Evidence for host-dependent RNA editing in the transcriptome of SARS-CoV-2

Evidence for host-dependent RNA editing in the transcriptome of SARS-CoV-2
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DOI:
10.1126/sciadv.abb5813
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发表时间:
2020-06-01
期刊:
影响因子:
13.6
通讯作者:
Conticello, Silvestro G.
Conticello, Silvestro G.
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Di Giorgio, Salvatore;Martignano, Filippo;Conticello, Silvestro G.

文献摘要

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COVID-19疫情已成为全球健康风险,了解宿主对SARS-CoV-2病毒的反应将有助于抗击这种疾病。宿主脱氨酶的RNA编辑是一种对抗病毒感染的先天限制过程,但目前尚不清楚该过程是否对冠状病毒有效。在这里,我们分析了冠状病毒感染患者支气管肺泡灌洗液的RNA序列。我们鉴定了可能是RNA编辑特征的核苷酸变化:来自阿达尔脱氨酶的腺苷-肌苷变化和来自APOBEC脱氨酶的胞嘧啶-尿嘧啶变化。来自人类宿主的冠状病毒科不同毒株的基因组突变分析揭示了与转录组学数据中观察到的突变模式一致的突变模式。然而,这些数据中减少的阿达尔特征提高了ADAR在限制病毒繁殖方面可能比APOBEC更有效的可能性。因此,我们的研究结果表明,APOBECs和ADARs都参与了冠状病毒基因组编辑,这一过程可能会影响病毒和患者的命运。
The COVID-19 outbreak has become a global health risk, and understanding the response of the host to the SARS-CoV-2 virus will help to combat the disease. RNA editing by host deaminases is an innate restriction process to counter virus infection, but it is not yet known whether this process operates against coronaviruses. Here, we analyze RNA sequences from bronchoalveolar lavage fluids obtained from coronavirus-infected patients. We identify nucleotide changes that may be signatures of RNA editing: adenosine-to-inosine changes from ADAR deaminases and cytosine-to-uracil changes from APOBEC deaminases. Mutational analysis of genomes from different strains of Coronaviridae from human hosts reveals mutational patterns consistent with those observed in the transcriptomic data. However, the reduced ADAR signature in these data raises the possibility that ADARs might be more effective than APOBECs in restricting viral propagation. Our results thus suggest that both APOBECs and ADARs are involved in coronavirus genome editing, a process that may shape the fate of both virus and patient.