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| Status |
Public on Oct 20, 2020 |
| Title |
SARS-CoV-2 Orf6 hijacks Nup98 to block STAT nuclear import and antagonize interferon signaling |
| Organism |
Chlorocebus sabaeus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the ongoing coronavirus disease 2019 (COVID-19) pandemic that is a serious global health threat. Evasion of interferon-mediated antiviral signaling is a common defense strategy that pathogenic viruses use to replicate and propagate in their host. In this study, we show that SARS-CoV-2 is able to efficiently block STAT1 and STAT2 nuclear translocation in order to impair transcriptional induction of interferon (IFN) stimulated genes (ISGs). Our results demonstrate that the viral accessory protein Orf6 exerts this anti-IFN activity. We found that SARS-CoV-2 Orf6 localizes at the nuclear pore complex (NPC) where it directly interacts with Nup98-Rae1 via its C-terminal domain to impair docking of cargo-receptor complexes and disrupt nuclear import functions. In addition, we show that a methionine-to-arginine substitution at residue 58 impairs Orf6 binding to the Nup98-Rae1 complex and abolishes its IFN antagonistic function. All together our data unravel a new mechanism of viral antagonism in which a virus hijacks the Nup98-Rae1 complex to overcome the antiviral action of IFN.
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| Overall design |
Single cell RNA sequencing of mock and SARS-CoV-2 infected Vero E6 African green monkey cells, that were stimulated with Type I, II and III interferons
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| Contributor(s) |
Miorin L, Kehrer T, Sanchez-Aparicio MT, Garcia-Sastre A |
| Citation(s) |
33097660 |
| |
| Submission date |
Oct 19, 2020 |
| Last update date |
Dec 01, 2020 |
| Contact name |
Adolfo Garcia-Sastre |
| E-mail(s) |
Adolfo.Garcia-Sastre@mssm.edu
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| Organization name |
Icahn School of Medicine at Mount Sinai
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| Department |
Microbiology and Immunology
|
| Lab |
Adolfo Garcia-Sastre
|
| Street address |
1 Gustave Levy Pl
|
| City |
New York |
| State/province |
NY |
| ZIP/Postal code |
10029 |
| Country |
USA |
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| Platforms (1) |
| GPL28836 |
Illumina NextSeq 500 (Chlorocebus sabaeus) |
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| Samples (1) |
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| Relations |
| BioProject |
PRJNA669833 |
| SRA |
SRP287611 |
