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

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.

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Citation

Nemudryi, Artem, Anna Nemudraia, Tanner Wiegand, Joseph Nichols, Deann T. Snyder, Jodi F. Hedges, Calvin Cicha, et al. “SARS-CoV-2 Genomic Surveillance Identifies Naturally Occurring Truncation of ORF7a That Limits Immune Suppression.” Cell Reports 35, no. 9 (June 2021): 109197. doi:10.1016/j.celrep.2021.109197.
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