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 CD 8 + T‐cell response, which is dysfunctional in chronic HCV infection. Dysfunction in bulk or non‐ HCV ‐specific CD 8 + 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 CD 8 + T‐cells, isolated human CD 8 + 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 CD 8 + T‐cells with HCV core significantly reduced their proliferation. Perforin production and degranulation were also decreased, but interferon‐ γ production was unchanged. Additionally, when CD 8 + 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 ( STAT 5) activation was increased, suggesting dysregulation downstream of STAT activation. Our study reveals that HCV core reduces the activity and target lysis‐associated functions of CD 8 + T‐cells. This may contribute to the generalized impairment of CD 8 + 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 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 | 0.001 | 0.012 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| 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".