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Record W4393254619 · doi:10.1038/s41564-024-01672-3

Crimean–Congo haemorrhagic fever virus uses LDLR to bind and enter host cells

2024· article· en· W4393254619 on OpenAlexaff
Vanessa Monteil, Shane C. Wright, Matheus Dyczynski, Max J. Kellner, Sofia Appelberg, Sebastian Platzer, Ahmed Ibrahim, Hyesoo Kwon, Ioannis Pittarokoilis, Mattia Mirandola, Georg Michlits, Stéphanie Devignot, Elizabeth Elder, Samir Abdurahman, Sándor Bereczky, Binnur Bağcı, Sonia Youhanna, Teodor Aastrup, Volker M. Lauschke, Cristiano Salata, Nazif Elaldı, Friedemann Weber, Nuria Monserrat, David W. Hawman, Heinz Feldmann, Moritz Horn, Josef Penninger, Alì Mirazimi

Bibliographic record

VenueNature Microbiology · 2024
Typearticle
Languageen
FieldMedicine
TopicViral Infections and Vectors
Canadian institutionsUniversity of British Columbia
FundersHorizon 2020 Framework ProgrammeNational Institutes of HealthVetenskapsrådetSvenska Sällskapet för Medicinsk ForskningUniversità degli Studi di PadovaKarolinska InstitutetDivision of Intramural Research, National Institute of Allergy and Infectious DiseasesEuropean CommissionTexas Biomedical Research Institute
KeywordsLDL receptorVirologyBiologyGlycoproteinVirusAntibodyPopulationReceptorLipoproteinImmunologyMolecular biologyMedicineCholesterolGeneticsBiochemistry

Abstract

fetched live from OpenAlex

Climate change and population densities accelerated transmission of highly pathogenic viruses to humans, including the Crimean-Congo haemorrhagic fever virus (CCHFV). Here we report that the Low Density Lipoprotein Receptor (LDLR) is a critical receptor for CCHFV cell entry, playing a vital role in CCHFV infection in cell culture and blood vessel organoids. The interaction between CCHFV and LDLR is highly specific, with other members of the LDLR protein family failing to bind to or neutralize the virus. Biosensor experiments demonstrate that LDLR specifically binds the surface glycoproteins of CCHFV. Importantly, mice lacking LDLR exhibit a delay in CCHFV-induced disease. Furthermore, we identified the presence of Apolipoprotein E (ApoE) on CCHFV particles. Our findings highlight the essential role of LDLR in CCHFV infection, irrespective of ApoE presence, when the virus is produced in tick cells. This discovery holds profound implications for the development of future therapies against CCHFV.

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 score0.638
Threshold uncertainty score0.684

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 integrity0.0000.001
Insufficient payload (model declined to judge)0.0010.001

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 head0.008
GPT teacher head0.286
Teacher spread0.278 · 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

Citations48
Published2024
Admission routes1
Has abstractyes

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