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Record W3127173946 · doi:10.1126/sciadv.abe7386

Nsp1 protein of SARS-CoV-2 disrupts the mRNA export machinery to inhibit host gene expression

2021· article· en· W3127173946 on OpenAlexafffund
Ke Zhang, Lisa Miorin, Tadashi Makio, Ishmael Dehghan, Shengyan Gao, Yihu Xie, Hualin Zhong, Matthew A. Esparza, Thomas Kehrer, Tom C. Hobman, Christopher P. Ptak, Boning Gao, John D. Minna, Zhijian J. Chen, Adolfo García‐Sastre, Yi Ren, Richard W. Wozniak, Beatriz M. A. Fontoura

Bibliographic record

VenueScience Advances · 2021
Typearticle
Languageen
FieldMedicine
TopicViral Infections and Immunology Research
Canadian institutionsUniversity of Alberta
FundersDefense Sciences Office, DARPANational Institute of General Medical SciencesNational Cancer InstituteNational Institute of Allergy and Infectious DiseasesCanadian Institutes of Health ResearchCancer Prevention and Research Institute of Texas
KeywordsMessenger RNAGeneGene expressionHost (biology)Cell biologySevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2)BiologyVirologyCoronavirus disease 2019 (COVID-19)Molecular biologyGeneticsMedicine

Abstract

fetched live from OpenAlex

The ongoing unprecedented severe acute respiratory syndrome caused by the SARS-CoV-2 outbreak worldwide has highlighted the need for understanding viral-host interactions involved in mechanisms of virulence. Here, we show that the virulence factor Nsp1 protein of SARS-CoV-2 interacts with the host messenger RNA (mRNA) export receptor heterodimer NXF1-NXT1, which is responsible for nuclear export of cellular mRNAs. Nsp1 prevents proper binding of NXF1 to mRNA export adaptors and NXF1 docking at the nuclear pore complex. As a result, a significant number of cellular mRNAs are retained in the nucleus during infection. Increased levels of NXF1 rescues the Nsp1-mediated mRNA export block and inhibits SARS-CoV-2 infection. Thus, antagonizing the Nsp1 inhibitory function on mRNA export may represent a strategy to restoring proper antiviral host gene expression in infected cells.

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 score0.001
Threshold uncertainty score0.004

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 integrity0.0000.000
Insufficient payload (model declined to judge)0.0010.000

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 head0.038
GPT teacher head0.377
Teacher spread0.339 · 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

Citations228
Published2021
Admission routes2
Has abstractyes

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Same venueScience AdvancesSame topicViral Infections and Immunology ResearchFrench-language works237,207