Mutational induction in SARS-CoV-2 major lineages by experimental exposure to neutralising sera

Abstract

The ongoing evolution of SARS-CoV-2 and the emergence of new viral variants bearing specific escape mutations responsible for immune evasion from antibody neutralisation has required a more accurate characterisation of the immune response as one of the evolutive forces behind viral adaptation to a largely immunised human population. In this work, culturing in the presence of neutralising sera vigorously promoted mutagenesis leading to the acquisition of known escape mutations on the spike as well as new presumptive escape mutations on structural proteins whose role as target of the neutralizing antibody response might have been thus far widely neglected. From this perspective, this study, in addition to tracing the past evolution of the species back to interactions with neutralising antibody immune response, also offers a glimpse into future evolutive scenarios.

Figure 1

Schematic representation of newly acquired mutations identified in the 90-day isolates of lineage B.1 maintained in culture in the presence of poorly, moderately, and highly neutralising serum pools (P40, P160 and P1280, respectively). Known escape mutations are highlighted in bold, while other presumptive escape mutations are highlighted in italics. The “ = ” symbol indicates a synonym mutation, whereas the “fs*” symbol indicates a frameshift mutation causing the early truncation of the protein at the specified amino acidic position. From 5’ UTR to 3’ UTR (both in white): ORF1ab (yellow), S (green), ORF3a (blue), E (orange), M (light blue), ORF6 (grey), ORF7a (pink), ORF7b (lilac), ORF8 (red), N (brown) and ORF10 (lavender).

Figure 2

Schematic representation of newly acquired mutations identified in the 90-day isolates of lineage B.1.1.7, B.1.351, P.1 and B.1.525 maintained in culture in the presence of the highly neutralising serum pool (P1280). Known escape mutations are highlighted in bold, while other presumptive escape mutations are highlighted in italics. The “ = ” symbol indicates a synonym mutation, whereas the “fs*” symbol indicates a frameshift mutation causing the early truncation of the protein at the specified amino acidic position. From 5’ UTR to 3’ UTR (both in white): ORF1ab (yellow), S (green), ORF3a (blue), E (orange), M (light blue), ORF6 (grey), ORF7a (pink), ORF7b (lilac), ORF8 (red), N (brown) and ORF10 (lavender).