Parallel 33: HCV Pathogenesis: Is the Battle Over?
Bibliographic record
Abstract
ulate all steps of the HBV life cycle in metabolically competent adult hepatocytes has thus far hampered efforts to devise novel treatment strategies. Despite the recent description of NTCP as HBV receptor on hepatocytes, models relying on NTCP overexpression and non-polarized culture of hepatoma cells do not accurately reflect HBV infection. Here we describe a novel HBV primary cell culture model utilizing 3D microfluidic cell culture technology of human adult hepatocytes. Hepatocytes form a physiological liver microarchitecture, as determined by electron microscopy, including the formation of tight junctions and bile canaliculi. Longitudinal genomic, proteomic and functional cell assays confirm the ability to culture primary hepatocyte microtissues for at least 21 days without dedifferentiation or cell mortality. Persistent in vitro infection is established upon inoculation with Hepatitis B virus derived from primary patient isolates or recombinant sources, without requirement for pre-treatment of the cultures with cytotoxic solvents such as dimethyl sulfoxide. Accumulation of covalently closed circular (ccc)DNA, replication intermediates, pregenomic RNA as well as de novo production of significant titres of infectious virus progeny, as determined by HBsAg secretion and reinfection of nave cells, confirms that the complete HBV life cycle is supported in vitro. In addition to HBeAg-positive isolates, infection is successfully launched in liver microtissues using HBeAg-negative patient isolates, and viral replication is inhibited upon treatment with direct acting antiviral drugs. This HBV cell culture model offers a new means for conducting target validation, drug discovery and development of novel therapeutic candidates against HBV in a physiological hepatocyte background.
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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 | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.002 |
| Scholarly communication | 0.003 | 0.002 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.002 | 0.002 |
| Insufficient payload (model declined to judge) | 0.020 | 0.007 |
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".