MétaCan
Menu
Back to cohort
Record W4400109975 · doi:10.1016/j.celrep.2024.114414

Retinoic acid enhances HIV-1 reverse transcription and transcription in macrophages via mTOR-modulated mechanisms

2024· article· en· W4400109975 on OpenAlexafffund
Jonathan Dias, Amélie Cattin, Maryam Bendoumou, Antoine Dutilleul, Robert Lodge, Jean-Philippe Goulet, Augustine Fert, Laurence Raymond Marchand, Tomas Raul Wiche Salinas, Christ-Dominique Ngassaki Yoka, Etiene Moreira Gabriel, Ramon Edwin Caballero, Jean-Pierre Routy, Éric A. Cohen, Carine Van Lint, Petronela Ancuța

Bibliographic record

VenueCell Reports · 2024
Typearticle
Languageen
FieldImmunology and Microbiology
TopicHIV Research and Treatment
Canadian institutionsMcGill University Health CentreMontreal Clinical Research InstituteUniversité de MontréalCentre Hospitalier de l’Université de Montréal
FundersNational Institute of Neurological Disorders and StrokeNational Institute of Allergy and Infectious DiseasesNational Institute on Drug AbuseNational Heart, Lung, and Blood InstituteFonds pour la Formation à la Recherche dans l’Industrie et dans l’AgricultureNational Institutes of HealthFonds de Recherche du Québec - SantéFonds De La Recherche Scientifique - FNRSUniversité LavalFonds de recherche du QuébecCanadian Institutes of Health ResearchInternational Association of SedimentologistsMcGill UniversityMcGill University Health CentreNational Institute of Diabetes and Digestive and Kidney DiseasesViiV HealthcareThomas Jefferson UniversityKoning BoudewijnstichtingFondation du CHUMCanadian Foundation for AIDS Research
KeywordsRetinoic acidSAMHD1BiologyTranscription (linguistics)PI3K/AKT/mTOR pathwayViral replicationCell biologyGene knockdownTranscription factorTranscriptomeRNA polymerase IIReverse transcriptaseVirologyRNAGene expressionGeneSignal transductionVirusGeneticsPromoter

Abstract

fetched live from OpenAlex

The intestinal environment facilitates HIV-1 infection via mechanisms involving the gut-homing vitamin A-derived retinoic acid (RA), which transcriptionally reprograms CD4 + T cells for increased HIV-1 replication/outgrowth. Consistently, colon-infiltrating CD4 + T cells carry replication-competent viral reservoirs in people with HIV-1 (PWH) receiving antiretroviral therapy (ART). Intriguingly, integrative infection in colon macrophages, a pool replenished by monocytes, represents a rare event in ART-treated PWH, thus questioning the effect of RA on macrophages. Here, we demonstrate that RA enhances R5 but not X4 HIV-1 replication in monocyte-derived macrophages (MDMs). RNA sequencing, gene set variation analysis, and HIV interactor NCBI database interrogation reveal RA-mediated transcriptional reprogramming associated with metabolic/inflammatory processes and HIV-1 resistance/dependency factors. Functional validations uncover post-entry mechanisms of RA action including SAMHD1-modulated reverse transcription and CDK9/RNA polymerase II (RNAPII)-dependent transcription under the control of mammalian target of rapamycin (mTOR). These results support a model in which macrophages residing in the intestine of ART-untreated PWH contribute to viral replication/dissemination in an mTOR-sensitive manner.

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 score0.001
Threshold uncertainty score0.005

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 integrity0.0000.000
Insufficient payload (model declined to judge)0.0010.000

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 head0.009
GPT teacher head0.232
Teacher spread0.223 · 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

Citations8
Published2024
Admission routes2
Has abstractyes

Explore more

Same venueCell ReportsSame topicHIV Research and TreatmentFrench-language works237,207