Core Research Laboratory, ISPRO, Firenze 50139, Italy.
Department of Medical Biotechnologies, University of Siena, Siena 53100, Italy.
Sci Adv. 2020 Jun 17;6(25):eabb5813. doi: 10.1126/sciadv.abb5813. eCollection 2020 Jun.
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.
新型冠状病毒肺炎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对抗该疾病。宿主脱氨酶的 RNA 编辑是一种固有限制病毒感染的过程,但目前尚不清楚这一过程是否适用于冠状病毒。在这里,我们分析了来自冠状病毒感染患者支气管肺泡灌洗液中的 RNA 序列。我们鉴定了可能是 RNA 编辑特征的核苷酸变化:ADAR 脱氨酶的腺嘌呤到肌苷变化和 APOBEC 脱氨酶的胞嘧啶到尿嘧啶变化。对来自人类宿主的冠状病毒科不同株的基因组进行突变分析,揭示了与转录组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 ADAR 特征的减少提出了这样一种可能性,即 ADAR 可能比 APOBEC 更有效地限制病毒的繁殖。因此,我们的研究结果表明,APOBEC 和 ADAR 都参与了冠状病毒基因组编辑,这一过程可能决定病毒和患者的命运。