Induction of Prothrombinase fgl2 by the Nucleocapsid Protein of Virulent Mouse Hepatitis Virus Is Dependent on Host Hepatic Nuclear Factor-4α
Bibliographic record
Abstract
Fibrinogen-like protein 2/fibroleukin (Fgl2) plays a pivotal role in the pathogenesis of both experimental and human fulminant hepatic failure. We have reported recently that the nucleocapsid (N) protein from strains of murine hepatitis virus (MHV-3, MHV-A59), which cause massive hepatocellular necrosis but not from strains (MHV-JHM, MHV-2) which do not produce serious liver disease, induces transcription of fgl2. The purpose of the present study was to characterize both viral and host factor(s) necessary for viral induced transcription of fgl2. Mutation of residues Gly-12, Pro-38, Asn-40, Gln-41, and Asn-42 within domain 1 of the N protein of MHV-A59 to their corresponding residues found in MHV-2 abrogated fgl2 transcription, whereas mutation of other N protein domains, including a protein expressed from an internal reading frame (I protein), did not affect fgl2 gene transcription. We then examined the -372 to -306 sequence within the 1.3-kb fgl2 promoter region upstream from the transcription start site that was previously identified as necessary for N protein-induced gene transcription. We demonstrated that the -331/-325 HNF4 cis-element and its cognate transcription factor, HNF4alpha, are necessary for virus-induced fgl2 gene transcription. In uninfected macrophages and macrophages infected with MHV-2, an unidentified protein occupies the HNF4 cis-element. Following stimulation with MHV-A59, it was shown by electrophoretic mobility shift assay that HNF4alpha binds the HNF4 cis-element in the fgl2 promoter. We further report the unprecedented presence of HNF4alpha in peritoneal macrophages. Collectively, the results of this study define both viral and host factors necessary for induction of fgl2 prothrombinase gene transcription in MHV infection and may provide an explanation for the hepatotrophic nature of MHV-induced fulminant hepatic failure.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 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 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".