Hepatitis C virus core protein reduces <scp>CD</scp>8<sup>+</sup> T‐cell proliferation, perforin production and degranulation but increases <scp>STAT</scp>5 activation
Bibliographic record
Abstract
Summary Clearance of hepatitis C virus (HCV) is dependent on an effective virus‐specific CD8+ T‐cell response, which is dysfunctional in chronic HCV infection. Dysfunction in bulk or non‐HCV‐specific CD8+ T‐cells in HCV infection has also been observed. This may contribute to observed reductions in immunity to other diseases (e.g. cancer, viral co‐infections) in HCV‐infected individuals. Evidence suggests that the HCV core protein (found in blood as free protein) may contribute to this impairment. To determine if HCV core contributes to the impairment of effector functions and survival potential of CD8+ T‐cells, isolated human CD8+ T‐cells from healthy donors were pre‐incubated with recombinant HCV core protein for 72 hr and then stimulated in vitro to evaluate proliferation, survival potential and effector functions. Pre‐incubation of stimulated CD8+ T‐cells with HCV core significantly reduced their proliferation. Perforin production and degranulation were also decreased, but interferon‐γ production was unchanged. Additionally, when CD8+ T‐cells were treated with serum from HCV+ individuals, they produced less perforin than cells treated with healthy serum. Up‐regulation of anti‐apoptotic Bcl‐2 was slightly lower in cells treated with HCV core, but signal transducer and activator of transcription 5 (STAT5) activation was increased, suggesting dysregulation downstream of STAT activation. Our study reveals that HCV core reduces the activity and target lysis‐associated functions of CD8+ T‐cells. This may contribute to the generalized impairment of CD8+ T‐cells observed in HCV infection. These findings provide insight for the design of novel counteractive immune‐mediated strategies including the design of effective therapeutic vaccines for use in HCV+ individuals.
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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 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 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".