SARS-CoV-2 genomic surveillance identifies naturally occurring truncation of ORF7a that limits immune suppression

Cell Rep. 2021 Jun 1;35(9):109197. doi: 10.1016/j.celrep.2021.109197. Epub 2021 May 14.

Abstract

Over 950,000 whole-genome sequences of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been determined for viruses isolated from around the world. These sequences are critical for understanding the spread and evolution of SARS-CoV-2. Using global phylogenomics, we show that mutations frequently occur in the C-terminal end of ORF7a. We isolate one of these mutant viruses from a patient sample and use viral challenge experiments to link this isolate (ORF7aΔ115) to a growth defect. ORF7a is implicated in immune modulation, and we show that the C-terminal truncation negates anti-immune activities of the protein, which results in elevated type I interferon response to the viral infection. Collectively, this work indicates that ORF7a mutations occur frequently, and that these changes affect viral mechanisms responsible for suppressing the immune response.

Keywords: IFN response; ORF7a; SARS-CoV-2.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • COVID-19 / immunology*
  • COVID-19 / virology*
  • Chlorocebus aethiops
  • Genome, Viral
  • HEK293 Cells
  • Humans
  • Immunity*
  • Interferon Type I / immunology
  • Mutation
  • Phylogeny
  • SARS-CoV-2 / genetics*
  • SARS-CoV-2 / pathogenicity
  • Vero Cells
  • Viral Proteins / genetics*
  • Viral Proteins / immunology*
  • Viral Regulatory and Accessory Proteins / genetics

Substances

  • Interferon Type I
  • ORF7a protein, SARS-CoV-2
  • Viral Proteins
  • Viral Regulatory and Accessory Proteins