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Record W2978699383 · doi:10.1128/jvi.00969-19

Differentiation into an Effector Memory Phenotype Potentiates HIV-1 Latency Reversal in CD4<sup>+</sup>T Cells

2019· article· en· W2978699383 on OpenAlexaff
Deanna A. Kulpa, Aarthi Talla, Jessica H. Brehm, Susan Pereira Ribeiro, Anne-Gaelle Bebin-Blackwell, Michael D. Miller, Richard Barnard, Steven G. Deeks, Daria J. Hazuda, Nicolas Chomont, Rafick‐Pierre Sékaly

Bibliographic record

VenueJournal of Virology · 2019
Typearticle
Languageen
FieldImmunology and Microbiology
TopicHIV Research and Treatment
Canadian institutionsUniversité de MontréalCentre Hospitalier de l’Université de Montréal
FundersNational Institute of Allergy and Infectious DiseasesNational Institutes of HealthMerck
KeywordsBiologyEffectorLatency (audio)PhenotypeDownregulation and upregulationCell biologyIn vitroVirus latencyGeneCellEx vivoImmunologyGeneticsCell cultureViral replication

Abstract

fetched live from OpenAlex

By performing phenotypic analysis of latency reversal in CD4 + T cells from virally suppressed individuals, we identify the T EM subset as the largest contributor to the inducible HIV reservoir. Differential responses of memory CD4 + T cell subsets to latency-reversing agents (LRAs) demonstrate that HIV gene expression is associated with heightened expression of transcriptional pathways associated with differentiation, acquisition of effector function, and cell cycle entry. In vitro modeling of the latent HIV reservoir in memory CD4 + T cell subsets identify LRAs that reverse latency with ranges of efficiency and specificity. We found that therapeutic induction of latency reversal is associated with upregulation of identical sets of T EM -associated genes and cell surface markers shown to be associated with latency reversal in our ex vivo and in vitro models. Together, these data support the idea that the effector memory phenotype supports HIV latency reversal in CD4 + T cells.

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 categoriesInsufficient payload (model declined to judge)
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.723
Threshold uncertainty score0.999

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)0.0020.003

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 head0.006
GPT teacher head0.233
Teacher spread0.227 · 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; both teacher heads agree on what is shown here.

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

Citations86
Published2019
Admission routes1
Has abstractyes

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