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
Affiliations
Małgorzata Kurkowiak
International Centre for Cancer Vaccine Science, University of Gdańsk, Gdańsk, Poland; Corresponding author
Sarah Fletcher
The Roslin Institute, Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush, Midlothian, UK
Alison Daniels
The Roslin Institute, Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush, Midlothian, UK; Infection Medicine, University of Edinburgh, Little France Crescent, UK
Paweł Mozolewski
International Centre for Cancer Vaccine Science, University of Gdańsk, Gdańsk, Poland
Domenico Alessandro Silvestris
Department of Onco-haematology, IRCCS Ospedale Pediatrico Bambino Gesù, Rome, Italy
Ewelina Król
Department of Recombinant Vaccines, Intercollegiate Faculty of Biotechnology, University of Gdansk and Medical University of Gdansk, Gdansk, Poland
Natalia Marek-Trzonkowska
International Centre for Cancer Vaccine Science, University of Gdańsk, Gdańsk, Poland; Laboratory of Immunoregulation and Cellular Therapies, Department of Family Medicine Medical University of Gdańsk, Gdańsk, Poland
Ted Hupp
International Centre for Cancer Vaccine Science, University of Gdańsk, Gdańsk, Poland; Cell Signalling Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK
Christine Tait-Burkard
The Roslin Institute, Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush, Midlothian, UK; Corresponding author
Summary: 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.
