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Record W4206984086 · doi:10.1101/2022.01.19.476693

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

2022· preprint· en· W4206984086 on OpenAlexafffund
Jung‐Hyun Choi, Xu Zhang, Christine Zhang, David L. Dai, Jun Luo, Reese Jalal Ladak, Qian Li, Shane Wiebe, Alex C.H. Liu, Xiaozhuo Ran, Jiaqi Yang, Parisa Naeli, Aitor Garzia, Lele Zhou, Niaz Mahmood, Qiyun Deng, Mohamed Elaish, Rongtuan Lin, 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

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2022
Typepreprint
Languageen
FieldImmunology and Microbiology
Topicinterferon and immune responses
Canadian institutionsUniversity of OttawaUniversity of AlbertaUniversity of ManitobaPrincess Margaret Cancer CentreUniversity of TorontoUniversity Health NetworkChildren's Hospital of Eastern OntarioChristie (Canada)McGill University
FundersBiotechnology and Biological Sciences Research CouncilCanadian Institutes of Health ResearchChina Scholarship CouncilDirectorate for Biological SciencesTerry Fox Research InstituteNational Research Foundation of KoreaQueen's UniversityNational Research Foundation
KeywordsMessenger RNATranslation (biology)Innate immune systemInterferonPsychological repressionBiologyCell biologyImmune systemProtein biosynthesismicroRNAVirologyRNAMechanism (biology)ImmunologyGene expressionMolecular biologyGeneGenetics

Abstract

fetched live from OpenAlex

Abstract 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 novel mechanism by which the SARS-CoV-2 virus co-opts an intrinsic cellular machinery to suppress the production of the key immunostimulatory cytokine IFN-β. We reveal that the SARS-CoV-2 encoded Non-Structural 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, leading to reduced viral infection. Our findings reveal a new 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 machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation 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 score0.002
Threshold uncertainty score0.006

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
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 science0.0000.000
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0020.001

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 head0.029
GPT teacher head0.261
Teacher spread0.232 · 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 source (direct Gemma or distilled Codex), 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

Citations5
Published2022
Admission routes2
Has abstractyes

Explore more

Same venuebioRxiv (Cold Spring Harbor Laboratory)Same topicinterferon and immune responsesFrench-language works237,207