1. SARS-CoV-2 Genomic Surveillance Identifies Naturally Occurring Truncations of ORF7a that Limit Immune Suppression
- Author
-
Blake Wiedenheft, Calvin Cicha, Artem Nemudryi, Deann T. Snyder, Tanner Wiegand, Joseph Nichols, Diane Bimczok, Karl K Vanderwood, Jodi F. Hedges, Anna Nemudraia, Mark A. Jutila, and Helen H Lee
- Subjects
Genetics ,Mutation ,Immune system ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Phylogenomics ,Interferon-stimulated gene ,Mutant ,medicine ,Viral challenge ,Biology ,medicine.disease_cause ,Genome - Abstract
Over 200,000 whole genome sequences of SARS-CoV-2 have been determined for viruses isolated from around the world. These sequences have been 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 demonstrate that this mutation results in a growth defect. ORF7a has been implicated in immune modulation, and we show that the C-terminal truncation results in distinct changes in interferon stimulated gene expression. Collectively, this work indicates that ORF7a mutations occur frequently and that these changes affect viral mechanisms responsible for suppressing the immune response. Declaration of Interest: B.W. is the founder of SurGene LLC, and VIRIS Detection Systems Inc. B.W., A. Nemudryi, and A. Nemudraia are inventors on patents related to CRISPR-Cas systems and applications thereof.
- Published
- 2021