Journal
CELL REPORTS
Volume 33, Issue 1, Pages -Publisher
CELL PRESS
DOI: 10.1016/j.celrep.2020.108234
Keywords
-
Categories
Funding
- NIH [AI142759, AI134907, AI145617, UL1TR001439, R01AI134907, R21AI132479-01, R21AI126012-01A1, U19AI100625, R00AG049092, R24AI120942]
- Sealy & Smith Foundation
- Kleberg Foundation
- John S. Dunn Foundation
- Amon G. Carter Foundation
- Gillson Longenbaugh Foundation
- Summerfield Robert Foundation
- STARs Award from the University of Texas System
Ask authors/readers for more resources
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication and host immune response determine coronavirus disease 2019 (COVID-19), but studies evaluating viral evasion of immune response are lacking. Here, we use unbiased screening to identify SARS-CoV-2 proteins that antagonize type I interferon (IFN-I) response. We found three proteins that antagonize IFN-I production via distinct mechanisms: nonstructural protein 6 (nsp6) binds TANK binding kinase 1 (TBK1) to suppress interferon regulatory factor 3 (IRF3) phosphorylation, nsp13 binds and blocks TBK1 phosphorylation, and open reading frame 6 (ORF6) binds importin Karyopherin a 2 (KPNA2) to inhibit IRF3 nuclear translocation. We identify two sets of viral proteins that antagonize IFN-I signaling through blocking signal transducer and activator of transcription 1 (STAT1)/STAT2 phosphorylation or nuclear translocation. Remarkably, SARS-CoV-2 nsp1 and nsp6 suppress IFN-I signaling more efficiently than SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV). Thus, when treated with IFN-I, a SARS-CoV-2 replicon replicates to a higher level than chimeric replicons containing nsp1 or nsp6 from SARS-CoV or MERS-CoV. Altogether, the study provides insights on SARS-CoV-2 evasion of IFN-I response and its potential impact on viral transmission and pathogenesis.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available