论文标题
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
论文作者
论文摘要
Covid-19是由SARS-COV-2（严重的急性呼吸综合症冠状病毒2）引起的感染，这引起了全球爆发。当前的研究工作集中在理解SARS-COV-2感染所涉及的分子机制，以提出基于药物的治疗选择。由于表观遗传调节而引起的转录变化是对病毒感染的关键宿主细胞反应，并已在SARS-COV和MERS-COV中进行了研究。但是，对于SARS-COV-2，这种变化尚未完全描述。在这项研究中，我们分析了从感染了MERS-COV，SARS-COV和SARS-COV-2的细胞系获得的多个转录组，以及从Covid-19的患者衍生样品中获得的。使用基因共表达网络和De-Novo途径富集的综合分析，我们表征了富含转录因子或与SARS-COV-2感染相关的转录因子或表现因子的不同基因模块和蛋白质途径。我们将EP300，MOV10，RELA和TRIM25鉴定为顶级候选者，在病毒感染期间，参与具有治疗潜力的表观遗传反应的另外60多个蛋白质。我们的结果表明，靶向表观遗传机制可能是治疗Covid-19的可行替代方法。
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 have therapeutic potential. Our results show that targeting the epigenetic machinery could be a feasible alternative to treat COVID-19.
