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SARS-CoV-2 感染期间抗病毒传感器和干扰素反应途径效应物的表观遗传激活。

Epigenetic activation of antiviral sensors and effectors of interferon response pathways during SARS-CoV-2 infection.

机构信息

Independent Clinical Epigenetics Laboratory, Pomeranian Medical University in Szczecin, Szczecin, Poland.

Department of General Pathology, Pomeranian Medical University in Szczecin, Szczecin, Poland.

出版信息

Biomed Pharmacother. 2022 Sep;153:113396. doi: 10.1016/j.biopha.2022.113396. Epub 2022 Jul 11.

DOI:10.1016/j.biopha.2022.113396
PMID:
36076479
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9271528/
Abstract

Recent studies have shown that methylation changes identified in blood cells of COVID-19 patients have a potential to be used as biomarkers of SARS-CoV-2 infection outcomes. However, different studies have reported different subsets of epigenetic lesions that stratify patients according to the severity of infection symptoms, and more importantly, the significance of those epigenetic changes in the pathology of the infection is still not clear. We used methylomics and transcriptomics data from the largest so far cohort of COVID-19 patients from four geographically distant populations, to identify casual interactions of blood cells' methylome in pathology of the COVID-19 disease. We identified a subset of methylation changes that is uniformly present in all COVID-19 patients regardless of symptoms. Those changes are not present in patients suffering from upper respiratory tract infections with symptoms similar to COVID-19. Most importantly, the identified epigenetic changes affect the expression of genes involved in interferon response pathways and the expression of those genes differs between patients admitted to intensive care units and only hospitalized. In conclusion, the DNA methylation changes involved in pathophysiology of SARS-CoV-2 infection, which are specific to COVID-19 patients, can not only be utilized as biomarkers in the disease management but also present a potential treatment target.

摘要

最近的研究表明，COVID-19 患者血细胞中鉴定出的甲基化变化有可能被用作 SARS-CoV-2 感染结果的生物标志物。然而，不同的研究报告了不同的表观遗传损伤亚群，这些亚群根据感染症状的严重程度对患者进行分层，更重要的是，这些表观遗传变化在感染病理学中的意义尚不清楚。我们使用了来自四个地理位置不同的 COVID-19 患者的最大队列的甲基组学和转录组学数据，以确定血液细胞甲基组在 COVID-19 疾病病理学中的偶然相互作用。我们确定了一组在所有 COVID-19 患者中无论症状如何都普遍存在的甲基化变化。这些变化不存在于患有类似 COVID-19 症状的上呼吸道感染患者中。最重要的是，鉴定出的表观遗传变化影响了干扰素反应途径相关基因的表达，并且这些基因在入住重症监护病房和仅住院的患者之间存在差异。总之，涉及 SARS-CoV-2 感染病理生理学的 DNA 甲基化变化是 COVID-19 患者特有的，不仅可以用作疾病管理的生物标志物，而且还提供了一个潜在的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2e0/9271528/a57ec3c17ea5/gr6_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2e0/9271528/63d5a7dcec79/ga1_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2e0/9271528/2777bb560df6/gr1_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2e0/9271528/1a62e4ed1afe/gr2_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2e0/9271528/038a5914b564/gr3_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2e0/9271528/c1c740635b45/gr4_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2e0/9271528/e4b5bd1be33a/gr5_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2e0/9271528/a57ec3c17ea5/gr6_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2e0/9271528/63d5a7dcec79/ga1_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2e0/9271528/2777bb560df6/gr1_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2e0/9271528/1a62e4ed1afe/gr2_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2e0/9271528/038a5914b564/gr3_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2e0/9271528/c1c740635b45/gr4_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2e0/9271528/e4b5bd1be33a/gr5_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2e0/9271528/a57ec3c17ea5/gr6_lrg.jpg

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