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Record W4213279127 · doi:10.1101/2022.02.21.481308

HIV-1 Vpu restricts Fc-mediated effector functions in vivo

2022· preprint· en· W4213279127 on OpenAlexafffund
Jérémie Prévost, Sai Priya Anand, Jyothi Krishnaswamy Rajashekar, Jonathan Richard, Guillaume Goyette, Halima Medjahed, Gabrielle Gendron‐Lepage, Hung-Ching Chen, Yaozong Chen, Joshua A. Horwitz, Michael W. Grunst, Susan Zolla‐Pazner, Barton F. Haynes, Dennis R. Burton, Richard A. Flavell, Frank Kirchhoff, Beatrice H. Hahn, Amos B. Smith, Marzena Pazgier, Michel C. Nussenzweig, Priti Kumar, Andrés Finzi

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2022
Typepreprint
Languageen
FieldImmunology and Microbiology
TopicHIV Research and Treatment
Canadian institutionsUniversité de MontréalMcGill UniversityCentre Hospitalier de l’Université de Montréal
FundersNational Institute of Diabetes and Digestive and Kidney DiseasesNational Institute of Allergy and Infectious DiseasesBaden-Württemberg StiftungCanadian Institutes of Health ResearchTulane UniversityFonds de Recherche du Québec - SantéUniversität zu KölnKarolinska InstitutetIsrael Science FoundationDeutsche ForschungsgemeinschaftBurnet InstituteNational Institutes of HealthInternational AIDS Vaccine Initiative
KeywordsAntibody-dependent cell-mediated cytotoxicityEffectorVirologyTetherinBiologyAntibodyGlycoproteinIn vivoVirusDownregulation and upregulationCell biologyViral envelopeImmunologyMolecular biologyGene

Abstract

fetched live from OpenAlex

SUMMARY Non-neutralizing antibodies (nnAbs) can eliminate HIV-1-infected cells via antibody-dependent cellular cytotoxicity (ADCC) and were identified as a correlate of protection in the RV144 vaccine trial. Fc-mediated effector functions of nnAbs were recently shown to alter the course of HIV-1 infection in vivo using a vpu -defective virus. Since Vpu is known to downregulate cell surface CD4, which triggers conformational changes in the viral envelope glycoprotein (Env), we ask whether the lack of Vpu expression was linked to the observed nnAbs activity. We found that restoring Vpu expression greatly reduces nnAb recognition of infected cells, rendering them resistant to ADCC responses. Moreover, administration of a nnAb in humanized mice reduces viral loads only in animals infected with a vpu -defective but not with a wildtype virus. Finally, nnAb Fc-effector functions are observed only on cells expressing Env in the “open” conformation. This work highlights the importance of Vpu-mediated evasion of humoral responses.

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 score0.002
Threshold uncertainty score0.008

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 integrity0.0000.001
Insufficient payload (model declined to judge)0.0020.001

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 head0.013
GPT teacher head0.228
Teacher spread0.215 · 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

Citations1
Published2022
Admission routes2
Has abstractyes

Explore more

Same venuebioRxiv (Cold Spring Harbor Laboratory)→Same topicHIV Research and Treatment→French-language works237,207→