARS-CoV-2 感染中的关键表观遗传靶标。

Comparative transcriptome analysis reveals key epigenetic targets in SARS-CoV-2 infection.

机构信息

Departamento de Ciencias Naturales, Universidad Autónoma Metropolitana-Cuajimalpa (UAM-C), Mexico City, Mexico.

Chair of Experimental Bioinformatics, TUM School of Life Sciences Weihenstephan, Technical University of Munich, Munich, Germany.

出版信息

NPJ Syst Biol Appl. 2021 May 24;7(1):21. doi: 10.1038/s41540-021-00181-x.

Abstract

COVID-19 is an infection caused by SARS-CoV-2 (Severe Acute Respiratory Syndrome coronavirus 2), which has caused a global outbreak. Current research efforts are focused on the understanding of the molecular mechanisms involved in SARS-CoV-2 infection in order to propose drug-based therapeutic options. Transcriptional changes due to epigenetic regulation are key host cell responses to viral infection and have been studied in SARS-CoV and MERS-CoV; however, such changes are not fully described for SARS-CoV-2. In this study, we analyzed multiple transcriptomes obtained from cell lines infected with MERS-CoV, SARS-CoV, and SARS-CoV-2, and from COVID-19 patient-derived samples. Using integrative analyses of gene co-expression networks and de-novo pathway enrichment, we characterize different gene modules and protein pathways enriched with Transcription Factors or Epifactors relevant for SARS-CoV-2 infection. We identified EP300, MOV10, RELA, and TRIM25 as top candidates, and more than 60 additional proteins involved in the epigenetic response during viral infection that has therapeutic potential. Our results show that targeting the epigenetic machinery could be a feasible alternative to treat COVID-19.

摘要

COVID-19 是由 SARS-CoV-2(严重急性呼吸系统综合症冠状病毒 2)引起的感染,已在全球范围内暴发。目前的研究工作集中在了解 SARS-CoV-2 感染涉及的分子机制,以便提出基于药物的治疗选择。由于表观遗传调控导致的转录变化是宿主细胞对病毒感染的关键反应,已在 SARS-CoV 和 MERS-CoV 中进行了研究;然而,对于 SARS-CoV-2,这种变化并未得到充分描述。在这项研究中,我们分析了来自感染 MERS-CoV、SARS-CoV 和 SARS-CoV-2 的细胞系以及 COVID-19 患者来源样本的多个转录组。通过基因共表达网络和从头途径富集的综合分析,我们描述了不同的基因模块和富含与 SARS-CoV-2 感染相关的转录因子或表观因子的蛋白质途径。我们确定 EP300、MOV10、RELA 和 TRIM25 为顶级候选物,以及在病毒感染期间具有治疗潜力的 60 多种参与表观遗传反应的额外蛋白质。我们的研究结果表明,靶向表观遗传机制可能是治疗 COVID-19 的可行替代方案。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c6e1/8144203/5de6bedd24ed/41540_2021_181_Fig1_HTML.jpg

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