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

Małgorzata Kurkowiak, Sarah Fletcher, Alison Daniels, Paweł Mozolewski, Domenico Alessandro Silvestris, Ewelina Król, Natalia Marek-Trzonkowska, Ted Hupp, Christine Tait-Burkard

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

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.

Original languageEnglish
Article number108031
Pages (from-to)1-19
Number of pages19
JournaliScience
Volume26
Issue number11
Early online date30 Sept 2023
DOIs
Publication statusPublished - 17 Nov 2023

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