Upstream Stimulatory Factors regulate HIV-1 latency and are required for robust T cell activation
Bibliographic record
Abstract
Abstract RBF-2, composed minimally of the factors USF1, USF2, and TFII-I, is the cognate binding complex of stringently conserved cis -elements on the HIV-1 LTR, designated RBE3 and RBE1. Mutations of these elements prevent induction of provirus in response to T cell signaling. However, the function of USF1 and USF2 for this effect are relatively uncharacterized. Here, we find that deletion of the USF2 but not USF1 gene in T cells abrogates HIV-1 expression. Loss of USF2 caused a reduction in expression of USF1 protein, an effect that was not associated with decreased USF1 mRNA abundance. USF1 and USF2 were previously shown to exist predominately as heterodimers on DNA in vivo and cooperatively regulate target genes. To examine this, we performed RNA-seq analysis of T cell lines bearing knockouts of genes encoding these factors. In untreated cells we found limited evidence of coordinated global gene regulation between USF1 and USF2. In contrast we observed a high degree of genome-wide cooperative regulation of RNA expression between these factors in cells stimulated with the combination of PMA and ionomycin. In particular, we found that USF1 deletion resulted in a restricted T cell activation response, and this phenotype was exaggerated in USF2 knockout cells. These observations indicate that USF2, but not USF1, is crucial for HIV-1 expression, but the combined function of these factors is required for full T cell response.
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 imitationNot 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.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
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.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
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".