Rapid spread of a SARS-CoV-2 Delta variant with a frameshift deletion in ORF7a

  1. Charles S.P. Foster
  2. William D. Rawlinson

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Abstract

Australia is currently experiencing COVID-19 outbreaks from infection with SARS-CoV-2 Delta variants (B.1.617.2, AY.3). Analysis of the index case reveals a sub-consensus level of sequencing reads (∼25%) that support a 17-nucleotide deletion in ORF7a (ORF7a Δ17del ). ORF7a Δ17del induces a frameshift mutation in ORF7a, which truncates the peptide and potentially leads to reduced suppression of host restriction factor BST-2/CD317/Tetherin. Despite this, the mutation has rapidly become represented at the consensus level in subsequent cases: approximately 72% of SARS-CoV-2 genomes in the Australian outbreak possess ORF7a Δ17del , and 99.7% (1534/1538) of Delta genomes on GISAID with ORF7a Δ17del originate from the current Australian outbreak (5 August 2021). The global abundance of this mutation might be underestimated given the difficulty of variant calling software correctly calling insertion/deletions (indels), the common inability of phylogenetics software to take indels into account, and the tendency of GISAID to not release submissions that contain a frameshift mutation (unless specifically requested). Overall, the rapid increase of persistent ORF7a Δ17del variants is concerning, and suggests either a chance founder effect with a neutral mutation yet to be purged, or that the ORF7a Δ17del mutation provides a direct selective advantage.

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    Blindingnot detected.
    Power Analysisnot detected.

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  2. Version published to 10.1101/2021.08.18.21262089v1 on medRxiv