HIV-1 Nef Inhibits Lipopolysaccharide-induced IL-12p40 Expression by Inhibiting JNK-activated NFκB in Human Monocytic Cells
Post-publication record
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Bibliographic record
Abstract
Impaired cellular immunity caused by decreased production of Th1-type cytokines, including interleukin-12 (IL-12) is a major feature of HIV-1-associated immunodeficiency and acquired immunodeficiency syndrome. 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 lipopolysaccharide (LPS)-induced IL-12p40 production in monocytic cells is regulated by NFkappaB and AP-1 transcription factors through the activation of two distinct upstream signaling pathways, namely the c-Jun-N-terminal kinase (JNK) and the calmodulin-dependent protein kinase-II-activated pathways. Herein, we show that intracellular nef expressed through transduction of primary monocytes and promonocytic THP-1 cells with retroviral-mediated nef gene inhibited LPS-induced IL-12p40 transcription by inhibiting the JNK mitogen-activated protein kinases without affecting the calmodulin-dependent protein kinase-II-activated pathway. In addition, nef inhibited JNK-activated NFkappaB 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 NFkappaB activity.
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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".