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Record W4287838589 · doi:10.1073/pnas.2204539119

SARS-CoV-2 impairs interferon production via NSP2-induced repression of mRNA translation

2022· article· en· W4287838589 on OpenAlexafffund
Xu Zhang, Jung‐Hyun Choi, David L. Dai, Jun Luo, Reese Jalal Ladak, Qian Li, Yimeng Wang, Christine Zhang, Shane Wiebe, Alex C.H. Liu, Xiaozhuo Ran, Jiaqi Yang, Parisa Naeli, Aitor Garzia, Lele Zhou, Niaz Mahmood, Qiyun Deng, Mohamed Elaish, Rongtuan Lin, Lara K. Mahal, Tom C. Hobman, Jerry Pelletier, Tommy Alain, Silvia M. Vidal, Thomas F. Duchaîne, Mohammad T. Mazhab‐Jafari, Xiaojuan Mao, Seyed Mehdi Jafarnejad, Nahum Sonenberg

Bibliographic record

VenueProceedings of the National Academy of Sciences · 2022
Typearticle
Languageen
FieldImmunology and Microbiology
Topicinterferon and immune responses
Canadian institutionsMcGill Genome CentreUniversity of OttawaUniversity of AlbertaChildren's Hospital of Eastern OntarioMcGill UniversityChristie (Canada)University of ManitobaPrincess Margaret Cancer CentreUniversity of TorontoUniversity Health Network
FundersBiotechnology and Biological Sciences Research CouncilNatural Sciences and Engineering Research Council of CanadaCanadian Institutes of Health ResearchChina Scholarship CouncilQueen's UniversityDirectorate for Biological SciencesTerry Fox Research InstituteNational Research Foundation of KoreaCanada Excellence Research Chairs, Government of CanadaUK Research and InnovationNational Research FoundationQueen's University BelfastGovernment of CanadaPrincess Margaret Cancer Foundation
KeywordsInnate immune systemMessenger RNATranslation (biology)InterferonBiologyCell biologyPsychological repressionImmune systemVirologyRNAProtein biosynthesismicroRNAViral replicationMechanism (biology)CytokineVirusImmunologyGene expressionMolecular biologyGeneGenetics

Abstract

fetched live from OpenAlex

Viruses evade the innate immune response by suppressing the production or activity of cytokines such as type I interferons (IFNs). Here we report the discovery of a mechanism by which the SARS-CoV-2 virus coopts an intrinsic cellular machinery to suppress the production of the key immunostimulatory cytokine IFN-β. We reveal that the SARS-CoV-2 encoded nonstructural protein 2 (NSP2) directly interacts with the cellular GIGYF2 protein. This interaction enhances the binding of GIGYF2 to the mRNA cap-binding protein 4EHP, thereby repressing the translation of the Ifnb1 mRNA. Depletion of GIGYF2 or 4EHP significantly enhances IFN-β production, which inhibits SARS-CoV-2 replication. Our findings reveal a target for rescuing the antiviral innate immune response to SARS-CoV-2 and other RNA viruses.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.004
Threshold uncertainty score0.249

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0010.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.066
GPT teacher head0.325
Teacher spread0.258 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations85
Published2022
Admission routes2
Has abstractyes

Explore more

Same venueProceedings of the National Academy of SciencesSame topicinterferon and immune responsesFrench-language works237,207