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Record W2787737417 · doi:10.1101/242958

Chromatin Functional States Correlate with HIV Latency Reversal in Infected Primary CD4 <sup>+</sup> T cells

2018· preprint· en· W2787737417 on OpenAlexfundno aff
Emilie Battivelli, Matthew S. Dahabieh, Mohamed Abdel‐Mohsen, J. Peter Svensson, Israel Tojal da Silva, Lilian B. Cohn, Andrea Gramatica, Steven G. Deeks, Warner C. Greene, Satish K. Pillai, Eric Verdin

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2018
Typepreprint
Languageen
FieldImmunology and Microbiology
TopicHIV Research and Treatment
Canadian institutionsnot available
FundersNational Institute of Dental and Craniofacial ResearchNational Institute of Allergy and Infectious DiseasesCanadian Institutes of Health ResearchUniversity of California, San FranciscoCenter for AIDS Research, University of WashingtonNational Institutes of HealthVetenskapsrådetNational Institute on Drug AbuseCancerfondenCalifornia HIV/AIDS Research ProgramamfAR, The Foundation for AIDS Research
KeywordsProvirusChromatinVirologyBiologyLatency (audio)Human immunodeficiency virus (HIV)Virus latencyVirusImmunologyGenomeGeneticsViral replicationDNAGene

Abstract

fetched live from OpenAlex

ABSTRACT Human immunodeficiency virus (HIV) infection cannot be cured due to a small reservoir of latently infected CD4 + T cells in treated patients. The “shock and kill” approach proposes to eliminate the reservoir by inducing its activation and the direct or indirect killing of infected cells. Current latency reversing agents (LRAs) do not reduce the viral reservoir in treated patients. We use a novel dual-fluorescent HIV reporter to identify and purify latent cells, and to determine the fraction of latent cells that undergo viral reactivation after infection of primary CD4 + T cells. Unexpectedly, LRAs reactivate less than 5% of latent proviruses. Analysis of HIV integration sites from induced and non-induced latent populations reveals distinct provirus integration sites between these two populations in terms of chromatin functional states. These findings challenge “shock and kill”, and suggest the need of more potent LRAs in combination with immunomodulatory approaches to eradicate HIV reservoir.

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 score0.004
Threshold uncertainty score0.014

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)0.0040.001

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 head0.008
GPT teacher head0.196
Teacher spread0.188 · 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

Citations6
Published2018
Admission routes1
Has abstractyes

Explore more

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