Type I interferon responses are impaired in latently HIV infected cells
Bibliographic record
Abstract
BACKGROUND: The latent HIV-1 reservoir represents the primary barrier to the eradication of HIV-1 infection. The design of novel reservoir-clearance strategies, however, is impeded in part by the inability to distinguish latently HIV-infected cells from uninfected cells. Significant impairment of the type I interferon (IFN-I) response is observed during productive HIV-1 infection. Although this remains poorly described in the context of latent HIV-1 infection, presence of potential defects may serve as a novel therapeutic target. Therefore, IFN-I pathways were characterized using two latently HIV-1-infected cell lines, U1 and OM10.1, in comparison to their respective uninfected parental U937 and HL60 cell lines. FINDINGS: Constitutive expression and induction of important mediators of IFN-I signaling including IFNα/β cytokines, IFNAR1, MHC-I, ISG15, and PKR were evaluated following exogenous IFNα or poly(I:C) treatment. Differences in basal expression of IFNAR1, MHC-I, and PKR were observed between the latently HIV-1 infected and uninfected cell lines. In parallel, significant impairments in the induction of MHC-I, ISG15 and PKR, as well as secretion of IFNα/β cytokines were observed in response to appropriate exogenous stimulation within the two latently HIV-infected U1 and OM10.1 cells, relative to their HIV-uninfected parental cells. CONCLUSIONS: In comparison to the HIV-uninfected U937 and HL60 cell lines, widespread defects in IFN-I responsiveness were observed within the latently HIV-infected U1 and OM10.1 cells. These impairments represent novel therapeutic targets, which may be amenable to strategies currently employed in cancer therapy.
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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 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 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".