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Record W4405355687 · doi:10.1016/j.isci.2024.111599

Dengue virus and Zika virus alter endoplasmic reticulum-mitochondria contact sites to regulate respiration and apoptosis

2024· article· en· W4405355687 on OpenAlex
Wesley Freppel, Viviana Andrea Barragan Torres, Olus Uyar, Anaïs Anton, Zaynab Nouhi, Mathilde Broquière, Clément Mazeaud, Aïssatou Aïcha Sow, Alexanne Léveillé, Claudia Gilbert, Nicolas Tremblay, Jonathan E Owen, Cheyanne L Bemis, Xavier Laulhé, Alain Lamarre, Christopher J. Neufeldt, Ian Gaël Rodrigue‐Gervais, Andreas Pichlmair, Denis Girard, Pietro Scaturro, Laura Hulea, Laurent Chatel‐Chaix

Why this work is in the frame

A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.

affAt least one author lists a Canadian institution in the pinned OpenAlex snapshot.
fundA Canadian funder is recorded on the work.

Bibliographic record

VenueiScience · 2024
Typearticle
Languageen
FieldMedicine
TopicMosquito-borne diseases and control
Canadian institutionsUniversité du QuébecFonds de Recherche du Québec - SantéUniversité de MontréalHôpital Maisonneuve-RosemontInstitut National de la Recherche Scientifique
FundersCanadian Institutes of Health ResearchTerry Fox FoundationBundesministerium für Bildung und ForschungNational Institute of Allergy and Infectious DiseasesCancer Research SocietyUniversität HeidelbergHelmholtz AssociationCanada Foundation for InnovationEuropean Research CouncilFonds de Recherche du Québec - SantéFondation du cancer du sein du QuébecInstitut national de la recherche scientifiqueDeutsche ForschungsgemeinschaftFondation familiale TrottierUniversity of AlbertaFonds de recherche du Québec – Nature et technologiesArmand-Frappier FoundationUniversité de MontréalUniversity of SaskatchewanMcGill UniversityCentre d’Excellence en Recherche sur les Maladies Orphelines – Fondation CourtoisAix-Marseille Université
KeywordsEndoplasmic reticulumDengue virusMitochondrionCell biologyApoptosisZika virusVirologyDengue feverVirusChemistryBiologyBiochemistry

Abstract

fetched live from OpenAlex

During infection, dengue virus (DENV) and Zika virus (ZIKV), two (ortho)flaviviruses of public health concern worldwide, induce alterations of mitochondria morphology to favor viral replication, suggesting a viral co-opting of mitochondria functions. Here, we performed an extensive transmission electron microscopy-based quantitative analysis to demonstrate that both DENV and ZIKV alter endoplasmic reticulum-mitochondria contact sites (ERMC). This correlated at the molecular level with an impairment of ERMC tethering protein complexes located at the surface of both organelles. Furthermore, virus infection modulated the mitochondrial oxygen consumption rate. Consistently, metabolomic and mitoproteomic analyses revealed a decrease in the abundance of several metabolites of the Krebs cycle and changes in the stoichiometry of the electron transport chain. Most importantly, ERMC destabilization by protein knockdown increased virus replication while dampening ZIKV-induced apoptosis. Overall, our results support the notion that flaviviruses hijack ERMCs to generate a cytoplasmic environment beneficial for sustained and efficient 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.

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: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.235
Threshold uncertainty score0.442

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 head0.013
GPT teacher head0.277
Teacher spread0.265 · 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