Augmented hepatic interferon gamma expression and T-cell influx characterize acute hepatitis progressing to recovery and residual lifelong virus persistence in experimental adult woodchuck hepatitis virus infection
Bibliographic record
Abstract
Woodchucks infected with woodchuck hepatitis virus (WHV) have profiles of liver disease and age-dependent rates of progression to chronic hepatitis (CH) comparable with those seen in human hepatitis B. The mechanism of recovery from acute hepadnaviral infection or its evolution to chronicity remains unknown, although the liver immune responses are expected to play an important role. To determine the dynamics of intrahepatic cytokine expression and T-cell involvement, and to assess their value in predicting the outcome of acute hepatitis (AH) in the adult onset of WHV infection, we evaluated liver transcription of interferon gamma (IFN-gamma); tumor necrosis factor alpha (TNF-alpha); interleukins (IL)-2, -4, and -6; and the T-cell influx in relation to disease histologic severity and virus load in serial liver biopsies collected during the life span of experimentally infected woodchucks. Our results show that recovery from viral AH in adulthood is preceded by a significantly greater hepatic expression of IFN-gamma and CD3, an increased TNF-alpha transcription, lower hepatic WHV load, and a greater degree of liver inflammation than those in acute infection with CH outcome. Furthermore, we have learned that the elevated IFN-gamma, TNF-alpha, and CD3 expression in the liver endures for years not only in CH, but also, although to a lesser extent, in apparently completely resolved infection. This is consistent with our previous findings that residual WHV replication and remnant liver inflammation continue for life after recovery from AH. This study indicates that antiviral cytokines, in particular IFN-gamma, may play a central role in the long-term control of occult hepadnavirus persistence in the liver.
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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".