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. 2023 Jun 19;46(2):e20230005.
doi: 10.1590/1678-4685-GMB-2023-0005. eCollection 2023.

The SARS-CoV-2 mutation landscape is shaped before replication starts

Diego Masone  1   2 , Maria Soledad Alvarez  3 , Luis Mariano Polo  1
Affiliations

The SARS-CoV-2 mutation landscape is shaped before replication starts

Diego Masone et al. Genet Mol Biol. .

Abstract

Mutation landscapes and signatures have been thoroughly studied in SARS-CoV-2. Here, we analyse those patterns and link their changes to the viral replication tissue in the respiratory tract. Surprisingly, a substantial difference in those patterns is observed in samples from vaccinated patients. Hence, we propose a model to explain where those mutations could originate during the replication cycle.

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Conflict of interest statement

Conflict of Interest: The authors have no competing interests to declare.

Figures

Figure 1 -
Figure 1 -. The environment of infected cells alters the G>U substitution incidence in SARS-CoV-2. (A) Analysis on SBS proportions across alpha and delta variants from unvaccinated (samples collected worldwide before 15th of January 2021, when less than 0.5% of the world population was vaccinated) and vaccinated patients. (B) Diagrammatic representation of standard (Watson and Crick) pairing of guanine and cytosine (top panel) and Hoogsteen base pairing between 8-oxoguanine and adenine (bottom panel). (C) Comparison of SBS spectra of different variants from vaccinated patients. Error bars denote confidence intervals (CI). (D) Proportion of G>U and C>A within the variants, coloured as in (C). The dotted line denotes no asymmetry (ratio=1).
Figure 2 -
Figure 2 -. The influence of compartmentalisation on SBS patterns generated by oxidation. Differential pattern caused by mutagen exposure of vRNA guanines inside (A) or outside (B) double-membrane vesicles (DMVs), where vRNA replicates. Nucleotides circled in orange denote mutations that will occur in that scenario, while those in black mark the final product of the process. DMVs are delimited by double green lines. G* indicates 8-oxoguanine. (C) Proportion of C>U/G>A and G>C/C>G within the variants, coloured as in Figure 1C.
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