Consistent and High-Frequency Identification of an Intra-Sample Genetic Variant of SARS-CoV-2 with Elevated Fusogenic Properties [article]

Lynda Rocheleau, Geneviève Laroche, Kathy Fu, Marceline Côté, Patrick M Giguère, Marc-André Langlois, Martin Pelchat
2020 bioRxiv   pre-print
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has a genome comprised of a ~30K nucleotides non-segmented, positive single-stranded RNA. Although its RNA-dependent RNA polymerase exhibits exonuclease proofreading activity, viral sequence diversity can be induced by replication errors and host factors. These variations can be observed in the population of viral sequences isolated from infected host cells and are not necessarily reflected in the genome of transmitted founder
more » ... smitted founder viruses. We profiled intra-sample genetic diversity of SARS-CoV-2 variants using 15,289 high-throughput sequencing datasets from infected individuals and infected cell lines. Most of the genetic variations observed, including C->U and G->U, were consistent with errors due to heat-induced DNA damage during sample processing, and/or sequencing protocols. Despite high mutational background, we confidently identified intra-variable positions recurrent in the samples analyzed, including several positions at the end of the gene encoding the viral S protein. Notably, most of the samples possesses a C->A missense mutation resulting in the S protein lacking the last 20 amino acids (SΔ20). Here we demonstrate that SΔ20 exhibits increased cell-to-cell fusion and syncytia formations. Our findings are suggestive of the consistent emergence of high-frequency viral quasispecies that are not horizontally transmitted but involved in intra-host infection and spread.
doi:10.1101/2020.12.03.409714 fatcat:itothuoph5gorffeyuv5bklswq