Impact of ADAR-induced editing of minor viral RNA populations on replication and transmission of SARS-CoV-2

Figures

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  Fig. 1.. A→G mutations in minor viral populations of SARS-CoV-2. (A) Frequency of specific mutations in the SARS-CoV-2 genome. Results show the frequency of mutation, grouped by A, C, G, and U mutations, out of all mutations detected by Ion Torrent sequencing of the SARS-CoV-2 genome. The analysis was based on 98,325 changed residues that were detected from 5.04 × 109 reads in 69 patient samples. Twenty-five percent of the changed residues were A→G mutations that constituted 0.035% of all reads. The difference between the proportion of A→G mutation and any other mutation was significant (P < 0.001, χ2 test). (B) Correlation between A→G mutations in minor viral populations of SARS-CoV-2 and viral load. Results show the viral load (log10 genome copies per swab) vs. A→G mutations in percent of all reads. Dots represent samples retrieved at first visit. Data were obtained by Ion Torrent sequencing in samples that passed sequencing quality thresholds and a viral load exceeding 4.5 log10 viral genome copies per mL. Viral load was analyzed by real-time PCR. (C) Distribution of A→G mutations in the spike region. Results show the A→G mutation frequency of minor viral populations within the…

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  Fig. 2.. Prevalence of A→G mutations in SARS-CoV-2 genome residues vs. COVID-19 mortality in Europe. Consensus sequences of SARS-CoV-2 genomes from 186,616 European patients, sampled between March and December 2020, were retrieved from the GISAID database. The left y axis shows the percent of circulating genomes, and the right y axis shows the number of deaths. The blue line shows the frequency of SARS-CoV-2 genomes sampled at indicated time points (pooled weekly) that harbored at least one out of the 84 A→G mutated sites more commonly found in samples with low viral load in the previous deep sequence patient samples (SI Appendix, Table S4). The black line shows the same results by pooled 4-wk intervals. The magenta line shows A→C mutation-bearing SARS-CoV-2 genomes (weekly), and the green line shows A→U mutation-bearing genomes (weekly). The reduction of the frequency of A→G mutations between August and December was significant (P < 0.001, χ2 test). The red line shows the number of deaths caused by COVID-19 in Europe (European Centre for Disease Prevention and Control data collection https://www.ecdc.europa.eu/en/covid-19/data-collection) from March 1 to December 14, 2020), which was…