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Record W3195526608 · doi:10.1371/journal.ppat.1009824

pUL21 is a viral phosphatase adaptor that promotes herpes simplex virus replication and spread

2021· article· en· W3195526608 on OpenAlexfundno aff
Tomasz H. Benedyk, Julia Muenzner, Viv Connor, Yue Han, Katherine A. Brown, Kaveesha J. Wijesinghe, Yunhui Zhuang, Susanna Colaco, Guido A. Stoll, Owen S. Tutt, Stanislava Svobodova, Dmitri I. Svergun, Neil A. Bryant, Janet E. Deane, Andrew E. Firth, Cy M. Jeffries, Colin M. Crump, Stephen C. Graham

Bibliographic record

VenuePLoS Pathogens · 2021
Typearticle
Languageen
FieldMedicine
TopicHerpesvirus Infections and Treatments
Canadian institutionsnot available
FundersBiotechnology and Biological Sciences Research CouncilDirectorate for Biological SciencesQueen's UniversityUniversity of BristolUniversity of GlasgowWellcome TrustUniversity of PennsylvaniaFrancis Crick InstituteNational Institute for Health and Care ResearchMedical Research CouncilRoyal SocietyWellcome
KeywordsHerpes simplex virusSignal transducing adaptor proteinBiologyViral replicationVirusVirologyDephosphorylationCell biologyProtein phosphatase 1PhosphataseSingle-stranded binding proteinPhosphorylationGeneticsDNA-binding proteinGeneTranscription factor

Abstract

fetched live from OpenAlex

The herpes simplex virus (HSV)-1 protein pUL21 is essential for efficient virus replication and dissemination. While pUL21 has been shown to promote multiple steps of virus assembly and spread, the molecular basis of its function remained unclear. Here we identify that pUL21 is a virus-encoded adaptor of protein phosphatase 1 (PP1). pUL21 directs the dephosphorylation of cellular and virus proteins, including components of the viral nuclear egress complex, and we define a conserved non-canonical linear motif in pUL21 that is essential for PP1 recruitment. In vitro evolution experiments reveal that pUL21 antagonises the activity of the virus-encoded kinase pUS3, with growth and spread of pUL21 PP1-binding mutant viruses being restored in adapted strains where pUS3 activity is disrupted. This study shows that virus-directed phosphatase activity is essential for efficient herpesvirus assembly and spread, highlighting the fine balance between kinase and phosphatase activity required for optimal virus replication.

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)0.000
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: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.778
Threshold uncertainty score0.621

Codex and Gemma teacher scores by category

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)0.0000.000

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 head0.044
GPT teacher head0.292
Teacher spread0.248 · 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

Citations36
Published2021
Admission routes1
Has abstractyes

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