Fig 1: Infected senescent cells as a putative source for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) quasispecies variant generation. a) Schematic layout presenting the identification of apolipoprotein B mRNA-editing (APOBEC)-mediated mutations in the genome of 4 672 296 SARS-CoV-2 strains available in GISAID database. For algorithmic assessment see supplementary figure S7 and the supplementary materials and methods. b) Identification of SARS-CoV-2 mutations acquired in senescent cells in two strains (B.1.222 and B.1) isolated from two different patients, following cell-culture infection for the time periods indicated (day 1 and day 14). Yellow bars show the frequency of C→U substitutions observed in the GISAID database in the next-generation sequencing (NGS) read counts (green pileups) and red bars depict the C→U frequency of mutation observed post-infection of cells in the current study, in the genome of the two employed SARS-CoV-2 strains. These sites are ranked as highest relatively to the C→U counts as observed from the GISAID database. The genomic sequences flanking each C→U are also presented, while their coordinates are shown relative to the superimposed SARS-CoV-2 genome. NGS reads were confirmed in triplicate. c) Higher frequency of C→U substitutions within APOBEC consensus (supplementary figure S7) in the genome of isolated viral progenies obtained in Vero-E6 cells. d) Increased APOBEC3G and APOBEC3H mRNA levels in infected Vero-E6 cells. e) Increased APOBEC3G and APOBEC3H protein levels in infected Vero-E6 cells.
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