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

Abstract

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.

Genomic epidemiology of Delta SARS-CoV-2 during transition from elimination to suppression in Aotearoa New Zealand

“…Although highly variable in position and length, frameshift deletions that induce truncation of accessory protein 7a are not unique. There are numerous independent occurrences of such a mutation across both A and B lineages of SARS-CoV-2, including among VOCs [31][32][33][34][35][36][37][38] . Global genomic surveillance of SARS-CoV-2 has shown that mutations frequently occur at the downstream regions of ORF7a with such changes often leading to premature stop codons resulting in protein products with reduced functional activity.…”

SARS‐CoV‐2 intrahost evolution in immunocompromised patients in comparison with immunocompetent populations after treatment

“…It is possible that single and large deletions in accessory genes may create changes in genome organization to cause more virus fitness. [30][31][32] We detected 30 and 15 consecutive deleted amino acids in Pts 7 and 9.…”

From elimination to suppression: genomic epidemiology of a large Delta SARS-CoV-2 outbreak in Aotearoa New Zealand

“…Although highly variable in position and length, frameshift deletions that induce truncation of accessory protein 7a are not unique. There are numerous independent occurrences of such a mutation across both A and B lineages of SARS-CoV-2, including among VOCs [42][43][44][45][46][47][48][49] . Global genomic surveillance of SARS-CoV-2 has shown that mutations frequently occur at the downstream regions of ORF7a with such changes often leading to premature stop codons resulting in protein products with reduced functional activity.…”