SARS-CoV-2 ORF8 accessory protein is a virulence factor

mBio. 2023 Oct 31;14(5):e0045123. doi: 10.1128/mbio.00451-23. Epub 2023 Aug 25.


The relevance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ORF8 in the pathogenesis of COVID-19 is unclear. Virus natural isolates with deletions in ORF8 were associated with wild milder disease, suggesting that ORF8 might contribute to SARS-CoV-2 virulence. This manuscript shows that ORF8 is involved in inflammation and in the activation of macrophages in two experimental systems: humanized K18-hACE2 transgenic mice and organoid-derived human airway cells. These results identify ORF8 protein as a potential target for COVID-19 therapies.

Keywords: SARS-CoV-2; accessory proteins; coronavirus; viral pathogenesis; virulence.

MeSH terms

  • Animals
  • COVID-19*
  • Humans
  • Mice
  • Mice, Transgenic
  • Respiratory System
  • SARS-CoV-2* / genetics
  • Virulence Factors / genetics


  • Virulence Factors