Differential Regulation of CXCR4 and CCR5 Expression by Interleukin (IL)-4 and IL-13 Is Associated with Inhibition of Chemotaxis and Human Immunodeficiency Virus (HIV) Type 1 Replication But Not HIV Entry into Human Monocytes
Bibliographic record
Abstract
Chemokine receptors CXCR4 and CCR5 play a key role in Human Immunodeficiency Virus (HIV) entry into CD4+ monocytic cells. Alteration in the expression levels of these receptors by immunoregulatory cytokines may influence viral entry and hence susceptibility to HIV infection, viral tropism, and disease progression. Helper T cell type 2 (Th2) cytokines interleukin (IL)-4 and IL-13, which share a subunit of their receptor components and exhibit similar biological effects, have been shown to play a key role in HIV infection and disease progression. In this study, we investigated the effects of IL-4 and IL-13 on the expression of CXCR4 and CCR5, and the biological implications of alteration of CXCR4 and CCR5 regulation on monocytic cells with respect to their migration in response to chemokines, HIV entry, and its replication. The results suggest that both IL-4 and IL-13 inhibited the expression of CXCR4, in contrast to CCR5, which was inhibited by IL-13 alone. The downregulation of CXCR4 and CCR5 was correspondingly associated with the inhibition of their respective ligand-induced chemotaxis. Although IL-13 inhibited the expression of both CXCR4 and CCR5, this downregulation of chemokine receptor expression was not sufficient to prevent virus entry. Furthermore, both IL-4 and IL-13 inhibited viral replication in monocytic cells, suggesting that inhibition of chemokine receptor expression per se by these cytokines may not be sufficient to prevent virus entry, and indicating these cytokines may be inhibiting viral replication by targeting pathways subsequent to virus entry.
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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 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".