Differential RNA editing landscapes in host cell versus the SARS-CoV-2 genome

• Published in: iScience Vol. 26; no. 11; p. 108031
• Main Authors: Kurkowiak, Małgorzata, Fletcher, Sarah, Daniels, Alison, Mozolewski, Paweł, Silvestris, Domenico Alessandro, Król, Ewelina, Marek-Trzonkowska, Natalia, Hupp, Ted, Tait-Burkard, Christine
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 17.11.2023; Elsevier
• Subjects: Evolutionary biology; Virology; Evolutionary biology; Virology
• ISSN: 2589-0042; 2589-0042
• DOI: 10.1016/j.isci.2023.108031

The SARS-CoV-2 pandemic was defined by the emergence of new variants formed through virus mutation originating from random errors not corrected by viral proofreading and/or the host antiviral response introducing mutations into the viral genome. While sequencing information hints at cellular RNA editing pathways playing a role in viral evolution, here, we use an in vitro human cell infection model to assess RNA mutation types in two SARS-CoV-2 strains representing the original and the alpha variants. The variants showed both different cellular responses and mutation patterns with alpha showing higher mutation frequency with most substitutions observed being C-U, indicating an important role for apolipoprotein B mRNA editing catalytic polypeptide-like editing. Knockdown of select APOBEC3s through RNAi increased virus production in the original virus, but not in alpha. Overall, these data suggest a deaminase-independent anti-viral function of APOBECs in SARS-CoV-2 while the C-U editing itself might function to enhance genetic diversity enabling evolutionary adaptation. [Display omitted] •RNA-modifying enzymes are upregulated upon SARS-CoV-2 infection in vitro•SARS-CoV-2 VOC Alpha shows a significant increase of C-U RNA edits•Knockdown of APOBEC3B and 3D increases virus replication of original SARS-CoV-2•Effect of APOBEC3B and 3D knockdown disappears in VOCs Alpha, Delta, and Omicron Virology; Evolutionary biology