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APOBEC cellular enzymes as 'court jesters' in SARS-CoV-2 evolution.
Philippe Colson1,2,3, Pierre Pontarotti4,5, Jacques Fantini6,7
1IHU Méditerranée Infection, 19-21 boulevard Jean Moulin, 13005, Marseille, France. philippe.colson@univ-amu.fr.
Virus Genes
|March 14, 2026
Summary
Human APOBEC enzymes do not act as defense against SARS-CoV-2. Their activity on viral mutations can either favor or hamper viral fitness, acting as
Area of Science:
- Virology
- Molecular Biology
- Genetics
Background:
- Human cytidine deaminases, apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like (APOBEC) enzymes, are primarily known for their roles in innate antiviral immunity.
- Previous studies indicated APOBEC signatures in a significant portion of SARS-CoV-2 mutations, including hyperfertile and neutral/weakly deleterious ones.
Purpose of the Study:
- To investigate the role of APOBEC enzyme activity in SARS-CoV-2 evolution by analyzing mutation signatures.
- To determine the proportion of 'lethal' mutations in SARS-CoV-2 quasispecies with APOBEC signatures.
Main Methods:
- Analysis of SARS-CoV-2 genomes to identify mutations.
- Categorization of mutations as 'hyperfertile', 'fertile', 'neutral/weakly deleterious', and 'lethal' (detected in quasispecies but not consensus).
- Assessment of APOBEC signatures within these mutation categories.
Main Results:
- APOBEC signatures were found in nearly half of hyperfertile/fertile mutations and 23% of neutral/weakly deleterious mutations.
- A significant 29% of 'lethal' mutations, identified in quasispecies but absent in consensus genomes, exhibited APOBEC signatures.
- These findings challenge the notion of APOBEC as a solely antiviral defense mechanism against SARS-CoV-2.
Conclusions:
- Human APOBEC enzymes do not appear to function as direct defense agents against SARS-CoV-2.
- APOBEC activity on SARS-CoV-2 mutations can be context-dependent, potentially favoring or hindering viral fitness.
- The study suggests APOBEC enzymes act as 'Court Jesters' in viral evolution, influencing fitness unpredictably according to neutral evolution theories.
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