SARS-CoV-2 genomic surveillance identifies naturally occurring truncation of ORF7a that limits immune suppression
| Autor: | Tanner Wiegand, Blake Wiedenheft, Artem Nemudryi, Calvin Cicha, Deann T. Snyder, Mark A. Jutila, Anna Nemudraia, Karl K Vanderwood, Diane Bimczok, Jodi F. Hedges, Joseph Nichols, Helen H Lee |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
viruses Mutant Genome Viral Biology medicine.disease_cause General Biochemistry Genetics and Molecular Biology 03 medical and health sciences Viral Proteins 0302 clinical medicine Immune system Immunity Interferon Phylogenomics Chlorocebus aethiops medicine Animals Humans Viral Regulatory and Accessory Proteins Vero Cells Phylogeny Mutation SARS-CoV-2 COVID-19 Virology 030104 developmental biology HEK293 Cells Interferon Type I Vero cell 030217 neurology & neurosurgery Interferon type I medicine.drug |
| Zdroj: | Cell reports. 35(9) |
| ISSN: | 2211-1247 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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