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Record W4306895319 · doi:10.1126/science.abn9884

Structure of the hepatitis C virus E1E2 glycoprotein complex

2022· article· en· W4306895319 on OpenAlexafffund
Alba Torrents de la Peña, Kwinten Sliepen, Lisa Eshun-Wilson, Maddy L. Newby, Joel D. Allen, Ian Zon, Sylvie M. Koekkoek, Ana Chumbe, Max Crispin, Janke Schinkel, Gabriel C. Lander, Rogier W. Sanders, Andrew B. Ward

Bibliographic record

VenueScience · 2022
Typearticle
Languageen
FieldMedicine
TopicHepatitis C virus research
Canadian institutionsInstitute of Infection and Immunity
FundersInstitute of Infection and ImmunityNational Institute of General Medical SciencesNederlandse Organisatie voor Wetenschappelijk OnderzoekBill and Melinda Gates FoundationNational Institutes of HealthNational Science Foundation
KeywordsVirologyGlycoproteinEpitopeNeutralizing antibodyHepatocellular carcinomaHepatitis C virusAntibodyViral entryRational designViral envelopeCD81VirusBiologyCapsidChemistryImmunologyViral replicationCancer researchBiochemistryGenetics

Abstract

fetched live from OpenAlex

Hepatitis C virus (HCV) infection is a leading cause of chronic liver disease, cirrhosis, and hepatocellular carcinoma in humans and afflicts more than 58 million people worldwide. The HCV envelope E1 and E2 glycoproteins are essential for viral entry and comprise the primary antigenic target for neutralizing antibody responses. The molecular mechanisms of E1E2 assembly, as well as how the E1E2 heterodimer binds broadly neutralizing antibodies, remain elusive. Here, we present the cryo-electron microscopy structure of the membrane-extracted full-length E1E2 heterodimer in complex with three broadly neutralizing antibodies-AR4A, AT1209, and IGH505-at ~3.5-angstrom resolution. We resolve the interface between the E1 and E2 ectodomains and deliver a blueprint for the rational design of vaccine immunogens and antiviral drugs.

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 categoriesInsufficient payload (model declined to judge)
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 score0.635
Threshold uncertainty score0.997

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.001
Science and technology studies0.0000.001
Scholarly communication0.0000.000
Open science0.0010.001
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0040.000

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 head0.033
GPT teacher head0.325
Teacher spread0.292 · 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.

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

Citations89
Published2022
Admission routes2
Has abstractyes

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