Virus-specific editing identification approach reveals the landscape of A-to-I editing and its impacts on SARS-CoV-2 characteristics and evolution

Abstract Upon SARS-CoV-2 infection, viral intermediates specifically activate the IFN response through MDA5-mediated sensing and accordingly induce ADAR1 p150 expression, which might lead to viral A-to-I RNA editing. Here, we developed an RNA virus-specific editing identification pipeline, surveyed...

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Published in:	Nucleic acids research 2022-03, Vol.50 (5), p.2509-2521
Main Authors:	Song, Yulong, He, Xiuju, Yang, Wenbing, Wu, Yaoxing, Cui, Jun, Tang, Tian, Zhang, Rui
Format:	Article
Language:	eng
Subjects:	Adenosine Deaminase - genetics Adenosine Deaminase - immunology Adenosine Deaminase - metabolism Angiotensin-Converting Enzyme 2 - genetics Angiotensin-Converting Enzyme 2 - immunology Angiotensin-Converting Enzyme 2 - metabolism Base Sequence Binding Sites - genetics COVID-19 - genetics COVID-19 - immunology COVID-19 - virology Data Resources and Analyses Evolution, Molecular Gene Expression - immunology Humans Immunity, Innate - genetics Immunity, Innate - immunology Interferon-Induced Helicase, IFIH1 - genetics Interferon-Induced Helicase, IFIH1 - immunology Interferon-Induced Helicase, IFIH1 - metabolism Mutation Protein Binding RNA Editing - genetics RNA Editing - immunology RNA-Binding Proteins - genetics RNA-Binding Proteins - immunology RNA-Binding Proteins - metabolism SARS-CoV-2 - genetics SARS-CoV-2 - immunology SARS-CoV-2 - physiology Sequence Homology, Nucleic Acid Spike Glycoprotein, Coronavirus - genetics Spike Glycoprotein, Coronavirus - immunology Spike Glycoprotein, Coronavirus - metabolism
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Summary:	Abstract Upon SARS-CoV-2 infection, viral intermediates specifically activate the IFN response through MDA5-mediated sensing and accordingly induce ADAR1 p150 expression, which might lead to viral A-to-I RNA editing. Here, we developed an RNA virus-specific editing identification pipeline, surveyed 7622 RNA-seq data from diverse types of samples infected with SARS-CoV-2, and constructed an atlas of A-to-I RNA editing sites in SARS-CoV-2. We found that A-to-I editing was dynamically regulated, varied between tissue and cell types, and was correlated with the intensity of innate immune response. On average, 91 editing events were deposited at viral dsRNA intermediates per sample. Moreover, editing hotspots were observed, including recoding sites in the spike gene that affect viral infectivity and antigenicity. Finally, we provided evidence that RNA editing accelerated SARS-CoV-2 evolution in humans during the epidemic. Our study highlights the ability of SARS-CoV-2 to hijack components of the host antiviral machinery to edit its genome and fuel its evolution, and also provides a framework and resource for studying viral RNA editing.
ISSN:	0305-1048 1362-4962