Consecutive deletions in a unique Uruguayan SARS-CoV-2 lineage evidence the genetic variability potential of accessory genes.

Yanina Panzera ,Viviana Ramas ,Cristina Mogdasy ,Sandra Frabasile ,Lucía Calleros ,Natalia Goñi ,Leticia Cóppola ,Emma Condon ,Gonzalo Tomás ,Adriana Delfraro ,Natália Ramos ,Claudia Techera ,Cecilia Sorhouet ,Héctor Chiparelli ,Ana Marandino ,Maria-Noel Cortinas ,Juan Arbiza ,Sofía Grecco ,Ruben Pérez

doi:10.1371/journal.pone.0263563

Yanina Panzera , Viviana Ramas + Show 17 more

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Deletions frequently occur in the six accessory genes of SARS-CoV-2, but most genomes with deletions are sporadic and have limited spreading capability. Here, we analyze deletions in the ORF7a of the N.7 lineage, a unique Uruguayan clade from the Brazilian B.1.1.33 lineage. Thirteen samples collected during the early SARS-CoV-2 wave in Uruguay had deletions in the ORF7a. Complete genomes were obtained by Illumina next-generation sequencing, and deletions were confirmed by Sanger sequencing and capillary electrophoresis. The N.7 lineage includes several individuals with a 12-nucleotide deletion that removes four amino acids of the ORF7a. Notably, four individuals underwent an additional 68-nucleotide novel deletion that locates 44 nucleotides downstream in the terminal region of the same ORF7a. The simultaneous occurrence of the 12 and 68-nucleotide deletions fuses the ORF7a and ORF7b, two contiguous accessory genes that encode transmembrane proteins with immune-modulation activity. The fused ORF retains the signal peptide and the complete Ig-like fold of the 7a protein and the transmembrane domain of the 7b protein, suggesting that the fused protein plays similar functions to original proteins in a single format. Our findings evidence the remarkable dynamics of SARS-CoV-2 and the possibility that single and consecutive deletions occur in accessory genes and promote changes in the genomic organization that help the virus explore genetic variations and select for new, higher fit changes.

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Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a novel Betacoronavirus of the subgenus Sarbecovirus and the causative agent of the pandemic coronavirus disease 2019 (COVID-19) [1].The SARS-CoV-2 genome is a ~ 30 kb long, single-stranded, positive RNA molecule, with the typical gene organization of coronaviruses
Our findings evidence the remarkable variation dynamics of SARS-CoV-2 and the possibility that consecutive deletions occur in accessory genes to promote changes in genomic organization and structure
The results of Sanger sequencing evidenced that these smaller amplicons had two deletions, the previous Δ12 and a novel 68-nucleotide deletion (Δ68), located 44 nucleotides downstream in the ORF7a

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Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a novel Betacoronavirus of the subgenus Sarbecovirus and the causative agent of the pandemic coronavirus disease 2019 (COVID-19) [1].The SARS-CoV-2 genome is a ~ 30 kb long, single-stranded, positive RNA molecule, with the typical gene organization of coronaviruses. Accessory proteins are dispensable for replication in cell culture but may have regulatory roles during the viral cycle and contribute to the virus fitness by increasing the ability to evade the host’s innate immune response [2,3]. SARS-CoV-2 has accumulated many variations since its emergence in late 2019, including some mutations in the viral spike (S) protein that underwent rapid growth and spread. These S changes have generated concern and interest, the D614G, N501Y, E484K, and K417N amino acid replacements that have occurred in the receptor-binding domain [5]

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