Intracellular HIV‐Nef Downregulates LPS‐induced IL‐12p40 Expression by Inhibiting JNK‐activated NFkB in Human Monocytic Cells
Bibliographic record
Abstract
Impaired cellular immunity caused by decreased production of Th1 type cytokines including IL‐12 is a major feature of HIV‐associated immunodeficiency and AIDS. IL‐12p40, an inducible subunit shared between IL‐12 and IL‐23, plays a critical role in the development of cellular immunity and its production is significantly decreased during HIV infection. The mechanism by which HIV induces loss of IL‐12p40 production remains poorly understood. We have previously shown that LPS‐induced IL‐12p40 production in monocytic cells is regulated by NFκB and AP‐1 through the activation of JNK and CaMK‐II. Herein, we show that intracellular Nef expressed through transduction of monocytic cells with retroviral‐mediated Nef gene inhibited LPS‐induced IL‐12p40 transcription by selectively inhibiting the JNK pathway without affecting the CaMK‐II‐activated pathway. In addition, Nef inhibited JNK‐activated NFκB without affecting the AP‐1 activity. Overall, our results suggest for the first time that intracellular Nef inhibited LPS‐activated JNK which may cause inhibition of IL‐12p40 expression in human monocytic cells by selectively inhibiting NFκB without affecting the CaMK‐II‐activated pathway. Furthermore, the inhibitory effect of Nef on JNK may have broad implications with respect to the inhibition of Th1 responses. The research was supported by NSERC, OGS, CIHR, and OHTN, Canada.
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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) | 0.001 | 0.000 |
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".