ADAR mediated A-to-I RNA editing affects SARS-CoV-2 characteristics and fuels its evolution

Abstract

Upon SARS-CoV-2 infection, viral intermediates activate the Type I interferon (IFN) response through MDA5-mediated sensing and accordingly induce ADAR1 p150 expression, which might lead to A-to-I RNA editing of SARS-CoV-2. 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, and on average, approximately 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. Collectively, our data suggest that SARS-CoV-2 hijacks components of the host antiviral machinery to edit its genome and fuel its evolution.

Omicron: What Makes the Latest SARS-CoV-2 Variant of Concern So Concerning?

“…Adenosine deaminases acting on RNAs (ADARs) convert adenosine residues to inosines leading to changes of A to G or U to C if editing happens on the opposite strand. It has been proposed that ADAR A-to-I editing might be one of the factors driving SARS-CoV-2 evolution ( 51 ), but direct experimental proof is pending. Compared to the early reference SARS-CoV-2 strain, both types of ADAR signature changes are close to the expected ratio in the Omicron genome ( Fig.…”