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Temsavir blocks the immunomodulatory activities of HIV-1 soluble gp120

2023· article· en· W4353060830 on OpenAlexafffund
Jonathan Richard, Jérémie Prévost, Catherine Bourassa, Nathalie Brassard, Marianne Boutin, Mehdi Benlarbi, Guillaume Goyette, Halima Medjahed, Gabrielle Gendron‐Lepage, Fleur Gaudette, Hung-Ching Chen, William D. Tolbert, Amos B. Smith, Marzena Pazgier, Mathieu Dubé, Walther Mothes, Daniel E. Kaufmann, Andrés Finzi

Bibliographic record

VenueCell chemical biology · 2023
Typearticle
Languageen
FieldImmunology and Microbiology
TopicHIV Research and Treatment
Canadian institutionsUniversité du Québec à MontréalUniversité de MontréalCentre Hospitalier de l’Université de Montréal
FundersNational Institute of Allergy and Infectious DiseasesNational Institute of General Medical SciencesFonds de Recherche du Québec - SantéInstitute of Infection and ImmunityCanadian Institutes of Health ResearchNational Institutes of HealthCanada Research ChairsCanada Foundation for InnovationViiV Healthcare
KeywordsAntibody-dependent cell-mediated cytotoxicityAntigenicityGlycoproteinBystander effectImmune systemGp41Cell biologyDownregulation and upregulationAntibodyCytokineViral envelopeChemistryBiologyImmunologyEpitopeBiochemistryMonoclonal antibody

Abstract

fetched live from OpenAlex

While HIV-1-mediated CD4 downregulation protects infected cells from antibody-dependent cellular cytotoxicity (ADCC), shed gp120 binds to CD4 on uninfected bystander CD4 + T cells, sensitizing them to ADCC mediated by HIV + plasma. Soluble gp120-CD4 interaction on multiple immune cells also triggers a cytokine burst. The small molecule temsavir acts as an HIV-1 attachment inhibitor by preventing envelope glycoprotein (Env)-CD4 interaction and alters the overall antigenicity of Env by affecting its processing and glycosylation. Here we show that temsavir also blocks the immunomodulatory activities of shed gp120. Temsavir prevents shed gp120 from interacting with uninfected bystander CD4 + cells, protecting them from ADCC responses and preventing a cytokine burst. Mechanistically, this depends on temsavir's capacity to prevent soluble gp120-CD4 interaction, to reduce gp120 shedding, and to alter gp120 antigenicity. This suggests that the clinical benefits provided by temsavir could extend beyond blocking viral entry.

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: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.053
Threshold uncertainty score0.998

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 studies0.0000.001
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0010.003

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 head0.015
GPT teacher head0.249
Teacher spread0.234 · 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

Citations30
Published2023
Admission routes2
Has abstractyes

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