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

PLoS One. 2022 Feb 17;17(2):e0263563. doi: 10.1371/journal.pone.0263563. eCollection 2022.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • COVID-19 / epidemiology
  • COVID-19 / genetics
  • COVID-19 / virology*
  • Cell Lineage*
  • Child
  • Female
  • Gene Deletion*
  • Genome, Viral*
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Male
  • Middle Aged
  • Open Reading Frames / genetics*
  • Phylogeny
  • SARS-CoV-2 / classification
  • SARS-CoV-2 / genetics*
  • SARS-CoV-2 / isolation & purification
  • Uruguay / epidemiology
  • Viral Proteins / genetics*

Substances

  • Viral Proteins

Grants and funding

This work was supported by the Facultad de Ciencias and Comisión Sectorial de Investigación Científica (CSIC) (Grant CSIC Equipamiento) Plataforma Genómica Facultad de Ciencias. Responsable YP. Fundación Manuel Pérez, UdelaR (Grant Fondo Manuel Pérez). Responsable RP, JA and CM. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.