CBP/p300 lysine acetyltransferases inhibit HIV-1 expression in latently infected T cells
Bibliographic record
Abstract
HIV-1 latency is regulated by chromatin modifying enzymes, and histone deacetylase inhibitors (HDACi) cause reactivation of provirus expression. Surprisingly, we observed that inhibitors of the CBP/p300 acetyltransferases also cause reversal of latency in T cells. CBP/p300 inhibitors synergize with various latency reversing agents to cause HIV-1 reactivation. In contrast, inhibition of CBP/p300 impaired reversal of latency by the HDACi SAHA, indicating that CBP/p300 must contribute to acetylation on the HIV-1 LTR associated with HDACi-mediated latency reversal. CBP/p300 inhibition caused loss of H3K27ac and H3K4me3 from the LTR, but did not affect association of the inhibitor protein BRD4. Furthermore, inhibition of the additional lysine acetyltransferases PCAF/GCN5 or KAT6A/KAT6B also caused reversal of latency, suggesting that protein acetylation has an inhibitory effect on HIV-1 expression. Collectively, these observations indicate that transcription from the HIV-1 LTR is controlled both positively and negatively by protein acetylation, likely including both histone and non-histone regulatory targets.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot 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.
Codex and Gemma teacher scores by category
| 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 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.005 |
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; both teacher heads agree on what is shown here.
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".