SARS-CoV-2 variants lacking ORF8 occurred in farmed mink and pangolin

Gene. 2021 Jun 5:784:145596. doi: 10.1016/j.gene.2021.145596. Epub 2021 Mar 23.

Abstract

The SARS-CoV-2 Variant of Concern 202012/01 (VOC-202012/01) is rapidly spreading worldwide owing to its substantial transmission advantage. The variant has changes in critical sites of the spike protein with potential biological significance. Moreover, VOC-202012/01 has a mutation that inactivates the ORF8 protein, whose absence can change the clinical features of the infection. Why VOC-202012/01 is more transmissible remains unclear, but spike mutations and ORF8 inactivation stand out by their known phenotypic effects. Here I show that variants combining relevant spike mutations and the absence of ORF8 occurred in SARS-CoV-2 and related viruses circulating in other host species. A truncated ORF8 (Q23stop) occurred in a SARS-CoV-2-related virus from a pangolin seized in China in 2017, also with several mutations in critical spike sites. Strikingly, I found that variants without ORF8 (E19stop) and with the N501T spike mutation circulated in farmed mink and humans from Denmark. Although with differences to VOC-202012/01, the identification of these variants highlights the danger of having reservoirs of SARS-CoV-2 and related viruses where more transmissible variants may occur and spill over to humans.

Keywords: COVID-19; Coronaviruses; Nonsense mutations; Transmissibility.

MeSH terms

  • Animals
  • COVID-19 / transmission
  • COVID-19 / veterinary*
  • COVID-19 / virology
  • China
  • Codon, Nonsense
  • Denmark
  • Disease Reservoirs / veterinary
  • Disease Reservoirs / virology
  • Host Specificity
  • Humans
  • Mink / virology*
  • Pangolins / virology*
  • SARS-CoV-2 / genetics*
  • SARS-CoV-2 / isolation & purification
  • Spike Glycoprotein, Coronavirus / genetics*
  • Viral Proteins / genetics*
  • Viral Proteins / metabolism

Substances

  • Codon, Nonsense
  • ORF8 protein, SARS-CoV-2
  • Spike Glycoprotein, Coronavirus
  • Viral Proteins
  • spike protein, SARS-CoV-2