Isolation of a human betaretrovirus resembling mouse mammary tumor virus (MMTV) from patients with primary biliary cirrhosis
Bibliographic record
Abstract
A human betaretrovirus resembling the MMTV has been cloned from biliary epithelial cells and perihepatic lymph nodes of patients with primary biliary cirrhosis (PBC) [ 1 ]. The human betaretrovirus can trigger a PBC specific phenotype in vitro and antiviral therapy improves both biochemical and histological disease in patients with PBC. The human betaretrovirus can be detected in perihepatic lymph nodes in 75% of PBC patients by immunochemistry and RT-PCR [ 1 ]. Our goal was to provide proof that a human betaretrovirus infects patients by isolating the human betaretrovirus and detecting viral integration sites. DNA from livers, biliary epithelium and lymph nodes was used to identify proviral integration sites using linker mediated PCR. PBC peri-hepatic lymph node homogenates were co-cultured with Hs578T cells and infected cells were subcloned, clonally expanded and tested for betaretrovirus infection. Betaretrovirus was detected by RT-PCR in 16 supernatants from 28 subcloned Hs578T co-cultured cells. Betaretrovirus particles were identified by electron microscopy and 17 Integration sites were identified in infected Hs578T cells. 47 integration sites were identified from patients' samples. In patients with PBC, 1 or 2 integration sites were detected in 4 of 5 PBC biliary epithelial samples, 1 of 3 liver samples and 1 to 14 integration sites (median 5) were found in 7 of 10 PBC lymph nodes. Of note, the human betaretrovirus preferentially integrated within genes in 61% samples. Clustering of 3 or more sites within 15,000 Kb was observed on chromosomes 4, 5, 6, 8 and 11. The unequivocal detection of viral integration sites in the human genome and viral isolation studies provide proof that patients with PBC have infection with a transmissible betaretrovirus. Most PBC patients have evidence of betaretrovirus infection in biliary epithelial cells targeted by the disease process, whereas the perihepatic lymph nodes have the highest viral burden.
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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 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 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 | 0.000 |
| 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".