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

Abstract

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.

Rights

https://creativecommons.org/licenses/by/4.0/

Cite as

Downloadable citations

Identifiers

DOI

https://doi.org/10.1016/j.isci.2023.108031

Repository URI

https://www.research.ed.ac.uk/en/publications/6e451bf8-e2be-4dc4-9941-5b1e0065c59f