Acquisition of Host-Derived CD40L by HIV-1<i>In Vivo</i>and Its Functional Consequences in the B-Cell Compartment
Bibliographic record
Abstract
Aberrant activation of the B-cell compartment and hypergammaglobulinemia were among the first recognized characteristics of HIV-1-infected patients in the early 1980s. It has been demonstrated previously that HIV-1 particles acquire the costimulatory molecule CD40L when budding from activated CD4(+) T cells. In this paper, we confirmed first that CD40L-bearing virions are detected in the plasma from untreated HIV-1-infected individuals. To define the biological functions of virus-associated CD40L and fully characterize its influence on the activation state of B cells, we conducted a large-scale gene expression analysis using microarray technology on B cells isolated from human tonsillar tissue. Comparative analyses of gene expression profiles revealed that CD40L-bearing virions induce a highly similar response to the one observed in samples treated with a CD40 agonist, indicating that virions bearing CD40L can efficiently activate B cells. Among modulated genes, many cytokines/chemokines (CCL17, CCL22), surface molecules (CD23, CD80, ICAM-1), members of the TNF superfamily (FAS, A20, TNIP1, CD40, lymphotoxin alpha, lymphotoxin beta), transcription factors and associated proteins (NFKB1, NFKBIA, NFKBIE), second messengers involved in CD40 signaling (TRAF1, TRAF3, MAP2K1, phosphatidylinositol 3-kinase), and the activation-induced cytidine deaminase (AID) were identified. Moreover, we show that soluble factors induced upon the exposure of B cells to CD40L-bearing virions can exert chemoattractant properties toward CD4(+) T cells. We thus propose that a positive feedback loop involving CD40L-bearing HIV-1 particles issued from CD4(+) T cells productively infected with HIV-1 play a role in the virus-induced dysfunction of humoral immunity by chronically activating B cells through sustained CD40 signaling.
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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 | 0.001 | 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".