tetano
Editor, Senior Moderator
Cell Rep
. 2021 May 14;109197.
doi: 10.1016/j.celrep.2021.109197. Online ahead of print.
SARS-CoV-2 genomic surveillance identifies naturally occurring truncation of ORF7a that limits immune suppression
Artem Nemudryi[SUP] 1 [/SUP], Anna Nemudraia[SUP] 1 [/SUP], Tanner Wiegand[SUP] 1 [/SUP], Joseph Nichols[SUP] 1 [/SUP], Deann T Snyder[SUP] 1 [/SUP], Jodi F Hedges[SUP] 1 [/SUP], Calvin Cicha[SUP] 1 [/SUP], Helen Lee[SUP] 1 [/SUP], Karl K Vanderwood[SUP] 2 [/SUP], Diane Bimczok[SUP] 1 [/SUP], Mark A Jutila[SUP] 1 [/SUP], Blake Wiedenheft[SUP] 3 [/SUP]
Affiliations
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 (ORF7a[SUP]Δ115[/SUP]) 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.
. 2021 May 14;109197.
doi: 10.1016/j.celrep.2021.109197. Online ahead of print.
SARS-CoV-2 genomic surveillance identifies naturally occurring truncation of ORF7a that limits immune suppression
Artem Nemudryi[SUP] 1 [/SUP], Anna Nemudraia[SUP] 1 [/SUP], Tanner Wiegand[SUP] 1 [/SUP], Joseph Nichols[SUP] 1 [/SUP], Deann T Snyder[SUP] 1 [/SUP], Jodi F Hedges[SUP] 1 [/SUP], Calvin Cicha[SUP] 1 [/SUP], Helen Lee[SUP] 1 [/SUP], Karl K Vanderwood[SUP] 2 [/SUP], Diane Bimczok[SUP] 1 [/SUP], Mark A Jutila[SUP] 1 [/SUP], Blake Wiedenheft[SUP] 3 [/SUP]
Affiliations
- PMID: 34043946
- DOI: 10.1016/j.celrep.2021.109197
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 (ORF7a[SUP]Δ115[/SUP]) 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.